Interventions for weight loss in people with chronic kidney disease who are overweight or obese

Abstract

Background

Obesity and chronic kidney disease (CKD) are highly prevalent worldwide and result in substantial health care costs. Obesity is a predictor of incident CKD and progression to kidney failure. Whether weight loss interventions are safe and effective to impact on disease progression and clinical outcomes, such as death remains unclear.

Objectives

This review aimed to evaluate the safety and efficacy of intentional weight loss interventions in overweight and obese adults with CKD; including those with end‐stage kidney disease (ESKD) being treated with dialysis, kidney transplantation, or supportive care.

Search methods

We searched the Cochrane Kidney and Transplant Register of Studies up to 14 December 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria

Randomised controlled trials (RCTs) and quasi‐RCTs of more than four weeks duration, reporting on intentional weight loss interventions, in individuals with any stage of CKD, designed to promote weight loss as one of their primary stated goals, in any health care setting.

Data collection and analysis

Two authors independently assessed study eligibility and extracted data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess the certainty of evidence. We estimated treatment effects using random‐effects meta‐analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised mean difference (SMD) for continuous outcomes or in descriptive format when meta‐analysis was not possible.

Main results

We included 17 RCTs enrolling 988 overweight or obese adults with CKD. The weight loss interventions and comparators across studies varied. We categorised comparisons into three groups: any weight loss intervention versus usual care or control; any weight loss intervention versus dietary intervention; and surgical intervention versus non‐surgical intervention. Methodological quality was varied, with many studies providing insufficient information to accurately judge the risk of bias. Death (any cause), cardiovascular events, successful kidney transplantation, nutritional status, cost effectiveness and economic analysis were not measured in any of the included studies. Across all 17 studies many clinical parameters, patient‐centred outcomes, and adverse events were not measured limiting comparisons for these outcomes.

In studies comparing any weight loss intervention to usual care or control, weight loss interventions may lead to weight loss or reduction in body weight post intervention (6 studies, 180 participants: MD ‐3.69 kg, 95% CI ‐5.82 to ‐1.57; follow‐up: 5 weeks to 12 months, very low‐certainty evidence). In very low certainty evidence any weight loss intervention had uncertain effects on body mass index (BMI) (4 studies, 100 participants: MD ‐2.18 kg/m², 95% CI ‐4.90 to 0.54), waist circumference (2 studies, 53 participants: MD 0.68 cm, 95% CI ‐7.6 to 6.24), proteinuria (4 studies, 84 participants: 0.29 g/day, 95% CI ‐0.76 to 0.18), systolic (4 studies, 139 participants: ‐3.45 mmHg, 95% CI ‐9.99 to 3.09) and diastolic blood pressure (4 studies, 139 participants: ‐2.02 mmHg, 95% CI ‐3.79 to 0.24). Any weight loss intervention made little or no difference to total cholesterol, high density lipoprotein cholesterol, and inflammation, but may lower low density lipoprotein cholesterol.

There was little or no difference between any weight loss interventions (lifestyle or pharmacological) compared to dietary‐only weight loss interventions for weight loss, BMI, waist circumference, proteinuria, and systolic blood pressure, however diastolic blood pressure was probably reduced. Furthermore, studies comparing the efficacy of different types of dietary interventions failed to find a specific dietary intervention to be superior for weight loss or a reduction in BMI.

Surgical interventions probably reduced body weight (1 study, 11 participants: MD ‐29.50 kg, 95% CI ‐36.4 to ‐23.35), BMI (2 studies, 17 participants: MD ‐10.43 kg/m², 95% CI ‐13.58 to ‐7.29), and waist circumference (MD ‐30.00 cm, 95% CI ‐39.93 to ‐20.07) when compared to non‐surgical weight loss interventions after 12 months of follow‐up. Proteinuria and blood pressure were not reported.

All results across all comparators should be interpreted with caution due to the small number of studies, very low quality of evidence and heterogeneity across interventions and comparators.

Authors' conclusions

All types of weight loss interventions had uncertain effects on death and cardiovascular events among overweight and obese adults with CKD as no studies reported these outcome measures. Non‐surgical weight loss interventions (predominately lifestyle) appear to be an effective treatment to reduce body weight, and LDL cholesterol. Surgical interventions probably reduce body weight, waist circumference, and fat mass. The current evidence is limited by the small number of included studies, as well as the significant heterogeneity and a high risk of bias in most studies.

Plain language summary

Weight loss interventions for people with chronic kidney disease who are overweight or obese

What is the issue?

People who are overweight or obese with chronic kidney disease (CKD) may experience a faster progression to kidney failure than those who are a healthy weight. Some people with more advanced kidney disease may require treatment such as dialysis or a kidney transplant. Being obese can make these treatments difficult and may increase a person's risk of health complications. There is limited research looking at whether weight loss interventions are safe and beneficial to help people with CKD lose weight, improve their kidney function, and live longer.

What did we do?

We conducted a review of the literature to examine the benefits of weight loss interventions for people with CKD who are overweight or obese.

What did we find?

We identified 17 studies involving 988 overweight or obese adults with CKD looking at whether weight loss interventions improved their health. Studies included adults with CKD stages 1 to 4 or kidney transplant recipients. None of the studies included participants who were undergoing dialysis or supportive care. Weight loss interventions included weight loss diets, physical activity programs, drugs to suppress appetite, and weight loss surgery. The main outcomes we were interested in were death, cardiovascular events, weight loss, body mass index (BMI), waist circumference, protein in the urine (proteinuria), and blood pressure (BP).

After combining the available studies, its uncertain whether weight loss interventions helped people live longer or prevented cardiovascular events such as heart complications or stroke as none of the included studies measured these outcomes. We found when compared to no weight loss interventions, weight loss interventions may lead to more weight loss. There were little or no differences seen in BMI, waist circumference, proteinuria, or BP. We found that weight loss surgery achieved more weight loss than non‐surgical interventions. However, many of the studies included in this review were limited by small participant numbers, high risk of bias and inconsistent reporting of outcome measures leading to the overall quality of the evidence to be very low. This means that we cannot be sure that future studies would find similar results.

Conclusions

The evidence is not very certain but suggests that compared with usual care or control those who participated in weight loss interventions may experience some health benefits including improvements in body weight. Whether these benefits help reduce cardiovascular outcomes and the risk of death remains uncertain and require further study.

Summary of findings

Summary of findings 1. Any weight loss intervention compared to usual care or control.

Any weight loss intervention versus usual care/control for weight loss in people with chronic kidney disease (CKD) who are overweight or obese
Patient or population: people with CKD who are overweight or obese Setting: various (hospital outpatient clinic, research organisation) Intervention: any weight loss intervention Comparison: usual care or control
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with usual care/control	Risk with weight loss intervention
Death (any cause)	This outcome was not reported by any of the included studies	‐	‐	‐	‐	‐
Cardiovascular events	This outcome was not reported by any of the included studies	‐	‐	‐	‐	‐
Weight loss Follow up: range 5 weeks to 12 months	Mean weight loss ranged across control groups from 0.3 to 0.7 kg; mean post intervention body weight ranged from 86 to 136 kg The mean weight loss in the intervention group was 3.69 kg lower than the control group (5.82 lower to 1.57 lower)		‐	180 (6)	⊕⊝⊝⊝ VERY LOW 1 2 3 4	Majority of studies from lifestyle interventions No studies involving surgical interventions
Body mass index (BMI) Follow up: range 3 to 12 months	The mean BMI across control groups ranged from 28 to 38 kg/m² The mean BMI in the intervention group was 2.18 kg/m² lower than the control group (4.90 lower to 0.54 higher)		‐	100 (4)	⊕⊝⊝⊝ VERY LOW 1 2 3 4	All of studies from lifestyle interventions No studies involving pharmacological or surgical interventions
Waist circumference Follow up: range 3 to 12 months	The mean waist circumference across control groups ranged from 96 to 103 cm The mean weight circumference in the intervention group was 0.68 cm lower than the control group (7.6 lower to 6.24 higher)		‐	53 (2)	⊕⊝⊝⊝ VERY LOW 1 2 3 4	All of studies from lifestyle interventions No studies involving pharmacological or surgical interventions
Proteinuria Follow up: range 3 to 12 months	The mean proteinuria across control groups ranged from 0.5 to 3.5 g/day The mean proteinuria in the intervention group was 0.29 g/day lower than the control group (0.76 lower to 0.18 higher)		‐	84 (4)	⊕⊝⊝⊝ VERY LOW 1 2 3 4	All of studies from lifestyle interventions No studies involving pharmacological or surgical interventions
Systolic blood pressure (SBP) Follow up: range 3 to 6 months Diastolic blood pressure (DBP) Follow up: range 3 to 6 months	The mean SBP across control groups ranged from 123 to 140 mmHg The mean SBP in the intervention group was ‐3.45 mmHg lower than the control group (‐9.99 lower to 3.09 higher) The mean DBP across control groups ranged from 75 to 89 mmHg The mean DBP in the intervention group was ‐2.02 mmHg lower than the control group (‐3.79 lower to 0.24 higher)		‐	139 (4)	⊕⊝⊝⊝ VERY LOW 1 2 3 4	All of studies from lifestyle interventions No studies involving pharmacological or surgical interventions
CI: confidence interval; MD: mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹ Evidence certainty downgraded one level for indirectness

² Evidence certainty downgraded one level for imprecision

³ Evidence certainty downgraded one level for uncertain or high risk of bias

⁴ Evidence certainty downgraded one level for moderate heterogeneity

Background

Description of the condition

Obesity and chronic kidney disease (CKD) are highly prevalent worldwide and result in substantial healthcare burdens. Overweight and obesity are defined as ''abnormal or excessive fat accumulation that presents a risk to health'' and are commonly defined by a measure of body mass index (BMI) (WHO 2017). A BMI of > 25 kg/m² is considered overweight and a BMI > 30 kg/m² is considered obese. Since 1980, worldwide obesity has almost doubled and approximately 39% of adults are now overweight and 13% are obese (WHO 2017). In 2015, an increased BMI accounted for around 4 million deaths and 120 million disability‐adjusted life years (DALYs) worldwide (Afshin 2017).

CKD is defined as “kidney damage for ≥ 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased glomerular filtration rate (GFR) or GFR < 60 mL/min/1.73 m² for ≥ 3 months, with or without kidney damage” (KDIGO 2013). CKD is categorised into five stages, with the fifth stage, end‐stage kidney disease (ESKD) requiring kidney replacement therapy (KRT) for survival (KDIGO 2013). An estimated 11% to 13% of adults worldwide have CKD with the prevalence steadily increasing (Hill 2016). All stages of CKD have an increased risk of cardiovascular disease (CVD), increased death and poorer quality of life (van der Velde 2011; Weiner 2004). Global death rates for CKD rose by 41% between the years 1990 to 2016 (GBD 2016) and CKD is now the 13th leading male and 11th leading female risk of DALYs (GBD 2017) and accounts for 25% of all BMI‐related DALYs (Afshin 2017).

Obesity is considered a strong predictor of new onset of CKD and progression to ESKD (Kovesdy 2017; Tsujimoto 2014). In the general population, compared to those of a healthy weight (BMI of 20to 25 kg/m²), obese adults with a BMI ≥ 35 kg/m² are at a 122% increased risk of developing of ESKD (Herrington 2017). Obesity increases the risk of developing diabetes and hypertension, which are the two leading causes of CKD. Furthermore, in obese individuals, a compensatory hyperfiltration occurs to meet the increased metabolic demands of the higher body weight (Darouich 2011). The ensuing increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long term. For those who reach ESKD, obesity adversely affects eligibility for kidney transplantation (Ladhani 2017), with morbidly obese patients 44% less likely to receive a donor kidney (Segev 2008).

A recent systematic review exploring the association between obesity and cardiovascular morbidity and death in CKD (Ladhani 2017), highlighted that obesity (defined by BMI) may be protective for death (any cause) in the predialysis and haemodialysis (HD) populations, but not in peritoneal dialysis (PD) or transplant recipients. This relationship however is unlikely to be linear, with the highest risk of death occurring at extreme BMI categories. The biological rationale for the obesity paradox across different CKD stages remains unclear. It is proposed that obesity may lead to improved stem cell mobilisation, better bone strength, improved haemodynamic tolerance, and preserved energy stores (Stenvinkel 2008). However the relationship remains complex and is likely confounded by a number of factors including muscle mass, life expectancy, co‐morbidities, nutritional status, and measurement of obesity (Ladhani 2017; Stenvinkel 2008). These conflicting data demonstrate gaps in our current understanding of the links between obesity, kidney disease and clinical outcomes. Accordingly, this places emphasis on evaluating the safety and efficacy of weight loss interventions in obese or overweight patients with CKD (of various stages).

Description of the intervention

This review focused on interventions designed to promote intentional weight loss to improve patient outcomes. Weight loss interventions are typically aimed towards reducing an individual’s energy intake and/or increasing daily energy expenditure in order to induce weight loss, and can be broadly classified into lifestyle, pharmacological and surgical interventions. Lifestyle interventions included those exploring diet, physical activity, exercise, or behavioural strategies used in isolation or in combination to reduce energy intake and/or increase energy expenditure. Pharmacological interventions included interventions using drugs, which reduce absorption or suppress appetite. Surgical interventions included restrictive surgery designed to limit food intake (i.e. gastric banding or sleeve gastrectomy) or cause malabsorption (i.e. intestinal bypass) or both (i.e. gastric bypass). This review included these interventions used alone or in combination.

How the intervention might work

Both surgical and non‐surgical weight loss interventions have been explored in CKD patients, and may play an important role in slowing the progression of CKD and its associated risk factors; diabetes, hypertension, dyslipidaemia, and CVD (Ash 2006). While both weight loss interventions result in reductions in BMI, the magnitude is greater in those receiving surgical intervention (Bolignano 2013; Navaneethan 2009). Non‐surgical interventions have proven to be a successful and cost effective therapy in the CKD population; demonstrating short‐term weight reduction and corresponding improvements in systolic blood pressure (SBP), lipid profile and proteinuria (Bolignano 2013; Navaneethan 2009). However in practice many people are unable to maintain lifestyle change and regain lost body weight. Consequently these interventions may fail to achieve sustained weight loss, reductions in cardiorenal and metabolic risks and induce sufficient weight loss for transplant consideration in many obese patients (Weiner 2004). Bariatric surgery is currently considered the most effective weight loss intervention to achieve long‐term weight loss in morbidly obese individuals (Colquitt 2014); and has been evaluated in obese individuals with CKD as an approach to achieve sustained weight loss and examine kidney function (Chang 2017). Evidence from observational studies have shown that weight loss achieved through bariatric surgery can reduce the effects of CKD by reducing glomerular hyperfiltration, proteinuria, albuminuria, blood pressure (BP), hyperglycaemia and may induce diabetes remission (Bolignano 2013; Chang 2017). This may have important clinical applications as early bariatric surgery may assist with reversal of diabetes, hypertension and glomerular hyperfiltration possibly preventing further kidney injury. This may delay the need for KRT, open up opportunities for kidney transplantation and decrease the significant health burden associated with obesity and CKD.

Why it is important to do this review

The incidences of obesity and CKD continue to escalate and are contributing to more global death, morbidity, disability, and healthcare cost than ever before (Hill 2016). Whether weight loss can reverse these impacts however remains unclear and few practice guidelines exist regarding appropriate strategies for weight management in people with CKD (Lambert 2017). Reducing and managing obesity may reverse or slow CKD progression and enable transplantation as a treatment option for more individuals (Chang 2017; Lassalle 2017). However, weight loss interventions in people with CKD are not without risk. Lifestyle interventions such as very low energy diets may cause electrolyte disturbances, fluid overload, constipation, uraemia, and blood glucose disturbances in those with diabetes (Lambert 2017). Weight loss medication such as lipase inhibitors may cause steatorrhoea, abdominal pain, flatulence, and increase the risk of oxalate nephropathy and kidney stones (Navaneethan 2009). Surgical interventions may be associated with higher rates of complications, such as band erosion, gastric leak and acute kidney injury (AKI) when compared with the non‐CKD population and surgeries featuring malabsorption appear to increase the risk of nephrolithiasis and oxalate nephropathy (Chang 2017; Weiner 2004). Furthermore highly restrictive diets post bariatric surgery can lead to dietary intakes well below recommended daily nutrient targets increasing risk of long‐term nutrient deficiencies (Colquitt 2014). This systematic review aimed to provide a current and comprehensive review of weight reduction interventions in CKD by including both overweight and obese adults at all stages of CKD (including pre dialysis, dialysis, supportive care, or kidney transplantation). This will provide a better understanding of the balance of benefits and harms of weight loss in CKD which will help better inform clinical decision‐making by clinicians, patients, and their caregivers.

Objectives

This review aimed to evaluate the safety and efficacy of intentional weight loss interventions in overweight and obese adults with CKD; including those with ESKD being treated with dialysis, kidney transplantation, or supportive care.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) and quasi RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the efficacy of intentional weight loss interventions in adults with CKD.

Types of participants

Inclusion criteria

Adults who were overweight (as defined by BMI 25 kg/m² to 29.9 kg/m²) or obese (as defined by BMI ≥ 30 kg/m²) (WHO 2017) with pre‐existing CKD defined by the Kidney Disease: Improving Global Outcomes (KDIGO 2013) "kidney damage for ≥ 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, or GFR < 60 mL/min/1.73m² for ≥ 3 months, with or without kidney damage". The review included individuals with CKD or ESKD treated with dialysis (both HD and PD), kidney transplantation, or supportive care.

Subgroup data from studies who had participants meeting our inclusion criteria were included in the review if data were available for those who met the inclusion criteria. In studies where subgroup data for those who met the inclusion was not available, if > 75% of participants met the inclusion criteria then the study with the whole group analysis were included in the review.

Exclusion criteria

The review excluded studies involving pregnant women, children (younger than 18 years) and people with an AKI.

Types of interventions

We investigated studies reporting on intentional weight loss interventions of at least four weeks in duration, designed to promote weight loss as one of their primary stated goals, in any health care setting.

These studies included:

• Lifestyle interventions, including dietary interventions (i.e. energy restricted diet, very low energy dense diet), physical activity interventions (i.e. aerobic exercise, resistance exercise, group exercise programs), behavioural change interventions (strategies to assist with lifestyle modification i.e. self‐monitoring of eating habits, stress management), and combination lifestyle interventions (using any combination of diet, exercise and/or behavioural interventions)

• Pharmacological interventions, including appetite suppressants, drugs that cause fat malabsorption of any dose and route, pharmacological plus lifestyle interventions.

• Surgical interventions, including sleeve gastrectomy, gastric banding, or bypass procedure

We planned to compare any of these interventions with any other intervention, placebo, or usual care. The comparisons separated by intervention type were as follows:

1. Any weight loss intervention versus usual care or control (main comparison)

2. Any weight loss intervention versus dietary intervention and

3. Surgical intervention versus non‐surgical intervention

Types of outcome measures

Primary outcomes

• Death (any cause)

• Cardiovascular events

• Anthropometric measures (weight loss, body weight, BMI, waist circumference, waist‐to‐hip ratio, and body composition)

Secondary outcomes

1. Clinical parameters

• Kidney function measures: measured GFR, creatinine clearance (CrCl), serum creatinine (SCr), proteinuria, albuminuria, glomerular hyperfiltration (as defined and measured by study investigators). These parameters were assessed in participants with CKD stages 1 to 4 and those who have had a kidney transplant. These parameters were not assessed in participants undergoing dialysis.

• BP: SBP and diastolic (DBP), anti‐hypertensive medication changes

• Blood glucose: glycosylated haemoglobin (HbA1c), fasting blood glucose, hypoglycaemic medication changes

• Lipid profile: total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, lipid lowering medication changes

• Successful kidney transplantation

• Inflammation (C‐reactive protein).

2. Patient‐centred outcomes using validated tools or self‐reported data

• Adherence to treatment

• Health‐related quality of life (HRQoL)

• Nutritional status

• Dietary intake

• Physical activity behaviours.

3. Cost effectiveness and economic analysis

• Cost per DALYs or quality‐adjusted life year (QALY)

• Cost associated with weight loss intervention.

4. Adverse events and potential harms

• Hospitalisation

• Adverse patient outcomes associated with each weight loss intervention

• Biochemical adverse effects such as hyperkalaemia or hyperphosphataemia.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Kidney and Transplant Specialised Register up to 14 December 2020 through contact with the Information Specialist using search terms relevant to this review. The Cochrane Kidney and Transplant Specialised Register contains studies identified from several sources.

1. Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)

2. Weekly searches of MEDLINE OVID SP

3. Searches of kidney and transplant journals, and the proceedings and abstracts from major kidney and transplant conferences

4. Searching of the current year of EMBASE OVID SP

5. Weekly current awareness alerts for selected kidney and transplant journals

6. Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Studies contained in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of search strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available on the Cochrane Kidney and Transplant website.

See Appendix 1 for search terms used in strategies for this review.

Searching other resources

1. Reference lists of review articles, relevant studies, and clinical practice guidelines.

2. Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.

Data collection and analysis

Selection of studies

We used the search strategy described to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts were screened independently by two authors. Studies that were not relevant were discarded. However studies and reviews thought to include relevant data or information on studies were retained initially. Two authors independently assessed retrieved abstracts, and when necessary the full text of these studies to determine which studies satisfied the inclusion criteria. Any differences were resolved by discussion and, when necessary, by consultation with a third author.

Data extraction and management

For the studies that fulfilled the inclusion criteria, data extraction was carried out by two independent authors using standard data extraction forms. Studies reported in non‐English language were translated before assessment. Where more than one publication from the same study was found, reports were grouped together and the publication with the most complete data was used in the analyses. Where relevant outcomes were only published in earlier versions, these data were used. Any discrepancy between published versions were highlighted and any disagreements that were not resolved through discussion between the two authors were resolved in consultation with a third author.

Assessment of risk of bias in included studies

The following items were independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2).

• Was there adequate sequence generation (selection bias)?

• Was allocation adequately concealed (selection bias)?

• Was knowledge of the allocated interventions adequately prevented during the study?

  • Participants and personnel (performance bias)

  • Outcome assessors (detection bias)

• Were incomplete outcome data adequately addressed (attrition bias)?

• Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?

• Was the study apparently free of other problems that could put it at a risk of bias?

Measures of treatment effect

For dichotomous outcomes (e.g. death, CVD), results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment (anthropometric and biochemical markers), the mean difference (MD) was used, or the standardised mean difference (SMD) was used if different scales were used.

Unit of analysis issues

Cluster‐randomised studies

There were no cluster‐randomised studies included in this meta‐analysis.

Cross‐over studies

Cross‐over studies were analysed using only the data from the first period.

Studies with more than two treatment arms

Studies with multiple intervention groups were included. When considering these studies we tried to combine all relevant experimental intervention groups of the study into a single group and combined all relevant control intervention groups into a single group to enable single pair wise comparison.

Dealing with missing data

Any further information required from the original authors was requested by written correspondence (emailing corresponding author) and any relevant information obtained in this manner was included in the review. Evaluation of important numerical data, such as number of patients screened, randomised patients as well as intention‐to‐treat, as‐treated and per‐protocol populations, was performed. Attrition rates, for example drop‐outs, losses to follow‐up and withdrawals were investigated. Issues of missing data and imputation methods (for example, last‐observation‐carried‐forward) were critically appraised (Higgins 2011).

Assessment of heterogeneity

We first assessed the heterogeneity by visual inspection of the forest plot. Heterogeneity was then analysed using the I² statistic, which describes the percentage of total variation across studies that is due to heterogeneity rather than sampling error (Higgins 2003). A guide to the interpretation of I² values was as follows.

• 0% to 40%: might not be important

• 30% to 60%: may represent moderate heterogeneity

• 50% to 90%: may represent substantial heterogeneity

• 75% to 100%: considerable heterogeneity

The importance of the observed value of I² depends on the magnitude and direction of treatment effects and the strength of evidence for heterogeneity (e.g. P‐value from the Chi² test, or a confidence interval for I²) (Higgins 2011).

Assessment of reporting biases

Due to the small number of studies we were unable to assess for the existence of small study bias using funnel plots.

Data synthesis

We classified our studies by type of intervention lifestyle: including dietary, physical activity, behaviour change, pharmacological and surgical interventions. Data were summarised using the random‐effects model although the fixed‐effects model was also analysed to ensure robustness of the model chosen and susceptibility to outliers. When evidence of sizeable clinical, methodological, and statistical heterogeneity across included studies was evident across studies we were not able to pool results to from a meta‐analysis and instead a reported a narrative approach to this data synthesis.

Subgroup analysis and investigation of heterogeneity

To explore for possible sources of heterogeneity in our protocol we stated we would conduct the following subgroup analyses if adequate data were available.

• BMI (overweight versus obese)

• Stage of CKD and modality (HD, PD, transplantation, supportive care)

• Duration of intervention (≤ 3 months versus > 3 months)

• Chief causes of CKD, (diabetes, hypertension, glomerulonephritis, polycystic kidney disease, reflux kidney disease)

• Presence or absence of proteinuria

Sensitivity analysis

Where sufficient studies were available, we investigated the following:

• Repeating the analysis excluding unpublished studies;

• Repeating the analysis taking account of risk of bias, as specified;

• Repeating the analysis excluding any very long or large studies to establish how much they dominate the results; and

• Repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), country.

Summary of findings and assessment of the certainty of the evidence

We presented the main results of the review in 'Summary of findings' tables. These tables present key information concerning the quality of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schunemann 2011a). The 'Summary of findings' tables also include an overall grading of the evidence related to each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach (GRADE 2008; GRADE 2011). The GRADE approach defines the quality of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The quality of a body of evidence involves consideration of within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schunemann 2011b).

The key outcomes presented in the Summary of findings Table 1 include:

1. Death (any cause)

2. Cardiovascular events

3. Weight loss/post intervention body weight

4. BMI

5. Waist circumference

6. Proteinuria

7. BP: SBP and DBP.

Results

Description of studies

For a detailed description of studies, see Characteristics of included studies; Characteristics of excluded studies and Characteristics of ongoing studies sections.

Results of the search

The electronic search of the Cochrane Kidney and Transplant Specialised Register (up to 14 December 2020) identified 154 records. An additional 39 records were found when we searched the reference lists of included studies and relevant reviews, resulting in a total of 193 unique records.

We screened the titles and abstracts of these 193 records and a further 84 records were excluded (not randomised, wrong population and/or interventions). We obtained and reviewed the remaining 109 full‐text records (33 studies). A further 55 records were excluded (not intentional weight intervention studies, ≤ 4 weeks duration). Two ongoing studies were identified (HHK 2018; Spaggiari 2020); these studies will be assessed in a future update of this review. Thirty‐three records from 17 studies met the inclusion criteria (see Figure 1).

1.

Study flow diagram.

Included studies

The Characteristics of included studies table provides details of the included studies. The following gives a brief overview.

Included studies were published between 1975 and 2019. Data were obtained from both published literature, supplementary unpublished data, and trial registers. Additional data were requested for 11 studies via correspondence with study authors (see Appendix 3). One study was translated from Czech to English (Teplan 2006).

Study design

This review included 17 studies (51 reports; 988 randomised participants). Sixteen studies had a parallel design and one study (Tomlinson 1975) had a cross‐over design. The majority (11) were single centre studies (Baria 2014; DIRECT 2013; Jesudason 2013; Kittiskulnam 2014; LANDMARK 3 2013; Leehey 2009; Leehey 2016; Morales 2003a; Orazio 2011; Praga 1995; Tomlinson 1975) and were carried out in hospital outpatient clinics (Baria 2014; Ikizler 2018; Kittiskulnam 2014; LANDMARK 3 2013; Leehey 2009; Leehey 2016; MacLaughlin 2014; Morales 2003a; Orazio 2011; Praga 1995; Tomlinson 1975).

Location of studies

Five of the 17 included studies were conducted in the USA (Ikizler 2018; Leehey 2009; Leehey 2016; Tzvetanov 2015; Woolf 2017), three were in Australia (Jesudason 2013; LANDMARK 3 2013; Orazio 2011), two each in Spain (Morales 2003a; Praga 1995), the UK (MacLaughlin 2014; Tomlinson 1975) and Czech Republic (Teplan 2002; Teplan 2006), and one study each in Thailand (Kittiskulnam 2014), Israel (DIRECT 2013) and Brazil (Baria 2014).

Participants

The included studies involved a total of 988 overweight or obese participants with CKD. The number of participants in included studies ranged from 6 to 258. The mean age of participants was 42.5 ± 4.5 to 65.9 ± 9.7 years. Thirteen studies (620 participants) investigated the effects of weight loss in people with CKD stages 1 to 4 and four studies (368 participants) were conducted with transplant recipients (Orazio 2011; Teplan 2002; Tomlinson 1975; Tzvetanov 2015). None of the included studies involved participants undergoing dialysis (HD or PD) nor supportive care.

Comparisons

We identified three comparisons for analysis, separated by intervention type.

1) Any weight loss intervention versus usual care or control (main comparison)

Lifestyle versus usual care

• Dietary versus usual care or control

  • Morales 2003a evaluated a daily energy restriction of 2100 kJ versus usual dietary intake

  • Kittiskulnam 2014 compared a daily energy restriction of 2100 kJ with a daily protein target of 0.6 to 0.8 g/kg/day versus no energy restriction and a daily protein target of 0.6 to 0.8g/kg/day

  • Praga 1995 evaluated a daily energy intake of 4200 to 5900 kJ/day versus usual diet habits plus captopril treatment.

• Physical activity versus usual care or control

  • Baria 2014 evaluated the effects of in‐centre and home‐based aerobic exercise performed 3 times/week for 12 weeks versus control

  • Leehey 2009 compared the effects of 3 times/week aerobic exercise training for 6 weeks in centre followed by 18 weeks of supervised home exercise versus usual care.

• Behavioural versus usual care or control

  • Woolf 2017 compared the differences in weight between an intensive Social Cognitive Theory–based lifestyle intervention to a standard behaviour treatment over 6 months.

• Mixed lifestyle versus usual care or control

  • The effects of lifestyle intervention consisting of dietary modifications and increasing physical activity on metabolic outcomes compared to usual care was examined in CKD recipients in two studies (Ikizler 2018; LANDMARK 3 2013) and in transplant recipients in one study (Orazio 2011).

Pharmacological versus usual care or control

• Appetite suppressant versus dietary

  • Tomlinson 1975 (trial 2) evaluated the effects of fenfluramine compared to placebo over 6 weeks among transplant recipients.

Mixed intervention versus usual care or control

• Lifestyle (dietary) plus pharmacological (appetite suppressant) versus usual care or control

  • Teplan 2002 assessed the effects of a hypo‐energetic and hypolipidaemic diet supplemented with orlistat compared to usual care over 3 years.

2) Any weight loss intervention versus dietary intervention

Lifestyle (dietary) versus lifestyle (dietary)

• DIRECT 2013 explored the effects of 3 different diets; a low fat energy restricted diet (6300 kJ for women and 7500 kJ for men with a goal of 30% energy coming from fat); a Mediterranean energy restricted diet (6300 kJ for women and 7500 kJ for men, goal no more than 35% of energy from fat, main sources of fat were 30 to 45 g of olive oil and a handful of nuts per day) and a low carbohydrate non‐energy restricted diet (modified Atkins diet ‐ goal for 20 g of carbohydrates per day for the 2‐month induction phase gradual increase to a maximum of 120 g/day ‐ the intake of total energy, protein, and fat were not limited).

• Teplan 2006 investigated the effects of a low protein (0.6 g/kg/day) and energy restricted diet (120 to 125 kJ/kg/day for the first 6 months then 125 to 130 kJ/kg/day thereafter for 3 years) supplemented twice with either keto acid supplementation or placebo.

• Jesudason 2013 evaluated the effects of a moderate versus standard protein weight loss diet 6000 kJ/day for women, or 7000 kJ/day for men with either a protein intake goal of 90 to 120 g/day (moderate protein) or 55 to 70 g/day (standard protein).

Lifestyle (dietary and exercise) versus lifestyle (dietary)

• Leehey 2016 examined the effects of an exercise and diet intervention (12 weeks of 3 times/week exercise training followed by 40 weeks of supervised home exercise plus daily 800 to 1000 kJ energy restriction) versus usual medical care.

Lifestyle (dietary) versus lifestyle (dietary)

• DIRECT 2013, Jesudason 2013 and Teplan 2006 examined the effects of various energy restricted diets on weight loss and kidney function.

Pharmacological (appetite suppressant) versus dietary

• Tomlinson 1975 (trial 1) evaluated the effects of fenfluramine compared to placebo over 6 weeks.

3) Surgical intervention versus non‐surgical intervention

Surgical (sleeve gastrectomy) versus lifestyle (standard weight loss program)

• Tzvetanov 2015 explored the effectiveness of combined robotic kidney transplantation and sleeve gastrectomy versus robotic kidney transplantation and standard weight loss program.

Surgical (sleeve gastrectomy) versus pharmacological (lipase inhibitor) and lifestyle (dietary)

• MacLaughlin 2014 explored the effect of sleeve gastrectomy compared to best medical care (individualised dietary and physical activity prescription plus orlistat).

A summary of included studies and the types of weight loss interventions and the main comparators used can be found in Appendix 4. Most (13 studies) explored the effects of lifestyle weight loss. Of these, eight compared lifestyle interventions against usual care or control (Baria 2014; Kittiskulnam 2014; LANDMARK 3 2013; Leehey 2009; Morales 2003a; Orazio 2011; Praga 1995; Woolf 2017), four compared lifestyle interventions to other lifestyle interventions (DIRECT 2013; Jesudason 2013; Leehey 2016; Teplan 2006) and one study (Ikizler 2018) compared the effects of three different lifestyle interventions to usual activity and diet. Two studies explored the efficacy of pharmacological interventions (Teplan 2002; Tomlinson 1975) and two studies compared mixed interventions not involving bariatric surgery to bariatric surgery (MacLaughlin 2014; Tzvetanov 2015).

Excluded studies

During the full text screening a total of 55 records (14 studies) were excluded. The main reasons for exclusion were not a weight loss intervention or study duration < 4 weeks. See Characteristics of excluded studies table for reasons for excluding each study.

Risk of bias in included studies

For details on risk of bias of included studies, see Characteristics of included studies. Methodological quality was quite varied, with many studies providing insufficient information to accurately judge the risk of bias. A summary of authors' judgements of the risk of bias for all included studies are shown in Figure 2; and risk of bias in each individual study is shown in Figure 3.

2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Random sequence generation

Random sequence generation was judged as low risk of bias in nine studies (DIRECT 2013; Ikizler 2018; Jesudason 2013; Kittiskulnam 2014; LANDMARK 3 2013; Leehey 2009; Leehey 2016; MacLaughlin 2014; Teplan 2006) and unclear in the remaining eight studies.

Allocation concealment

Four studies (Jesudason 2013; Leehey 2016; MacLaughlin 2014; Tomlinson 1975) described allocation concealment methods and all were assessed as low risk of bias. In the remaining 13 studies the risk of bias was unclear as the method of concealment was not adequately described to permit judgement.

Blinding

Performance bias: participants

We judged two studies (Teplan 2006; Tomlinson 1975) to have a low risk of performance bias as participants were blinded to treatment allocation. We judged 11 studies as being at high risk of performance bias (Baria 2014; DIRECT 2013; Ikizler 2018; Jesudason 2013; Kittiskulnam 2014; LANDMARK 3 2013; Leehey 2009; Leehey 2016; MacLaughlin 2014; Morales 2003a; Orazio 2011) and four studies as having unclear risk of performance bias (Praga 1995; Teplan 2002; Tzvetanov 2015; Woolf 2017).

Performance bias: personnel

The risk of performance bias was assessed as being low in three studies (DIRECT 2013; Teplan 2006; Tomlinson 1975) high in five studies (Ikizler 2018; Kittiskulnam 2014; LANDMARK 3 2013; Leehey 2016; Morales 2003a) and unclear in nine studies (Baria 2014; Jesudason 2013; Leehey 2009; MacLaughlin 2014; Orazio 2011; Praga 1995; Teplan 2002; Tzvetanov 2015; Woolf 2017).

Detection bias

We assessed the risk of detection bias for objective outcomes as low for all studies regardless of whether or not outcome assessors were blinded.

In the seven studies that included subjective outcomes measures we judged detection bias to be low in two studies (DIRECT 2013; Leehey 2016), high in one study (Kittiskulnam 2014) as they did not undertake blinding of outcome assessors, and unclear in four studies (Baria 2014; Jesudason 2013; LANDMARK 3 2013; MacLaughlin 2014) because blinding was not adequately reported.

Incomplete outcome data

Only five studies (Baria 2014; DIRECT 2013; Ikizler 2018; Kittiskulnam 2014; LANDMARK 3 2013) were considered to be at low risk of attrition bias. Three studies (Jesudason 2013; MacLaughlin 2014; Tomlinson 1975) were assessed to be at high risk of bias as more than 20% of participants were lost to follow‐up. Attrition bias in the remaining nine studies was judged unclear due to insufficient information.

Selective reporting

We judged studies to be at high risk of reporting bias if planned outcomes were not adequately reported. Four studies (DIRECT 2013; LANDMARK 3 2013; Leehey 2009; Teplan 2002) were judged to be at low risk of selective reporting bias. Three studies (Jesudason 2013; MacLaughlin 2014; Praga 1995) were judged to be at high risk of selective reporting bias, and 10 studies were judged unclear risk due to insufficient information available to permit judgement.

Other potential sources of bias

Two studies were assessed as high risk of other bias: MacLaughlin 2014 used blocked randomisation in an unblinded RCT and the study had a very low recruitment uptake of 10%, and DIRECT 2013 used post hoc reporting of sub‐groups with CKD stages 3 to 4. Five studies (Baria 2014; Ikizler 2018; Morales 2003a; Orazio 2011; Tomlinson 1975) appeared to be free of other sources of bias and were judged low risk. The remaining 10 studies were assessed to have unclear risk of bias due to insufficient information to permit judgement.

Effects of interventions

See: Table 1

See Table 1 for the main comparison weight loss interventions (lifestyle, pharmacological, bariatric surgery) compared to usual care or placebo in CKD populations.

The studies were analysed using both random effects and fixed effects models and found no difference between the two models. The results below therefore refer to those obtained using a random‐effects model.

Primary outcomes

Death (any cause) and cardiovascular events

None of the included studies evaluated the effects of weight loss on death or cardiovascular events.

Weight loss

Weight loss interventions compared to usual care or control may lead to weight loss and reduced post intervention body weight (Analysis 1.1 (6 studies, 180 participants): MD ‐3.69 kg, 95% CI ‐5.82 to ‐1.57; I² = 59%). The certainty of the evidence was very low due to high or uncertain risk of bias, moderate heterogeneity, imprecision, and indirectness. Three additional studies (Ikizler 2018; Tomlinson 1975; Woolf 2017) had data which could not be statistically pooled, however were consistent with the meta‐analysis, with all three reporting significant improvements in body weight in the weight loss intervention groups compared to their respective control.

1.1. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 1: Mean weight loss [kg] or post intervention body weight

There was little or no difference between any weight loss intervention compared to dietary interventions for weight loss (Analysis 2.1 (3 studies, 155 participants): MD 0.76 kg, 95% CI ‐2.125 to 3.66; I² = 0%). Ikizler 2018 could not be pooled however reported similar findings to the meta‐analysis. DIRECT 2013, which had three different dietary arms, remained robust to the primary finding when each intervention comparison was rotated through Analysis 2.1.

2.1. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 1: Mean weight loss [kg] or post intervention body weight

MacLaughlin 2014 reported surgical intervention participants (sleeve gastrectomy) lost 29.50 kg (95% CI 23.35 to 35.65 kg) more weight compared to control participants who received a combined diet and pharmacological treatment.

Stage of chronic kidney disease

There was no little or no difference in total weight loss following any weight loss intervention compared to usual care or control in CKD stages 1 to 4 (Analysis 4.1.1) or in transplant recipients (Analysis 4.1.2).

4.1. Analysis.

Comparison 4: Weight loss intervention versus usual care or control: stage of CKD, Outcome 1: Mean weight loss [kg or %]

Intervention duration

There was little or no difference in total weight loss for any weight loss intervention given for 3 months or less (Analysis 5.1.1) or interventions given for more than 3 months (Analysis 5.1.2). The test for subgroup differences showed no difference between the two time frames (test for subgroup differences: Chi² = 0.02, df = 1 (P = 0.88), I² = 0%).

5.1. Analysis.

Comparison 5: Weight loss intervention versus usual care or control: duration of intervention, Outcome 1: Mean weight loss: post intervention body weight

Body mass index

Weight loss interventions had uncertain effects on BMI (Analysis 1.2 (4 studies, 100 participants): MD ‐2.18 kg/m², 95% CI ‐4.90 to 0.54; I²= 60%). The certainty of the evidence was very low due to high or uncertain risk of bias, moderate heterogeneity, imprecision, and indirectness. Five studies were unable to be meta‐analysed; all found any weight loss interventions led to significantly lower BMI when compared to usual care or control (Ikizler 2018; LANDMARK 3 2013; Orazio 2011; Teplan 2002; Tzvetanov 2015).

1.2. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 2: Body mass index

In studies involving any weight loss intervention compared to dietary intervention there was little or no difference to post‐intervention BMI (Analysis 2.2 (3 studies, 262 participants): MD ‐1.27 kg/m², 95% CI ‐4.43 to 1.89; I² = 87%).

2.2. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 2: Body mass index

In studies involving surgical interventions BMI was probably reduced in sleeve gastrectomy when compared to non‐surgical interventions (Analysis 3.2 (2 studies, 17 participants): MD ‐10.43 kg/m², 95% CI ‐13.58 to ‐7.29: I² = 42%).

3.2. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 2: Body mass index

Intervention duration

Weight loss interventions given for more than 3 months probably reduced BMI (Analysis 5.2.3 (3 studies, 73 participants): MD ‐3.36 kg/m², 95% CI ‐5.68 to ‐1.04; I² = 9%), whereas interventions given for 3 months or less possibly made little of no difference to BMI (Analysis 5.2.1).

5.2. Analysis.

Comparison 5: Weight loss intervention versus usual care or control: duration of intervention, Outcome 2: Body mass index

Waist circumference

Two studies using dietary intervention (Kittiskulnam 2014) and exercise (Baria 2014) showed little or no difference to waist circumference when compared to usual care (Analysis 1.3 (2 studies, 53 participants) MD ‐0.68 cm, 95% CI ‐7.6 to 6.24; I² = 40%). The certainty of evidence was very low due to high or uncertain risk of bias, moderate heterogeneity, imprecision, and indirectness. Two studies (LANDMARK 3 2013; Orazio 2011) could not be pooled into the meta‐analysis. Orazio 2011 also found no difference between the two groups, while LANDMARK 3 2013 reported significant reductions in waist circumference following a combined diet and exercise intervention compared to usual care.

1.3. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 3: Waist circumference

DIRECT 2013 compared weight loss interventions to dietary interventions and reported no effect on waist circumference across three different dietary interventions (low‐fat, low‐carbohydrate, and Mediterranean diet) in CKD participants.

MacLaughlin 2014 compared surgical to non‐surgical interventions and reported waist circumference was reduced following sleeve gastrectomy surgery compared to a combined pharmacological and diet intervention in CKD participants (Analysis 3.1 (1 study, 11 participants): MD ‐30.00 cm, 95% CI ‐39.93 to ‐20.07).

3.1. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 1: Mean weight loss (change score)

Waist‐to‐hip ratio

Two studies comparing weight loss intervention to usual care or control had uncertain effects on waist‐to‐hip ratio. Orazio 2011 reported no difference in waist‐to‐hip ratio between the two groups following a 6‐month dietary and exercise intervention (MD ‐1.05, 95% CI ‐5.92 to 3.82). Ikizler 2018 reported a reduction in waist‐to‐hip ratio in the dietary energy restricted group compared to the usual diet group (P = 0.03), but not in the exercise‐only intervention (P = 0.72).

In studies comparing any weight loss intervention to diet intervention, Teplan 2006 reported waist‐to‐hip ratio reduced by ‐0.05 units (95% CI ‐0.07 to ‐0.03) in participants following an energy restricted diet with concurrent keto‐amino acid supplementation compared to those following a low protein and energy restricted diet with placebo supplementation.

Body composition measures (fat mass, lean body mass and muscle mass)

Four studies comparing weight loss intervention to usual care or control, had uncertain effects on fat mass and lean body mass.

• Kittiskulnam 2014 reported a reduced body fat (24.8% compared to 26.2%, measured by bioelectrical impedance analysis (BIA)) and no change in muscle mass, in a diet‐only intervention compared to usual care. In contrast, Leehey 2009 found no effect on body fat or lean body mass (measured by air displacement plethysmography) following 24 weeks of aerobic exercise.

• Baria 2014 had mixed results, finding an exercise‐only intervention to have no effect on total body fat (measured by dual‐energy X‐ray absorptiometry (DEXA) scan) following either in‐centre exercise or home‐based exercise. However, exercise intervention groups had reductions in visceral fat when compared to control. After 12 weeks of aerobic exercise the in‐centre exercise group saw improvements in total lean body mass (kg) due to an increase in leg lean mass however these benefits were not achieved in the home exercise group nor control group.

• Ikizler 2018 reported a reduction in body fat (measured by DEXA) with a combined diet and exercise intervention compared to usual care (MD ‐0.5%, 95% CI ‐1.9 to 0.8) as well as in the diet‐alone intervention reduced body fat compared to usual care (MD ‐1.6%, 95% CI ‐2.9 to ‐0.3). However the exercise‐alone intervention compared to usual care did not show a reduction in body fat.

Comparing any weight loss intervention to dietary interventions had uncertain effects on body composition.

• Jesudason 2013 compared energy restricted diets with different levels of protein and reported weight loss resulted in a fat mass loss (measured by DEXA scan in 42 participants) of 6.2 ± 7.7 kg in the moderate protein group and 4.9 ± 5.1 kg in the standard protein group. Similar lean fat mass changes were also reported amongst groups: 1.7 ± 2.7 kg in the moderate protein group and 1.8 ± 2.9 kg in the standard protein group.

• Leehey 2016 reported no change in fat mass (kg), percentage body fat, or lean weight (kg) (measured by air displacement plethysmography) in either the exercise and diet group or diet alone group.

• Teplan 2006 reported a greater reduction in visceral fat (measured by magnetic resonance spectroscopy) in those following an energy restricted lower protein diet supplemented with keto‐amino acid supplementation then those following an energy restricted lower protein diet with placebo supplementation.

MacLaughlin 2014 reported surgical intervention participants lost 24.1 kg (95% CI 32.5 to 15.7) more fat mass (measured by BIA) compared to best medical care control participants who received combined lifestyle and pharmacological treatment.

Secondary outcomes

Creatinine clearance

Weight loss interventions had uncertain effects on CrCl when compared to usual care or control (Analysis 1.5 (3 studies, 58 participants): SMD 0.29, 95% CI ‐0.34 to 0.91: I² = 20%). Teplan 2002, reported a significant reduction in CrCl in transplant recipients following a combined diet and pharmacological intervention (from 1.2 mL/s at baseline to 0.9 mL/s at 3‐year follow‐up), however no comparison data for the usual care arm was reported.

1.5. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 5: Creatinine clearance [points]

Teplan 2006 reported a significant reduction post intervention in CrCl in the weight loss intervention (low protein and energy restricted diet with concurrent keto‐amino acid supplementation) of 33.5 mL/min/1.73 m² compared to 25.8 mL/min/1.73 m² in the low protein and energy restricted diet group with placebo supplementation.

Serum creatinine

Weight loss interventions compared to usual care or control had uncertain effects on SCr (Analysis 1.6 (4 studies, 84 CKD participants): MD ‐0.15 mg/dL, 95% CI ‐0.52 to 0.22); I² = 23%). The quality of evidence was considered to be low due to high or uncertain risk of bias, and imprecision (small sample size).

1.6. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 6: Serum creatinine

MacLaughlin 2014 reported no statistically significant change in SCr in CKD participants following a surgical (sleeve gastrectomy) intervention compared to a combined pharmacological and diet therapy.

Proteinuria

Weight loss interventions compared to usual care or control had uncertain effects on proteinuria (Analysis 1.7 (4 studies, 84 participants): MD ‐0.29 g/day, 95% CI ‐0.76 to 0.18: I² = 33%). The certainty of evidence was very low due to high or uncertain risk of bias, imprecision, and indirectness. Teplan 2002 reported a reduction in proteinuria in transplant recipients following a combined diet and pharmacological intervention, however no data for the control arm was reported.

1.7. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 7: Proteinuria

Leehey 2016 reported a combined diet and exercise intervention in CKD participants reduced proteinuria compared to a diet‐only intervention (405 mg/g compared to 618 mg/g), respectively.

Albuminuria

Three studies conducted in CKD participants reported on albuminuria and all reported no effect following an exercise intervention compared to usual care (Leehey 2009), standard protein energy restricted diet compared to a moderate protein energy restricted diet (Jesudason 2013), and diet and exercise intervention versus diet alone (Leehey 2016).

Measured GFR

Weight loss interventions versus dietary intervention and had uncertain effects on measured GFR. Teplan 2006 reported a change in measured GFR with an energy restricted diet supplemented with keto‐amino acids compared to an energy restricted low protein diet, and Jesudason 2013 reported a change in measured GFR with a moderate protein energy restricted diet compared to a standard protein energy restricted diet (Analysis 2.7 (2 studies, 176 CKD participants): SMD 0.63, 95% CI 0.25 to 1.02: I² = 29%).

2.7. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 7: Measured GFR

Glomerular hyperfiltration

Jesudason 2013 reported weight loss in both the energy restricted moderate protein and standard protein diets resulted in a decline in eGFR of 15 mL/min in participants with hyperfiltration (defined by a GFR > 120 mL/min).

Blood pressure

Weight loss interventions had an uncertain effect on SBP (Analysis 1.8 (4 studies, 139 CKD participants): MD ‐5.90 mmHg, 95% CI –13.75 to 1.96: I² = 64%) and DBP (Analysis 1.9 (4 studies, 139 CKD participants): MD ‐5.49 mmHg, 95% CI –11.13 to 0.14: I² = 63%) when compared to usual care or control. The certainty of evidence was very low due to high or uncertain risk of bias, imprecision, and indirectness. Ikizler 2018 reported median data which could not be pooled, however commensurate with our meta‐analysis, they found no significant reduction in SBP or DBP following a combined diet and exercise intervention, or in diet‐ or exercise‐alone interventions, compared to usual care.

1.8. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 8: Systolic blood pressure

1.9. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 9: Diastolic blood pressure

Any weight loss interventions made little or no difference to SBP compared to dietary interventions (Analysis 2.8 (3 studies, 262 CKD participants): MD ‐2.33 mmHg, 95% CI ‐8.32 to 3.67: I² = 71%), which remained robust with substitution as each of the three dietary arms were rotated through the meta‐analysis from DIRECT 2013. Jesudason 2013 similarly reported no change in SBP following a standard protein energy restricted diet compared to a moderate protein energy restricted diet, however, did not report the outcome data to allow for data pooling.

2.8. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 8: Systolic blood pressure

In contrast, DBP was probably reduced with any weight loss intervention when compared to diet‐alone comparators (Analysis 2.9 (3 studies, 246 CKD participants): MD ‐1.87 mmHg, 95% CI ‐3.59 to ‐0.14: I² = 0%).

2.9. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 9: Diastolic blood pressure

Anti‐hypertensive medication changes

Morales 2003a reported that the numbers, classes, and doses of antihypertensive drugs administered to both the dietary intervention group and control group were similar.

Glycosylated haemoglobin

Weight loss interventions had uncertain effect on HbA1c versus usual care or control (Analysis 1.10 (2 studies, 83 CKD participants): MD ‐0.48%, 95% CI ‐1.15 to 0.18: I2 = 0%).

1.10. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 10: HbA1c

Weight loss interventions made little or no difference to HbA1c when compared to diet comparators (Analysis 2.10 (2 studies, 163 CKD participants): MD ‐1.62%, 95% CI ‐3.87 to 0.63: I² = 89%). Jesudason 2013 reported HbA1c reduced by 0.3% (equivalent to 2 mmol/mol) across both diet study groups, with no difference observed between the two diet groups.

2.10. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 10: HbA1c

Fasting blood glucose

Weight loss interventions had an uncertain effects on fasting blood glucose levels compared to usual care or control (Analysis 1.11 (2 studies, 98 CKD participants): MD ‐1.27 mg/dL, 95% CI ‐2.66 to 0.11: I² = 0%). Teplan 2002 reported a combined diet and pharmacological intervention years in transplant recipients significantly reduced fasting blood glucose from 7.6 mmol/L to 5.2 mmol/L at three years, however comparison data was not reported to allow for data pooling.

1.11. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 11: Fasting glucose

Data from Jesudason 2013 and DIRECT 2013 comparing weight loss interventions to dietary intervention could not be pooled however, both found no difference in fasting blood glucose between the two groups.

Hypoglycaemic medication changes

Three studies reported on hypoglycaemic medication changes with uncertain effects.

• Orazio 2011 reported no difference between any weight loss intervention compared to usual care or control with regard to the use of metformin and insulin after a 2‐year follow‐up however, more participants in the lifestyle intervention group compared with control group were on a thiazolidinedione (25% versus 0%).

• Jesudason 2013 reported a variety of changes in hypoglycaemic medication use between two dietary study arms.

• MacLaughlin 2014 reported daily mean insulin dose differed by ‐36 units (95% CI ‐69 to 23) in the surgical versus non‐surgical group who received individualised diet and exercise program with concurrent prescription of orlistat.

Total cholesterol

Weight loss interventions made little or no difference to total cholesterol compared with usual care (Analysis 1.12 (6 studies, 169 participants): MD ‐9.07 mg/dL, 95% CI ‐20.31 to 2.18: I² = 0%). Teplan 2002 reported a significant reduction in total cholesterol at 3 years in transplant recipients from 6.9 mmol/L to 5.2 mmol/L, however comparison data was not reported to allow for data pooling.

1.12. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 12: Total cholesterol

Any weight loss intervention made little or no difference to total cholesterol compared with dietary interventions (Analysis 2.13 (4 studies, 272 participants): MD ‐2.01 mg/dL, 95% CI ‐21.38 to 17.35: I² = 73%). This finding was robust despite which of the 3 different dietary arms were rotated through the meta‐analysis from DIRECT 2013.

2.13. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 13: Total cholesterol

Stage of chronic kidney disease

There was little of no difference in total cholesterol following any weight loss intervention compared to usual care in either participants with CKD stages 1 to 4 or in transplant recipients (Analysis 4.2).

4.2. Analysis.

Comparison 4: Weight loss intervention versus usual care or control: stage of CKD, Outcome 2: Total cholesterol

Intervention duration

Weight loss interventions given for either less than 3 months or 3 months or more made little or no difference to total cholesterol (Analysis 5.3).

5.3. Analysis.

Comparison 5: Weight loss intervention versus usual care or control: duration of intervention, Outcome 3: Total cholesterol

Low density lipoprotein cholesterol

Weight loss intervention probably leads to a reduction in LDL cholesterol compared with usual care or control (Analysis 1.13 (4 studies, 139 participants): MD ‐10.30 mg/dL, 95% CI ‐16.70 to ‐3.90: I² = 0%). Teplan 2002 reported a reduction in total cholesterol at 3 years in transplant recipients from 4.1 mmol/L to 3.0 mmol/L, however comparison data was not reported to allow data pooling.

1.13. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 13: LDL cholesterol

Any weight loss intervention made little or no difference to LDL cholesterol compared with dietary interventions (Analysis 2.14 (4 studies, 272 participants): MD 1.39 mg/dL, 95% CI ‐16.66 to 19.45: I² = 72%). This finding was robust despite which of the 3 different dietary arms were rotated through the meta‐analysis from DIRECT 2013.

2.14. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 14: LDL cholesterol

High density lipoprotein cholesterol

There was no effect little or no difference in HDL cholesterol with any weight loss intervention compared to usual care or control (Analysis 1.14 (4 studies, 139 participants): MD 2.20 mg/dL, 95% CI ‐2.64 to 7.04: I² = 41%).

1.14. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 14: HDL cholesterol

Any weight loss intervention may reduce HDL cholesterol compared with dietary interventions (Analysis 2.15 (2 studies, 131 participants): MD ‐4.80 mg/dL, 95% CI ‐8.71 to ‐0.89; I² = 0%).

2.15. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 15: HDL cholesterol

Triglycerides

Any weight loss intervention compared to usual care or control had uncertain effects on serum triglycerides (Analysis 1.15 (5 studies, 156 CKD participants): MD ‐24.61 mg/dL, 95% CI ‐49.53 to 0.31: I² = 43%). Two other studies in transplant recipients reported mixed results however, they did not report appropriate data for pooling. Teplan 2002 reported a reduction in triglycerides at 3 years from 3.8 mmol/L to 2.3 mmol/L. In contrast, Tomlinson 1975 did not report any change in triglycerides following a pharmacological intervention compared to placebo.

1.15. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 15: Triglycerides

In studies comparing any weight loss intervention to dietary interventions, any weight loss intervention made little or no difference to triglycerides (Analysis 2.16 (4 studies, 272 participants): MD ‐3.22 mg/dL, 95% CI ‐31.50 to 25.06: I² = 47%). DIRECT 2013 reported no difference in triglycerides when comparing the effects of low‐carbohydrate, low‐fat and the Mediterranean diet. Leehey 2016 also reported no difference in triglycerides when comparing a combined energy‐restricted and exercise intervention to an energy‐restricted diet alone (Analysis 2.16). Teplan 2006 did however report the potential efficacy of one particular diet compared to another, showing a low protein and energy restricted diet with concurrent keto‐amino acid supplementation reduced serum triglycerides compared to low protein and energy restricted diet alone in CKD participants (Analysis 2.16).

2.16. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 16: Triglycerides

Lipid lowering medication changes

Orazio 2011 reported that after a 2‐year follow‐up, more patients in the lifestyle intervention group were on a statin than those in the control group, 96% versus 80% respectively.

Successful kidney transplantation

None of the included studies reported successful kidney transplantation.

Inflammation (C‐reactive protein)

Baria 2014 and Leehey 2009 both reported no effect of any weight loss intervention on C‐reactive protein compared to usual care.

Leehey 2016 found no effect of combined diet and exercise weight loss intervention on C‐reactive protein compared to a diet‐only intervention.

MacLaughlin 2014 reported no effect of a surgical intervention (sleeve gastrectomy) on C‐reactive protein compared to best medical care (individualised dietary and physical activity prescription combined with orlistat prescription) in obese patients with CKD stages 3 to 4.

Adherence to treatment

Jesudason 2013 reported the moderate protein group increased their protein intake to 1.22 g/kg/day and the standard protein group decreased their protein intake to 0.93 g/kg/day.

Ikizler 2018 reported all participants except one were within 20% of their assigned daily energy intake, and 70% of participants achieved an energy restriction lower than their assigned daily target.

LANDMARK 3 2013 reported an adherence of 70% to supervised gym training sessions in the intervention group. Leehey 2016 reported an attendance of 42% and 34% for lifestyle modification classes in the dietary group and exercise + diet group, respectively.

In surgical interventions versus non‐surgical interventions MacLaughlin 2014 reported a similar level of adherence with the best medical care group reporting four of the six patients (67%) attended over 90% of lifestyle program visits and all four were compliant, one was partially compliant and one non‐compliant with both the dietary and exercise interventions up to six months. MacLaughlin 2014 reported adherence with the initial liquid diet post‐surgery was 80% and 100% of patients continued to eat in accordance with the prescribed texture modification for three months and prescribed energy restriction up to 12 months.

Health‐related quality of life

Leehey 2016 did not find a combined diet and exercise weight loss intervention to improve overall QoL (as measured by The Short Form (36) Health Survey (SF‐36) compared to CKD participants receiving a diet‐only intervention.

MacLaughlin 2014 found significant improvements in the physical domain of the SF‐36 questionnaire in CKD participants who received a sleeve gastrectomy compared to patients receiving an individualised diet and exercise program with concurrent prescription of orlistat.

Nutritional status

None of the included studies reported the nutritional status of participants.

Dietary intake

Compared to usual care or control, weight loss interventions made little or no difference to changes in dietary energy intake (Analysis 1.17 (4 studies, 100 CKD participants): SMD ‐0.55, 95% CI ‐1.35 to 0.25: I² = 70%).

1.17. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 17: Dietary energy intake

• Two of these studies (Baria 2014; Leehey 2009) were exercise‐only interventions with no changes to dietary energy intake prescribed.

• LANDMARK 3 2013 involved a combined dietary and exercise intervention found no difference in energy intake between groups post intervention

• Kittiskulnam 2014 study which involved an energy restricted dietary only intervention reported a significant reduction in energy intake post intervention in the intervention group compared to the control group.

• Orazio 2011 reported median end‐of study values in transplant recipients which could not be pooled, reported a combined diet and exercise intervention to reduced overall daily energy intake by 1293 kJ compared to usual care.

• Jesudason 2013 reported a non‐significant difference in overall energy intake following a standard protein energy restricted diet compared to a moderate protein energy restricted diet, with overall energy intakes of 6200 kJ and 6500 kJ at the end of the 12 month study, respectively.

Intervention duration

Weight loss interventions given for either less than 3 months or 3 months or more made little or no difference to dietary intake (Analysis 5.4).

5.4. Analysis.

Comparison 5: Weight loss intervention versus usual care or control: duration of intervention, Outcome 4: Dietary energy intake

Physical activity behaviours

Orazio 2011 reported simple provision of advice and regular encouragement to increase levels of physical activity as part of a lifestyle intervention did not lead to improved physical activity behaviours compared to usual care. They reported no change in physical activity time for the intervention compared to the usual care group nor any difference between the two groups ability to meet Australian physical activity guidelines of 150 minutes of moderate intensity activity per week.

Cost per disability‐adjusted life years or quality‐adjusted life years

None of the included studies reported cost per DALYs or QALYs events.

Cost associated with weight loss intervention

None of the included studies reported on cost associated with weight loss interventions.

Adverse events and potential harms

Five studies reported on adverse outcomes associated with their weight loss intervention. Adverse effects reported included depression and diarrhoea, hypotension, musculoskeletal injuries, and hospitalisations. No studies reported on biochemical adverse effects such as hyperkalaemia or hyperphosphataemia.

• Leehey 2016 reported no study‐related adverse events in lifestyle (combined exercise and diet) group nor the diet only group.

• Ikizler 2018 reported seven study‐related adverse events with six of those happening in the aerobic exercise and caloric restriction group (atrial fibrillation requiring hospitalisation (1), hypotension due to weight loss (2), chest pain during exercise (1), musculoskeletal injuries (2)). A further episode of hypotension due to weight loss was reported in the usual activity and caloric restriction group. No study‐related adverse events were reported in the usual activity and usual diet group or in the aerobic exercise and usual diet group.

• Pharmacological interventions

  • Tomlinson 1975 reported fenfluramine had no effect of allograft function however some participants experienced diarrhoea and depression.

  • MacLaughlin 2014 reported orlistat was well tolerated in amongst participants, with few episodes of diarrhoea occurring during the first one to two months only and reported no incidence of AKI or oxalate nephropathy.

• Surgical interventions

  • Tzvetanov 2015 reported no surgical or medical complications related to the combined bariatric surgery and kidney transplantation. Participants in the intervention arm presented with no difficulties in maintaining immunosuppression, as well as no episodes of acute cellular or antibody mediated rejection.

  • MacLaughlin 2014 reported two hospital re‐admissions with dehydration within 30 days post‐surgery amongst participants who underwent sleeve gastrectomy.

Subgroup analyses

We did not perform subgroups analyses for BMI (overweight versus obese), chief causes of CKD, (diabetes, hypertension, glomerulonephritis, polycystic kidney disease, reflux kidney disease) and presence or absence of proteinuria because there were not enough studies to estimate effects in these subgroups.

Sensitivity analyses

We did not perform any sensitivity analyses because there were not enough studies included in the analyses.

Assessment of reporting bias

We did not draw funnel plots due to limited number of studies per outcome.

Discussion

Summary of main results

This systematic review summarises 17 studies (988 participants) examining the effect of weight loss interventions (lifestyle, pharmacological and surgical) for the treatment of overweight and obesity in adults with CKD. Included studies had a median study duration of 12 months (range 5 weeks to 3 years). Majority of studies (13) examined lifestyle weight loss interventions (dietary, exercise and or dietary and exercise combined) compared to usual standard care or other dietary weight loss interventions. Only two small studies (17 participants) included surgical weight loss interventions. The included studies involved people with CKD stages 1 to 4 (n = 620) and kidney transplant recipients (n = 368). There were no studies that investigated weight loss interventions for people with ESKD requiring dialysis or those choosing supportive care management. Interventions and comparators varied across the included studies. The studies were separated into three main groups for comparison: Any weight loss interventions versus usual care or control (main comparator), any weight loss intervention versus dietary intervention, and surgical intervention versus non‐surgical intervention. The risk of bias in the included studies were often unclear or high, and when combined with considerable heterogeneity in weight loss interventions and imprecision in effect estimates, led to low or very low confidence in the results.

None of the included studies were designed to evaluate the effects of weight loss interventions on death or cardiovascular events. As a result, whether weight loss interventions can lower the risk of death or cardiovascular events remains unanswered. This finding has important implications as people with all stages of CKD experience high levels of death and morbidity from CVD.

Overall, weight loss interventions (involving predominately lifestyle interventions) were more successful than the usual care or control comparators in reducing body weight, however had uncertain effects for other anthropometric measures including BMI, waist circumference, waist‐to‐hip ratio, and measures of fat mass. The effect of any weight loss interventions (all studies were non‐surgical interventions) was not superior to dietary only intervention comparators for weight loss. One study looking at surgical intervention compared to non‐surgical intervention found a greater reduction in weight loss, BMI, waist circumference and fat mass than the combined lifestyle and pharmacological comparator.

The effects of weight loss interventions on clinical measures across all comparators were infrequently measured limiting the ability of studies to be combined and reducing the overall quality of the evidence. Compared to usual standard care or control there were improvements in some, but not all clinical parameters. Improvements were found in LDL cholesterol; uncertain effects were found on CrCl, SCr, proteinuria, SBP, DBP, fasting blood glucose, HbA1c, and triglycerides; and no significant effect was found on total cholesterol, HDL cholesterol, and C‐reactive protein. There was limited reporting of adherence to treatment, adverse events, and potential harms across all three comparisons. The interventions that did report on these measures reported no major medical complications or serious adverse events with lifestyle, pharmacological or surgical weight loss interventions. A number of other secondary outcomes including successful kidney transplantation, nutritional status, biochemical adverse effects such as hyperkalaemia or hyperphosphataemia, cost associated with weight loss intervention, and cost effectiveness (per DALYs or QALY) were not measured in any of the included studies. Overall, the data from this review suggests that current evidence for weight loss interventions in overweight and obese individuals with CKD is limited and of very low to low quality and may be insufficient to guide clinical practice.

Overall completeness and applicability of evidence

This review examined 17 studies assessing the effects of lifestyle, pharmacological and surgical weight loss interventions in overweight and obese people with CKD. The strengths of the review include a comprehensive review of all types of weight loss interventions in CKD in both overweight and obese adults in all stages of CKD and limiting our review to RCTs and quasi‐RCTs. The majority of included studies involved lifestyle interventions with small numbers, with heterogeneous interventions and outcome measures, making comparison difficult. We could not assess the effect of weight loss interventions on important endpoints such as death or cardiovascular events, as none of the included studies in this review were designed to measure these outcomes. While all included studies reported on at least one anthropometric measure, there was inconsistent reporting for most clinical parameters, and limited to no reporting of patient‐centred outcomes, economic analysis and adverse events and potential harms. Due to within study heterogeneity we could not determine the effect of weight loss interventions on SCr and CrCl. There were four studies with mixed populations of CKD stages 1 to 4 (Jesudason 2013; Kittiskulnam 2014; Morales 2003a; Praga 1995) that included participants with hyperfiltration and reduced kidney function (eGFR) at baseline in the same treatment groups. These studies did not account for the different direction of change in which CrCl and SCr with weight loss in those with hyperfiltration (improvement via a reduction) versus those with a reduced eGFR (improvement via an increase). We found no differences in daily energy intake post intervention in lifestyle interventions versus usual care or control, as the majority of studies included in this sub‐analysis were exercise based interventions and did not prescribe a reduction in energy intake. Subgroup analyses were not able to be performed for many outcomes as often less than two studies reported the same outcome measures. Reporting on a set of core outcome measures for weight loss interventions in people with CKD would be helpful in future research studies to improve the quality of evidence.

Only two studies with very small sample sizes reported on surgical interventions with limited reporting on our outcomes of interest. Therefore, the benefits reported in these surgical intervention studies must be confirmed in larger studies to improve the quality and certainty of evidence to better guide clinical practice. None of the included studies involved participants undergoing dialysis treatment or supportive care management. Therefore, the results from this review may not be generalisable to these population groups. Further studies are therefore warranted to examine the effects of weight loss interventions in these population groups.

Quality of the evidence

The overall certainty of evidence for reported outcomes was very low. We downgraded the evidence for uncertain or high risk of bias, inconsistency, indirectness, and imprecision. Meta‐analysis was also difficult due to inconsistent reporting of outcome measures and significant heterogeneity in the characteristics of interventions. Key methodological limitations including risk of bias led to downgrading of all evidence by one level (high to moderate). Methods for interventions were insufficiently reported by most studies. The relative impact of lifestyle intervention on most outcomes (aside from waist circumference) was downgraded due to moderate to high statistical heterogeneity, leading to low certainty of evidence. Weight management interventions varied widely, including diet, diet and physical activity, physical activity alone, diet and pharmacotherapy, and weight loss surgery. Furthermore the control or comparator interventions were also varied, making direct comparisons difficult. Finally, due to the small sample size and often small number of included studies the results were imprecise, further compounding the uncertainty of evidence.

Potential biases in the review process

Potential biases in this review relate to the data availability in the individual studies, and heterogeneity in treatment intervention and comparisons. Additionally, sensitivity analyses could not be performed and reporting bias could not be assessed due to the limited number of included studies. Finally, treatment endpoints were surrogate markers of health (proteinuria, SBP and DBP) and the effects of weight loss interventions on longer term outcomes such as death and cardiovascular events remains uncertain. Study authors were contacted to provide additional information in an attempt to reduce potential bias (see Appendix 3 for additional information requested and provided by authors).

The strength of this review is that it included an up‐to‐date and comprehensive review of previous publications through a thorough MEDLINE, EMBASE and CENTRAL search and only included RCTs or quasi RCTs, as pre‐specified. Data extraction, data analysis and quality assessment were performed by two independent investigators, and any differences in consensus were checked with an additional author. It should be noted that there is potential conflict of interest as author HM was the principal investigator and co‐author of MacLaughlin 2014 study and KC is a co‐author of LANDMARK 3 2013 study both studies were included in this review. Authors MC, DJ, and KC work at the same facility where Orazio 2011 and LANDMARK 3 2013 were undertaken.

Agreements and disagreements with other studies or reviews

Our finding of a decrease in BMI with dietary interventions compared to control or usual care agree with a previous systematic review reporting pooled results from studies of non‐dialysis CKD and in participants with hyperfiltration (Navaneethan 2009). Other systematic reviews of outcomes of weight loss interventions in CKD populations did not report pooled effects, however all included studies demonstrated significant decreases in body mass or BMI within intervention groups but did not compare weight or BMI differences between groups (Afshinnia 2010; Bolignano 2013).

The effect of weight loss interventions on proteinuria was uncertain in lifestyle interventions and was not reported in studies of surgical interventions. This contrasts with previous findings reported by Navaneethan 2009, and Afshinnia 2010, with significant reductions in proteinuria. However both studies pooled only within group differences for intervention groups from observational studies and controlled studies and did not include comparisons with controls. This indicates that contrary to findings from observational studies, weight loss may not induce a reduction in proteinuria with moderate weight loss achieved with lifestyle interventions. However, one study included in the meta‐analysis compared diet induced weight loss with captopril, and found both equally effective at reducing proteinuria, which increases the bias towards a null finding. We found no change in albuminuria, and this is supported by the findings of Bolignano 2013 who reported two RCTs with no change in albuminuria, and a reduction in proteinuria or albuminuria in observational studies.

Measures of creatinine did not change with weight loss in either lifestyle or surgical interventions. This is similar to the findings of Navaneethan 2009 and Van Huffel 2014, also reporting no change in these measures with weight loss. We were unable to evaluate the effect of weight loss on measured GFR. Measured GFR was examined in two studies with low protein diet treatment arms, and showed a small improvement, however one of these studies did not achieve weight loss, limiting the applicability of the findings to the effects of intentional weight loss. Low density lipoprotein cholesterol decreased and the effect of weight loss on total cholesterol and triglycerides was uncertain. Navaneethan 2009 reported a decrease in total cholesterol with weight loss, and no change in HDL cholesterol or triglycerides within weight loss treatment groups.

Authors' conclusions

Implications for practice.

In the context of mild to moderate CKD, and post kidney transplantation, lifestyle‐based weight loss interventions may result in weight loss and may have positive effects on DBP and LDL cholesterol. No particular dietary intervention was superior to another; therefore it is likely that energy deficit remains key, and dietary interventions or mixed lifestyle interventions demonstrated more positive effects that exercise interventions alone. Evidence from RCTs for interventions using surgical interventions is lacking. We are unable to say whether weight loss interventions have an effect on proteinuria, CrCl or measured GFR.

Presently, it is recommended that the selection of weight loss interventions should be individualised, based not only on an assessment of the risks and benefits of individual weight loss intervention procedures and the level of kidney function, but also in combination with thorough consideration of patient preferences, motivations, confidence, and previous experience with weight loss interventions.

Implications for research.

Long‐term RCTs assessing the effect of intentional weight loss interventions (lifestyle, pharmacological and surgical) on death, cardiovascular events and on kidney outcomes such as measured GFR, CKD progression, development of ESKD, and successful transplantation in people with all stages of kidney disease are needed. It is also important that all future studies in this area are designed to and report on a standardised set of clinical, patient‐centred, economic and safety outcome measures including reporting on mean difference of these outcome measures so that future meta‐analysis can be conducted with a higher level and certainty of evidence.

History

Protocol first published: Issue 9, 2018
Review first published: Issue 3, 2021

Appendices

Appendix 1. Electronic search strategies

Database	Search terms
CENTRAL	MeSH descriptor: [Kidney Diseases] explode all trees MeSH descriptor: [Renal Replacement Therapy] explode all trees MeSH descriptor: [Renal Insufficiency] explode all trees MeSH descriptor: [Renal Insufficiency, Chronic] explode all trees dialysis:ti,ab,kw (Word variations have been searched) hemodialysis or haemodialysis:ti,ab,kw (Word variations have been searched) hemofiltration or haemofiltration:ti,ab,kw (Word variations have been searched) hemodiafiltration or haemodiafiltration:ti,ab,kw (Word variations have been searched) kidney disease* or renal disease* or kidney failure or renal failure:ti,ab,kw (Word variations have been searched) ESRF or ESKF or ESRD or ESKD:ti,ab,kw (Word variations have been searched) CKF or CKD or CRF or CRD:ti,ab,kw (Word variations have been searched) CAPD or CCPD or APD:ti,ab,kw (Word variations have been searched) predialysis or pre‐dialysis:ti,ab,kw (Word variations have been searched) {or #1‐#13} MeSH descriptor: [Weight Loss] this term only MeSH descriptor: [Weight Reduction Programs] this term only MeSH descriptor: [Body Weight] this term only MeSH descriptor: [Body Weight Changes] explode all trees MeSH descriptor: [Anti‐Obesity Agents] explode all trees MeSH descriptor: [Diet Therapy] explode all trees MeSH descriptor: [Energy Intake] explode all trees MeSH descriptor: [Behavior Therapy] explode all trees MeSH descriptor: [Food, Formulated] explode all trees calorie control*:ti,ab,kw (Word variations have been searched) calorie restrict*:ti,ab,kw (Word variations have been searched) weight loss:ti,ab,kw (Word variations have been searched) meal replacement*:ti,ab,kw (Word variations have been searched) weight reduc*:ti,ab,kw (Word variations have been searched) MeSH descriptor: [Exercise] explode all trees MeSH descriptor: [Exercise Therapy] explode all trees MeSH descriptor: [Gastric Bypass] this term only MeSH descriptor: [Gastroplasty] this term only gastric band*:ti,ab,kw (Word variations have been searched) gastric bypass:ti,ab,kw (Word variations have been searched) laparoscopic sleeve gastrectom*:ti,ab,kw (Word variations have been searched) {or #15‐#35} MeSH descriptor: [Obesity] explode all trees MeSH descriptor: [Overweight] this term only overweight*:ti,ab,kw (Word variations have been searched) obese or obesity:ti,ab,kw (Word variations have been searched) {or #37‐#40} {and #14, #36, #41}
MEDLINE	Kidney Diseases/ exp Renal Replacement Therapy/ Renal Insufficiency/ exp Renal Insufficiency, Chronic/ Diabetic Nephropathies/ exp Hypertension, Renal/ dialysis.tw. (hemodialysis or haemodialysis).tw. (hemofiltration or haemofiltration).tw. (hemodiafiltration or haemodiafiltration).tw. (kidney disease* or renal disease* or kidney failure or renal failure).tw. (ESRF or ESKF or ESRD or ESKD).tw. (CKF or CKD or CRF or CRD).tw. (CAPD or CCPD or APD).tw. (predialysis or pre‐dialysis).tw. or/1‐15 Weight Loss/ body weight changes/ Body Weight/ Weight Reduction Programs/ exp Anti‐Obesity Agents/ exp Diet Therapy/ exp Energy Intake/ exp Behavior Therapy/ exp Food, Formulated/ calorie controlled.tw. calorie restrict$.tw. diet$.tw. weight loss.tw. weight reduc$.tw. meal replacement$.tw. exp Exercise/ exp Exercise Therapy/ Gastric Bypass/ Gastroplasty/ gastric band$.tw. gastric bypass.tw. laparoscopic sleeve gastrectom$.tw. or/17‐38 exp Obesity/ Overweight/ Body Weight/ overweight.tw. (obese or obesity).tw. or/41‐45 and/16,39,45
EMBASE	exp renal replacement therapy/ kidney disease/ chronic kidney disease/ kidney failure/ chronic kidney failure/ mild renal impairment/ stage 1 kidney disease/ moderate renal impairment/ severe renal impairment/ end stage renal disease/ renal replacement therapy‐dependent renal disease/ diabetic nephropathy/ kidney transplantation/ renovascular hypertension/ (hemodialysis or haemodialysis).tw. (hemofiltration or haemofiltration).tw. (hemodiafiltration or haemodiafiltration).tw. dialysis.tw. (CAPD or CCPD or APD).tw. (kidney disease* or renal disease* or kidney failure or renal failure).tw. (CKF or CKD or CRF or CRD).tw. (ESRF or ESKF or ESRD or ESKD).tw. (predialysis or pre‐dialysis).tw. ((kidney or renal) adj (transplant* or graft* or allograft*)).tw. or/1‐24 weight reduction/ weight loss program/ body weight management/ antiobesity agent/ diet therapy/ or diet restriction/ or low calory diet/ or low fat diet/ or protein diet/ (calorie controlled or calorie restrict$).tw. weight loss.tw. weight reduc$.tw. meal replacement$.tw. exp exercise/ exp kinesiotherapy/ stomach bypass/ gastric band/ gastric banding/ sleeve gastrectomy/ laparoscopic sleeve gastrectom$.tw. or/26‐41 obesity/ or abdominal obesity/ or morbid obesity/ overweight.tw. or/43‐44 and/25,42,45

Appendix 2. Risk of bias assessment tool

Potential source of bias	Assessment criteria
Random sequence generation Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence	Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimisation (minimisation may be implemented without a random element, and this is considered to be equivalent to being random).
	High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
	Unclear: Insufficient information about the sequence generation process to permit judgement.
Allocation concealment Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment	Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web‐based, and pharmacy‐controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).
	High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
	Unclear: Randomisation stated but no information on method used is available.
Blinding of participants and personnel Performance bias due to knowledge of the allocated interventions by participants and personnel during the study	Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
	High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
	Unclear: Insufficient information to permit judgement
Blinding of outcome assessment Detection bias due to knowledge of the allocated interventions by outcome assessors.	Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
	High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.
	Unclear: Insufficient information to permit judgement
Incomplete outcome data Attrition bias due to amount, nature or handling of incomplete outcome data.	Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.
	High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.
	Unclear: Insufficient information to permit judgement
Selective reporting Reporting bias due to selective outcome reporting	Low risk of bias: The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon).
	High risk of bias: Not all of the study’s pre‐specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. sub‐scales) that were not pre‐specified; one or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.
	Unclear: Insufficient information to permit judgement
Other bias Bias due to problems not covered elsewhere in the table	Low risk of bias: The study appears to be free of other sources of bias.
	High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data‐dependent process (including a formal‐stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.
	Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.

Appendix 3. Survey of authors providing information on included trials

Characteristic	Study author contacted	Study author replied	Study author asked for additional information	Study author provided data
	Date	Date	Short summary	Short summary
Baria 2014	Yes 07/01/2020 & 14/01/2020	No	Study start and finish dates and asked if outcome assessors for all outcome measures blinded	No response received
DIRECT 2013	Yes 07/0/2020 & 20/01/2020	Yes 20/01/20	Requested subgroup baseline and post intervention mean and SD for those only with stage 3 CKD eGFR 30 to 60 mL/min/1.73 m²	Baseline and post intervention mean and SD values for body weight, BMI, waist circumference, SBP and DBP, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and fasting plasma glucose levels for all 3 dietary intervention groups were provided
Jesudason 2013	Yes 14/01/2020	Yes 15/01/20	Requested post intervention mean and SD body weight baseline daily energy intake, post intervention albuminuria, baseline and post intervention SBP, post intervention HbA1C, and baseline and post intervention body fat mass and lean mass for both dietary groups	Requested data provided
Kittiskulnam 2014	Yes 14/01/2020	No	Enquired as to whether baseline and post intervention energy intakes were calculated from participants seven day food records and if so asked if this data could be sent	No response received
LANDMARK 3 2013	Yes 16/01/20	Yes	Requested sub‐study data for those in study who were overweight or obese	Author responded was unable to provide sub‐study data
Leehey 2009	Yes 14/01/2020 & 28/01/2020	No	Post intervention (12 weeks and 52 weeks) body weight (kg) mean and SD for all groups	No response received
MacLaughlin 2014	Yes 07/01/2020	Yes 21/01/20	Requested post intervention body weight, BMI, waist circumference, serum creatinine, proteinuria, SBP, DBP, and C‐reactive protein	Requested data provided
Orazio 2011	Yes 16/01/20	Yes	Requested sub‐study data for those in study who were overweight or obese	Author responded was unable to provide sub‐study data
Tzvetanov 2014	Yes 27/12/2019 & 19/01/2020	No	Asked author if they had published any further data with more numbers as report included was an abstract only	No response received
Teplan 2006 Teplan 2002	Yes 29/12/2019 20/01/2020	No	Whether multiple reports were from the same study. Asked to describe randomisation and allocation processes that were used to allocated participants to groups	No response received
Woolf 2017	Yes 22/02/20	No	Requested more detailed information on inclusion, exclusion criteria, information on study procedures, whether more data is published elsewhere and whether study is part of a large trial	No response received

Appendix 4. Summary of included studies

Intervention Study ID	Intervention	Comparator	CKD stage	Mean age (years)	Men (%)	Mean BMI (kg/m²)	Length of intervention	Description of intervention and comparator	Primary outcome/s
Comparison 1. Lifestyle Interventions versus usual care or control
Lifestyle Interventions versus usual care or control
Baria 2014	Exercise	Usual care	Stages 3 to 4	52	100	30.4 ± 3.8	12 weeks	Intervention (n =8) Centre based aerobic exercise: 3 x 30 minute walking sessions/week on in centre treadmill, increasing intensity and duration Home based aerobic exercise: 3 x 30 minute walking sessions/week at home, increasing intensity and duration Comparison (n = 9) Usual care: no exercise intervention	Body composition (weight loss, BMI, waist circumference, visceral fat, subcutaneous fat)
Ikizler 2018	Dietary and aerobic exercise	Usual care Dietary Exercise	Stages 3 to 4	60	68	‐	4 months	Intervention x 3 (n = 71) Aerobic exercise + energy restriction (n = 24): supervised aerobic exercise x 3; 30 to 45 minute sessions/week + daily dietary restriction of 300 to 500 kcal OR Usual activity + energy restriction (n = 25): usual activity + daily energy restriction of 300 to 500 kcal OR Aerobic exercise + usual diet (n = 22): supervised aerobic exercise x 3; 30 to 45 minute sessions/week + usual diet Comparison (n = 21) Usual activity + usual diet: advised to continue with usual diet and usual activity	Metabolic risk profile (oxidative stress, inflammation, and body composition (BMI, waist circumference, body fat)
Kittiskulnam 2014	Dietary	Usual care	Stages 1 to 4	45	85	Diet‐group 28.5 ± 4.8 Usual care 28.7 ± 4.8	6 months	Intervention(n = 13) Daily energy restriction of 500 kcal + daily protein target of 0.6 to 0.8 g/kg/day Comparison(n = 13) No energy restriction Usual care: dietary advice to retard CKD progression with goal for protein target of 0.6 to 0.8g/kg/day	Proteinuria, adipokine level, renal function (eGFR, serum creatinine)
LANDMARK 3 2013	Mixed (dietary and exercise and behavioural)	Usual care	Stages 3 to 4	Intervention 60 Control 62	63	Intervention 32.5 ± 6.8 Control 33.0 ± 8.0	12 months	Intervention (n = 36) Lifestyle intervention included multidisciplinary care (including a CKD nurse practitioner, dietitian, exercise physiologist, diabetic educator, psychologist, and social worker), a lifestyle program, and aerobic and resistance exercise training Comparison (n = 36) Usual standard nephrologist care and referral to an allied health professional on an ad hoc basis.	Cardiorespiratory fitness ( peak V02)
Leehey 2009	Exercise	Usual care	Stages 2 to 4	66	100	‐	24 weeks	Intervention (n = 7) Aerobic exercise: 3 x 30 minute walking sessions/week, (6 weeks in‐centre, then 18 weeks at home) increasing intensity and duration Comparison (n = 4) Standard medical care including education for treatment of diabetes and CKD	Proteinuria
Morales 2003a	Dietary	Usual care	CKD stages 1 to 4	56	60	Diet‐group 33 ± 3.5 Usual care 34.3 ± 5.7	5 months	Intervention (n = 20) Daily energy restriction of 500 kcal + daily protein target of 1 to 1.2g/kg/day Comparison (n = 10) No energy restriction. Usual dietary intake with a protein goal of 1 to 1.2g/kg/day	Urinary protein excretion
Orazio 2011	Lifestyle	Usual care	Transplant recipients	55	61	Intervention group 29 ± 5 Control group 29 ± 6	2 years	Intervention (n = 56) Mediterranean style, low glycaemic index diet with a 500 kcal/day energy restriction and encouraged to achieve 150 minutes of accumulated physical activity each week with Health Behaviour Change or stage of Change Model underpinning the lifestyle intervention Comparison (n = 46) Standard usual care	Dietary factors, physical activity, cardiorespiratory fitness, anthropometry, biochemical and clinical factors
Praga 1995	Dietary	Usual care	CKD	48	35	37.9 ± 4.1	12 months	Intervention (n = 9) Energy restricted diet. 1000 to 1400 kcal/day without protein restrictions Comparison (n = 8) No energy restriction, maintained current dietary habits. Commenced captopril treatment (25 to 150 mg/day)	Weight loss, proteinuria
Woolf 2017	Behavioural ‐ Social Cognitive Theory (SCT) based counselling	Usual care	CKD	66	71	34.8 ± 5.4	6 months	Intervention (n = 7) SCT‐based live WebEx sessions with a registered dietitian, access to online tool to log dietary intake, exercise, and body weight and email feedback from a registered dietitian weekly for the first month and then biweekly for 6 months Comparison (n = 7) Standard behaviour management group. No further information on what the group received was reported	Weight loss and self efficacy
Pharmacological Interventions versus usual care or control
Tomlinson 1975 (Trial 2)	Appetite suppressant	Control	Transplant recipients	‐	57	‐	5 to 6 weeks	Intervention (n = 8) Received 80 mg/day fenfluramine for 5 to 6 weeks, then placebo medication for a period of 3 weeks and finally given placebo medication for 5 to 6 weeks Comparison (n = 6) Received placebo for 5 to 6 weeks, then placebo medication for a period of 3 weeks, and finally given 80 mg/day fenfluramine for 5 to 6 weeks	Body weight, plasma lipids
Mixed Interventions versus usual care or control
Teplan 2002	Dietary and appetite suppressant	Control	Transplant recipients	Range 22 to 78	42	‐	3 years	Intervention (n = 128) Individualised low energy and low fat diet + corticoids withdrawal. After 3 months participants were given orlistat at a dose of up to 3 x 120 mg/day and statins for 3 years Comparison (n = 130) Usual care for up to 3 years	BMI, total cholesterol, triglycerides, LDL cholesterol, fasting blood sugar level, creatinine clearance, proteinuria
Comparison 2. Any weight loss intervention versus diet intervention
DIRECT 2013	Dietary	Dietary	Subset data of those with stage 3 to 4 CKD obtained from authors	‐	‐	Low fat diet 30.8 ± 2.89 Mediterranean diet 30.6 ± 4.0 low carbohydrate diet 31.3 ± 3.24	2 years	Intervention 1 (n = 34) Low fat diet: 1500 kcal/day for women and 1800 kcal/day for men, 30% from total fat, 10% from saturated fat Intervention 2 (n = 36) Mediterranean energy restricted: 1500 kcal/day for women and 1800 kcal/day for men, goal no more than 35% of energy from fat, main sources of fat were 30 to 45 g of olive oil and a handful of nuts per day Intervention3 (n = 29) Low carbohydrate, non‐energy restricted: 20 g of carbohydrate/day for 2 months and then gradual increase to a max of 120 g/day	Weight loss
Jesudason 2013	Dietary	Dietary	CKD stage 1, 2 and those with stage 3 with an eGFR > 40	59.4	78	‐	12 months	Intervention 1 (n = 24) Standard protein weight loss diet: 6000 kJ for women and 7000 kJ/day for men, daily protein goal of 90 to 120 g Intervention 2 (n = 21) Moderate protein weight loss diet: 6000 kJ/day for women and 7000 kJ/day for men, daily protein goal of 90 to 120 g	Kidney function (measured GFR)
Leehey 2016	Exercise + dietary	Dietary	CKD stage 2 to 4	66	100	37.0 ± 4.5	12 months	Intervention 1 (n = 18) Exercise + dietary: 12 weeks of thrice weekly exercise training followed by 40 weeks of supervised home exercise + daily 200 to 250 kcal energy restriction and usual medical care Intervention 2 (n = 18) Diet only :daily 200 to 250 kcal energy restriction + usual medical care	Urine protein:creatinine ratio
Teplan 2006	Dietary	Dietary	CKD stage 3 to 4	52	49	Group 1 32.0 ± 3.3 Group 2 31.6 ± 3.9	3 years	Intervention 1 (n = 66) Low protein + energy restriction + keto‐amino acid supplementation: low protein diet 0.6 g/kg/day, energy intake 120 to 125 kJ/kg/day for first 6 months and 125 to 130 kJ/kg/day thereafter. Diet was supplemented with Ketosteril (Fresenius Kabi) at a dose of 100 mg/kg/day Intervention 2 (n = 65) Low protein + energy restriction + placebo: low protein diet 0.6 g/kg/day, energy intake 120 to 125 kJ/kg/day for first 6 months and 125 to 130 kJ/kg/day thereafter. Diet was supplemented with placebo	Plasma asymmetric dimethylarginine levels, body composition (BMI, visceral fat mass)
Tomlinson 1975 (Trial 1)	Appetite suppressant	Dietary	Transplant recipients	‐	55	‐	12 to 15 weeks	Intervention 1 (n = 6) Received placebo medication for 2 to 3 weeks as a run‐in period, then continued on placebo medication for 5 to 6 weeks followed by 120 mg/day fenfluramine for 5 to 6 weeks. Received dietary advice at the beginning and during the run in phase Intervention 2 (n = 5) Received placebo medication for 2 to 3 weeks as a run‐in period, then received 120 mg/day fenfluramine for 5 to 6 weeks followed by placebo medication for 5 to 6 weeks. Received dietary advice at the beginning and during the run in phase	Body weight, plasma lipids
Comparison 3. Surgical intervention versus non‐surgical intervention
MacLaughlin 2014	Surgical (sleeve gastrectomy)	Dietary + pharmacological	CKD 3 to 4	Median age 52	18	Median 39.5	12 months	Intervention (n = 5) Laparoscopic sleeve gastrectomy surgery + dietary energy restriction to ~ 1000 kcal/day post surgery Comparison (n = 6) Best medical care including an individualised dietary and physical activity prescription + orlistat	eGFR, proteinuria, quality of life, insulin resistance, inflammation, adipokine response
Tzvetanov 2015	Surgical (sleeve gastrectomy)	Standard weight loss program	Transplant recipients	Surgical group 45 Standard weight loss group 43	‐	Surgical group 39.9 ± 1.4 Standard weight loss group 40.5 ± 0.2	12 months	Intervention (n = 4) Simultaneous robotic kidney transplant and sleeve gastrectomy Comparison (n = 2) Standard weight loss program after a robotic kidney transplant	BMI, eGFR

Data and analyses

Comparison 1. Any weight loss intervention versus usual care or control.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Mean weight loss [kg] or post intervention body weight	6	180	Mean Difference (IV, Random, 95% CI)	‐3.69 [‐5.82, ‐1.57]
1.1.1 Lifestyle: dietary interventions (post intervention body weight)	2	56	Mean Difference (IV, Random, 95% CI)	‐7.73 [‐16.06, 0.59]
1.1.2 Lifestyle: physical activity (post intervention body weight)	2	38	Mean Difference (IV, Random, 95% CI)	‐6.32 [‐27.45, 14.81]
1.1.3 Lifestyle: mixed interventions (mean weight loss)	1	72	Mean Difference (IV, Random, 95% CI)	‐2.50 [‐4.33, ‐0.67]
1.1.4 Pharmacological interventions: appetite suppressant (mean weight loss)	1	14	Mean Difference (IV, Random, 95% CI)	‐2.53 [‐5.33, 0.27]
1.2 Body mass index	4	100	Mean Difference (IV, Random, 95% CI)	‐2.18 [‐4.90, 0.54]
1.2.1 Lifestyle: dietary interventions	3	73	Mean Difference (IV, Random, 95% CI)	‐3.36 [‐5.68, ‐1.04]
1.2.2 Lifestyle: physical activity	1	27	Mean Difference (IV, Random, 95% CI)	0.56 [‐1.90, 3.02]
1.3 Waist circumference	2	53	Mean Difference (IV, Random, 95% CI)	‐0.68 [‐7.60, 6.24]
1.3.1 Lifestyle: dietary interventions	1	26	Mean Difference (IV, Random, 95% CI)	‐4.60 [‐12.88, 3.68]
1.3.2 Lifestyle: physical activity	1	27	Mean Difference (IV, Random, 95% CI)	2.50 [‐4.45, 9.45]
1.4 Waist‐to‐hip ratio	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.4.1 Lifestyle: mixed interventions (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.5 Creatinine clearance [points]	3	58	Std. Mean Difference (IV, Random, 95% CI)	0.29 [‐0.34, 0.91]
1.5.1 Lifestyle: dietary interventions	2	47	Std. Mean Difference (IV, Random, 95% CI)	0.50 [‐0.11, 1.11]
1.5.2 Lifestyle: physical activity	1	11	Std. Mean Difference (IV, Random, 95% CI)	‐0.54 [‐1.80, 0.72]
1.6 Serum creatinine	4	84	Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.52, 0.22]
1.6.1 Lifestyle: dietary interventions	3	73	Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.62, 0.06]
1.6.2 Lifestyle: physical activity	1	11	Mean Difference (IV, Random, 95% CI)	0.70 [‐0.27, 1.67]
1.7 Proteinuria	4	84	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.76, 0.18]
1.7.1 Lifestyle: dietary interventions	3	73	Mean Difference (IV, Random, 95% CI)	‐0.52 [‐1.15, 0.12]
1.7.2 Lifestyle: physical activity	1	11	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.46, 0.46]
1.8 Systolic blood pressure	4	139	Mean Difference (IV, Random, 95% CI)	‐5.90 [‐13.75, 1.96]
1.8.1 Lifestyle: dietary interventions	2	56	Mean Difference (IV, Random, 95% CI)	‐2.06 [‐7.90, 3.78]
1.8.2 Lifestyle: physical activity	2	83	Mean Difference (IV, Random, 95% CI)	‐11.28 [‐30.93, 8.38]
1.9 Diastolic blood pressure	4	139	Mean Difference (IV, Random, 95% CI)	‐5.49 [‐11.13, 0.14]
1.9.1 Lifestyle: dietary interventions	2	56	Mean Difference (IV, Random, 95% CI)	‐5.59 [‐17.43, 6.26]
1.9.2 Lifestyle: physical activity	2	83	Mean Difference (IV, Random, 95% CI)	‐5.95 [‐14.78, 2.87]
1.10 HbA1c	2	83	Mean Difference (IV, Random, 95% CI)	‐0.48 [‐1.15, 0.18]
1.10.1 Lifestyle: physical activity	1	11	Mean Difference (IV, Random, 95% CI)	0.20 [‐3.84, 4.24]
1.10.2 Lifestyle: mixed interventions (change score)	1	72	Mean Difference (IV, Random, 95% CI)	‐0.50 [‐1.17, 0.17]
1.11 Fasting glucose	2	98	Mean Difference (IV, Random, 95% CI)	‐1.27 [‐2.66, 0.11]
1.11.1 Lifestyle: dietary interventions	1	26	Mean Difference (IV, Random, 95% CI)	5.20 [‐17.04, 27.44]
1.11.2 Lifestyle: mixed interventions (change score)	1	72	Mean Difference (IV, Random, 95% CI)	‐1.30 [‐2.69, 0.09]
1.12 Total cholesterol	6	169	Mean Difference (IV, Random, 95% CI)	‐9.06 [‐20.30, 2.19]
1.12.1 Lifestyle: dietary interventions	3	73	Mean Difference (IV, Random, 95% CI)	‐12.99 [‐31.29, 5.30]
1.12.2 Lifestyle: physical activity	1	11	Mean Difference (IV, Random, 95% CI)	‐8.00 [‐34.97, 18.97]
1.12.3 Lifestyle: mixed interventions (change score)	1	72	Mean Difference (IV, Random, 95% CI)	‐7.70 [‐25.58, 10.18]
1.12.4 Pharmacological interventions	1	13	Mean Difference (IV, Random, 95% CI)	14.10 [‐45.10, 73.30]
1.13 LDL cholesterol	4	139	Mean Difference (IV, Random, 95% CI)	‐10.30 [‐16.70, ‐3.90]
1.13.1 Lifestyle: dietary interventions	2	56	Mean Difference (IV, Random, 95% CI)	3.28 [‐16.47, 23.03]
1.13.2 Lifestyle: physical activity	1	11	Mean Difference (IV, Random, 95% CI)	‐15.00 [‐38.05, 8.05]
1.13.3 Lifestyle: mixed interventions (change score)	1	72	Mean Difference (IV, Random, 95% CI)	‐11.60 [‐18.68, ‐4.52]
1.14 HDL cholesterol	4		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.14.1 Lifestyle: dietary interventions	2		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.14.2 Lifestyle: physical activity	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.14.3 Lifestyle: mixed interventions	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.15 Triglycerides	5	156	Mean Difference (IV, Random, 95% CI)	‐24.61 [‐49.53, 0.31]
1.15.1 Lifestyle: dietary interventions	3	73	Mean Difference (IV, Random, 95% CI)	‐16.29 [‐65.23, 32.66]
1.15.2 Lifestyle: physical activity	1	11	Mean Difference (IV, Random, 95% CI)	‐46.00 [‐163.90, 71.90]
1.15.3 Lifestyle: mixed interventions (change score)	1	72	Mean Difference (IV, Random, 95% CI)	‐32.40 [‐39.58, ‐25.22]
1.16 C‐reactive protein	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.16.1 Lifestyle: physical activity	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.17 Dietary energy intake	4	100	Std. Mean Difference (IV, Random, 95% CI)	‐0.55 [‐1.35, 0.25]
1.17.1 Lifestyle: dietary interventions	1	26	Std. Mean Difference (IV, Random, 95% CI)	‐1.77 [‐2.70, ‐0.84]
1.17.2 Lifestyle: physical activity	2	38	Std. Mean Difference (IV, Random, 95% CI)	‐0.06 [‐0.73, 0.62]
1.17.3 Lifestyle: mixed interventions	1	36	Std. Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.86, 0.45]

1.4. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 4: Waist‐to‐hip ratio

1.16. Analysis.

Comparison 1: Any weight loss intervention versus usual care or control, Outcome 16: C‐reactive protein

Comparison 2. Any weight loss intervention versus dietary intervention.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Mean weight loss [kg] or post intervention body weight	3	155	Mean Difference (IV, Random, 95% CI)	0.76 [‐2.12, 3.64]
2.1.1 Low carbohydrate diet versus Mediterranean diet (post intervention body weight)	1	47	Mean Difference (IV, Random, 95% CI)	2.05 [‐6.23, 10.33]
2.1.2 Low fat diet versus Mediterranean diet (post intervention body weight)	1	52	Mean Difference (IV, Random, 95% CI)	2.88 [‐5.69, 11.45]
2.1.3 Moderate‐protein weight loss diet versus Standard‐protein weight loss diet (mean weight loss)	1	45	Mean Difference (IV, Random, 95% CI)	3.10 [‐3.30, 9.50]
2.1.4 Dietary advice + appetite suppressant (pharmacological) versus dietary advice alone (mean weight loss)	1	11	Mean Difference (IV, Random, 95% CI)	‐0.78 [‐4.61, 3.05]
2.2 Body mass index	3	262	Mean Difference (IV, Random, 95% CI)	‐1.27 [‐4.43, 1.89]
2.2.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	0.25 [‐1.97, 2.47]
2.2.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	0.39 [‐1.86, 2.64]
2.2.3 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1	131	Mean Difference (IV, Random, 95% CI)	‐4.80 [‐6.22, ‐3.38]
2.2.4 Energy restriction + exercise versus energy restriction alone	1	32	Mean Difference (IV, Random, 95% CI)	‐0.40 [‐4.65, 3.85]
2.3 Waist circumference	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.3.1 Low carbohydrate diet versus Mediterranean diet	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.3.2 Low fat diet versus Mediterranean diet	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.4 Waist‐to‐hip ratio	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.4.1 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.5 Creatinine clearance [mL/min/1.732]	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.5.1 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.6 Proteinuria	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.6.1 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.7 Measured GFR	2	176	Std. Mean Difference (IV, Random, 95% CI)	0.63 [0.25, 1.02]
2.7.1 Low protein weight loss diet + keto‐amino acids versus Low protein weight diet alone	1	131	Std. Mean Difference (IV, Random, 95% CI)	0.77 [0.42, 1.13]
2.7.2 Energy restricted low protein diet versus energy restricted moderate protein diet	1	45	Std. Mean Difference (IV, Random, 95% CI)	0.35 [‐0.24, 0.94]
2.8 Systolic blood pressure	3	262	Mean Difference (IV, Random, 95% CI)	‐2.33 [‐8.32, 3.67]
2.8.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	1.03 [‐5.94, 8.00]
2.8.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	‐1.23 [‐8.25, 5.79]
2.8.3 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1	131	Mean Difference (IV, Random, 95% CI)	‐8.00 [‐10.57, ‐5.43]
2.8.4 Energy restriction + exercise versus dietary energy restriction alone	1	32	Mean Difference (IV, Random, 95% CI)	4.00 [‐8.57, 16.57]
2.9 Diastolic blood pressure	3	275	Mean Difference (IV, Random, 95% CI)	‐1.87 [‐3.59, ‐0.14]
2.9.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐5.61, 4.77]
2.9.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	‐1.49 [‐6.72, 3.74]
2.9.3 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1	131	Mean Difference (IV, Random, 95% CI)	‐2.00 [‐4.09, 0.09]
2.9.4 Moderate protein weight loss diet versus standard protein weight loss diet	1	45	Mean Difference (IV, Random, 95% CI)	‐3.00 [‐8.55, 2.55]
2.10 HbA1c	2	163	Mean Difference (IV, Random, 95% CI)	‐1.62 [‐3.87, 0.63]
2.10.1 Energy restriction + exercise versus energy restriction alone	1	32	Mean Difference (IV, Random, 95% CI)	‐0.40 [‐1.73, 0.93]
2.10.2 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1	131	Mean Difference (IV, Random, 95% CI)	‐2.70 [‐3.45, ‐1.95]
2.11 Fasting blood glucose	1	99	Mean Difference (IV, Random, 95% CI)	‐2.56 [‐10.21, 5.08]
2.11.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	‐0.28 [‐11.27, 10.71]
2.11.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	‐4.71 [‐15.35, 5.93]
2.12 C‐reactive protein	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.12.1 Energy restriction + exercise versus energy restriction alone	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.13 Total cholesterol	4	272	Mean Difference (IV, Random, 95% CI)	‐2.01 [‐21.38, 17.35]
2.13.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	9.49 [‐11.10, 30.08]
2.13.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	‐0.61 [‐24.13, 22.91]
2.13.3 Low protein weight loss diet + keto‐amino acids versus low protein weight diet alone	1	131	Mean Difference (IV, Random, 95% CI)	‐23.20 [‐33.95, ‐12.45]
2.13.4 Energy restriction + exercise versus energy restriction alone	1	32	Mean Difference (IV, Random, 95% CI)	16.00 [‐6.75, 38.75]
2.13.5 Dietary advice + appetite suppressant (pharmacological) versus dietary advice alone	1	10	Mean Difference (IV, Random, 95% CI)	‐18.00 [‐94.25, 58.25]
2.14 LDL cholesterol	3	262	Mean Difference (IV, Random, 95% CI)	1.39 [‐16.66, 19.45]
2.14.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	7.31 [‐12.91, 27.53]
2.14.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	4.60 [‐15.88, 25.08]
2.14.3 Low protein weight loss diet + keto‐amino acids versus low protein weight diet	1	131	Mean Difference (IV, Random, 95% CI)	‐19.34 [‐32.58, ‐6.10]
2.14.4 Energy restriction + exercise versus energy restriction alone	1	32	Mean Difference (IV, Random, 95% CI)	20.00 [‐4.87, 44.87]
2.15 HDL cholesterol	2	131	Mean Difference (IV, Random, 95% CI)	‐4.80 [‐8.71, ‐0.89]
2.15.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	‐2.69 [‐9.11, 3.73]
2.15.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	‐5.09 [‐12.04, 1.86]
2.15.3 Energy restriction + exercise versus energy restriction alone	1	32	Mean Difference (IV, Random, 95% CI)	‐7.00 [‐13.98, ‐0.02]
2.16 Triglycerides	3	262	Mean Difference (IV, Random, 95% CI)	‐3.22 [‐31.50, 25.06]
2.16.1 Low carbohydrate diet versus Mediterranean diet	1	47	Mean Difference (IV, Random, 95% CI)	5.87 [‐49.06, 60.80]
2.16.2 Low fat diet versus Mediterranean diet	1	52	Mean Difference (IV, Random, 95% CI)	0.20 [‐46.75, 47.15]
2.16.3 Low protein weight loss diet + keto‐amino acids versus low protein weight diet	1	131	Mean Difference (IV, Random, 95% CI)	‐23.20 [‐37.84, ‐8.56]
2.16.4 Energy restriction + exercise versus energy restriction	1	32	Mean Difference (IV, Random, 95% CI)	49.00 [‐17.63, 115.63]
2.17 Dietary energy intake	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.17.1 Energyrestricted low protein versus energy restricted moderate protein	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.18 Quality of life: SF36 physical domain	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.18.1 Energy restriction + exercise versus energy restriction	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.19 Quality of life: SF36 mental domain	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.19.1 Energy restriction + exercise versus energy restriction	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.20 Quality of life: CES‐D	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.20.1 Energy restriction + exercise versus energy restriction	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

2.3. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 3: Waist circumference

2.4. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 4: Waist‐to‐hip ratio

2.5. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 5: Creatinine clearance [mL/min/1.73²]

2.6. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 6: Proteinuria

2.11. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 11: Fasting blood glucose

2.12. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 12: C‐reactive protein

2.17. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 17: Dietary energy intake

2.18. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 18: Quality of life: SF36 physical domain

2.19. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 19: Quality of life: SF36 mental domain

2.20. Analysis.

Comparison 2: Any weight loss intervention versus dietary intervention, Outcome 20: Quality of life: CES‐D

Comparison 3. Surgical versus non‐surgical weight loss intervention.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Mean weight loss (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3.2 Body mass index	2	17	Mean Difference (IV, Random, 95% CI)	‐10.43 [‐13.58, ‐7.29]
3.3 Waist circumference (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3.4 Body composition: fat mass (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3.5 Proteinuria (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3.6 Serum creatinine (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3.7 C‐reactive protein (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3.8 Quality of life: SF36 physical domain (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3.9 Quality of life: SF36 mental domain (change score)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

3.3. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 3: Waist circumference (change score)

3.4. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 4: Body composition: fat mass (change score)

3.5. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 5: Proteinuria (change score)

3.6. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 6: Serum creatinine (change score)

3.7. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 7: C‐reactive protein (change score)

3.8. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 8: Quality of life: SF36 physical domain (change score)

3.9. Analysis.

Comparison 3: Surgical versus non‐surgical weight loss intervention, Outcome 9: Quality of life: SF36 mental domain (change score)

Comparison 4. Weight loss intervention versus usual care or control: stage of CKD.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Mean weight loss [kg or %]	6	278	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐4.53, 1.74]
4.1.1 CKD stages 1‐5: (mean weight loss) [kg]	4	162	Mean Difference (IV, Random, 95% CI)	‐0.93 [‐8.79, 6.93]
4.1.2 Transplant: (mean weight loss) [%]	2	116	Mean Difference (IV, Random, 95% CI)	‐1.70 [‐4.42, 1.02]
4.2 Total cholesterol	5	98	Mean Difference (IV, Random, 95% CI)	‐11.92 [‐27.31, 3.47]
4.2.1 CKD stages 1‐5	4	84	Mean Difference (IV, Random, 95% CI)	‐14.02 [‐30.02, 1.99]
4.2.2 Transplant	1	14	Mean Difference (IV, Random, 95% CI)	14.10 [‐42.26, 70.46]

Comparison 5. Weight loss intervention versus usual care or control: duration of intervention.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Mean weight loss: post intervention body weight	6	248	Mean Difference (IV, Random, 95% CI)	‐1.65 [‐4.54, 1.25]
5.1.1 Intervention duration ≤ 3 months	2	109	Mean Difference (IV, Random, 95% CI)	‐2.06 [‐4.73, 0.62]
5.1.2 Intervention duration > 3 months	4	139	Mean Difference (IV, Random, 95% CI)	‐1.70 [‐5.66, 2.27]
5.2 Body mass index	4	100	Mean Difference (IV, Random, 95% CI)	‐2.49 [‐4.97, 0.00]
5.2.1 Intervention duration ≤ 3 months	1	27	Mean Difference (IV, Random, 95% CI)	0.57 [‐3.59, 4.72]
5.2.2 Intervention duration > 3 months	3	73	Mean Difference (IV, Random, 95% CI)	‐3.36 [‐5.68, ‐1.04]
5.3 Total cholesterol	5	97	Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.65, 0.18]
5.3.1 Intervention duration ≤ 3 months	1	13	Std. Mean Difference (IV, Random, 95% CI)	0.25 [‐0.85, 1.34]
5.3.2 Intervention duration > 3 months	4	84	Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.76, 0.13]
5.4 Dietary energy intake	3	64	Std. Mean Difference (IV, Random, 95% CI)	‐0.69 [‐1.88, 0.50]
5.4.1 Intervention duration ≤ 3 months	1	27	Std. Mean Difference (IV, Random, 95% CI)	0.08 [‐0.72, 0.88]
5.4.2 Intervention duration > 3 months	2	37	Std. Mean Difference (IV, Random, 95% CI)	‐1.14 [‐2.50, 0.23]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Baria 2014.

Study characteristics
Methods	Study design: prospective RCT Study dates: enrolment start and finish date not reported Study duration: 12 weeks
Participants	Country: Brazil Setting: single centre; outpatient hospital CKD clinic Inclusion criteria: BMI > 25 kg/m², aged 18 to 70 years, SBP < 180 mmHg, DBP < 100 mmHg, Hb > 11 g/dL, HbA1c < 8% Number: centre‐based exercise group (10); home‐based exercise group (8); control group (9) Mean age ± SD (years): centre‐based exercise group (52.1 ± 11.4); home‐based exercise group (50.8 ± 7.7); control group (53.4 ± 9.6) Sex (M/F): all males Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI ± SD (kg/m²): centre‐based exercise group (30.8 ± 5.1); home‐based exercise group (30.9 ± 3.9); control group (29.6 ± 1.9) Stage of CKD: 3 and 4 Mean baseline eGFR ± SD (mL/min/1.73 m²): centre‐based exercise group (25.8 ± 8.8); home‐based exercise group (29.4 ± 11.5); control group (27.7 ± 15.0) Mean baseline SBP ± SD (mmHg): not measured Mean baseline DBP ± SD (mmHg): not measured Mean BP ± SD (mmHg): centre‐based exercise group (97.7 ± 7.4); home‐based exercise group (98.8 ± 13.2); control group (98.2 ± 11.6) Mean baseline energy intake (kcal/kg/day): centre‐based exercise group (21.6 ± 6.9); home‐based exercise group (26.4 ± 7.3); control group (22.3 ± 6.1) Comorbid conditions: 20% of study population had diabetes Exclusion criteria: chronic obstructive pulmonary disease; congestive heart failure or active coronary disease; use of beta blockers or erythropoietin; positive cardiovascular stress test (positive criteria not defined)
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: aerobic exercise Home‐based exercise group Aerobic exercise program: 3 walking sessions/week on alternate days, at a location at or nearby their home. Received guided support from exercise physiologist. Sessions began at 30 minutes and increased by 10 minutes every 4 weeks during a supervised training session. Intensity was prescribed according to ventilatory threshold obtained via cardiopulmonary exercise test at baseline In‐centre based exercise group Aerobic exercise program: 3 walking sessions/week on alternate days, walking on treadmill, in‐centre supervised by an exercise physiologist. Sessions began at 30 minutes and increased by 10 minutes every 4 weeks. Intensity was prescribed according to ventilatory threshold obtained via cardiopulmonary exercise test at baseline Control group Asked to not perform any physical exercise during the study intervention period Co‐interventions None reported
Outcomes	Body weight (kg) BMI (kg/m²) Waist circumference (cm) Body composition: abdominal visceral fat (mm) and subcutaneous fat (mm), total fat mass (kg) lean body mass (kg) Inflammation: C‐reactive protein (mg/dL) Dietary intake: energy intake (kcal/kg/day)
Notes	Funding source: Foundation of Support the Research of the State of São Paulo (FAPESP no 2009/14786‐0), Support Foundation to the Federal University of São Paulo (FapUNIFESP) and Fundação Oswaldo Ramos Additional data: start and finish dates requested (see Appendix 3) Trial registration: number not reported Possible conflicts of interest for study author: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding of participants or study personnel was not described. Participants were randomised to a one of two exercise groups or control group. Therefore study participants were unlikely to be blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	A blinded assessor was used to report abdominal computed tomography. It is not reported if assessors reporting on all other outcome measures were blinded, therefore there was insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data available for 93% of study participants. Similar dropout rates in both treatment and control group
Selective reporting (reporting bias)	Unclear risk	Protocol not published; however authors appear to report on what they intended to report on as described in the study aims
Other bias	Low risk	Study appears free of other biases

DIRECT 2013.

Study characteristics
Methods	Study design: parallel RCT Recruitment: July 2005 to June 2007 Study duration: 2 years
Participants	Country: Israel Setting: single centre; workplace at a research centre with an on‐site medical clinic Inclusion criteria: adults aged 45 to 65 years with BMI ≥ 27 kg/m² or type 2 diabetes or coronary heart disease Number: 99/318 of study participants met inclusion criteria Low fat diet group (34); Mediterranean diet group (36); low carbohydrate diet group (29) Mean age ± SD (years): not available for subgroups Sex (M/F): not available for subgroups Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI ± SD (kg/m²): low fat diet group (30.6 ± 3.2); Mediterranean diet group (31.2 ± 4.1); low carbohydrate diet group (30.8 ± 3.5) Stage of CKD: subgroup participants with an eGFR 30 to 60 mL/min/1.73 m²were included in this review Mean baseline eGFR ± SD (mL/min/1.73 m²): not available for subgroups Mean baseline energy intake ± SD (kcal/day): not available for sub‐groups Mean baseline SBP ± SD (mmHg): low fat diet group (130.2 ± 12.7); Mediterranean diet group (131.4 ± 14.7); low carbohydrate diet group (133.4 ± 15.0) Mean baseline DBP ± SD (mmHg): low fat diet group (76.8 ± 9.8); Mediterranean diet group (80.2 ± 8.2); low carbohydrate diet group (80.2 ± 6.9) Mean baseline energy intake (kcal/kg/day): not reported Comorbid conditions: type 2 diabetes; coronary heart disease; hypertension Exclusion criteria: pregnant or lactating women; a SCr > 176 µmol/L (2 mg/dL); liver dysfunction (twofold or higher of the upper limit of normal in ALT or AST); intestinal problems that would prevent adherence to any of the diets; active cancer
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary Intervention group 1 (low fat, restricted energy) Based on American Heart Association guidelines. Daily energy intake of 1500 kcal for women and 1800 kcal for men, 30% from fat, 10% from saturated fat and an intake of 200 mg of cholesterol per day. Participants were educated at group sessions to consume low fat grains, vegetable, fruits, and legumes and limit their intake of additional fats, sweets, and high fat snacks. Dietitians led groups of 17 to 19 patients for dietary sessions. Group education sessions were held at week 1, 3, 5, 7 and thereafter every 6 weeks for a total of 18 group sessions A further 6 individual phone calls 10 to 15 minutes were made by a different dietitian to assist struggling individuals with motivation. A group of spouses also received education to strengthen their support to participants Intervention group 2: (Mediterranean restricted energy) Moderate fat, Mediterranean restricted energy daily to 1500 kcal for women and 1800 kcal for men, goal no more than 35% of energy from fat, main sources of fat were 30 g to 45g of olive oil and a handful of nuts per day Dietitians led groups of 17 to 19 patients for dietary sessions. Week 1, 3, 5, 7 and thereafter every 6 weeks a total of 18 group sessions ‐ were educated to eat diet rich in vegetables, low in red meat, fish, and poultry to replace beef and lamb A further 6 individual phone calls 10 to 15 minutes were made by a different dietitian to assist struggling individuals with motivation. A group of spouses also received education to strengthen their support to participants Intervention group 3 (low carbohydrate, non‐restricted energy) Advised to consume 20 g of carbohydrate per day for the 2‐month induction phase gradual increase to a max of 120 g/day ‐ the intake of total energy, protein, and fat were not limited. The patients were counselled to choose vegetarian sources of fat and protein, and to avoid trans‐fat. Diet was based on the Atkins diet Dietitians led groups of 17 to 19 patients for dietary sessions. Week 1, 3, 5, 7 and thereafter every 6 weeks a total of 18 group sessions A further 6 individual phone calls 10 to 15 minutes were made by a different dietitian to assist struggling individuals with motivation. A group of spouses also received education to strengthen their support to participants Co‐interventions None reported
Outcomes	Body weight (kg) BMI (kg/m²) Waist circumference (cm) Albuminuria (mg/L) (data not available for subgroup) SBP (mmHg) DBP (mmHg) Anti‐hypertensive medication changes (data not available for subgroup) Hypoglycaemic medication changes (data not available for subgroup) Fasting blood glucose (mmol/L) Total cholesterol (mmol/L) LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Triglycerides (mmol/L) Lipid lowering medication changes (data not available for sub‐study) Inflammation: C‐reactive protein (data not available for sub‐study) Adherence to treatment (data not available for sub‐study)
Notes	Founding source: Israeli Ministry of Health, Chief Scientist Office (Project No. 300000‐4850) and The Dr. Robert C. and Veronica Atkins Research Foundation Trial registration: ClinicalTrials.gov No. NCT00160108 Additional data: requested ‐ See Appendix 3 Possible conflicts of interest for study author: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised by strata of sex, age, BMI, history of coronary heart disease, type 2 diabetes, and current use of statins
Allocation concealment (selection bias)	Unclear risk	Insufficient information about the sequence generation process to permit judgment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Masking of patients or study personnel not reported in the study report. Participants were randomised to either one of three different dietary groups. Therefore, participants and investigators (dietitians) were unlikely to be blinded to treatment allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The clinic and laboratory staff members were unaware of the treatment assignments and the study coordinators were unaware of all outcome data until the end of the intervention"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low and balanced attrition rates across each groups with similar reasons for withdrawal
Selective reporting (reporting bias)	Low risk	Authors appear to report on what they intended to report on as described in the study aims
Other bias	High risk	Post hoc reporting of sub‐groups with CKD stages 3 to 4

Ikizler 2018.

Study characteristics
Methods	Study design: prospective RCT (2 x 2 factorial design) Recruitment: October 2010 to February 2014. Study duration: 4 months
Participants	Country: USA Setting: multicentre (medical centre (2), medical research centre (1), University (1)) Inclusion criteria: CKD stages 3 and 4 (eGFR 15 to 60 mL/min/1.73 m²); aged 18 to 75 years; BMI ≥ 25 kg/m²; life expectancy ≥ 1 year; ability to understand and provide informed consent Number: aerobic exercise + energy restriction group (24); usual activity + energy restriction group (28); aerobic exercise + usual diet group (27); usual activity + usual diet group (26) Median age, IQR (years): aerobic exercise + energy restriction group (53.5, 49.2 to 59.8); usual activity + energy restriction group (58.5, 45.8 to 62.0); aerobic exercise + usual diet group (58.0, 48.5 to 62.0), usual activity + usual diet group (58.55,45.8 to 64.0) Sex (M/F): aerobic exercise + energy restriction group (17/13); usual activity + energy restriction group (15/13); aerobic exercise + usual diet group (15/12); usual activity + usual diet group (17/9) Baseline characteristics Nationality: not reported Ethnicity (white/black/other): aerobic exercise + energy restriction (22/7/1); usual activity + energy restriction (19/9/0); aerobic exercise + usual diet (17/1/3); usual activity + usual diet (16/8/2) Median baseline BMI, IQR (kg/m²): aerobic exercise + energy restriction group (32.8, 30.4 to 35.8); usual activity + energy restriction group (32.8, 28.7 to 37.1); aerobic exercise + usual diet group (31.0,28.0 to 36.2); usual activity + usual diet group (35.5, 30.6 to 41.5) Stage of CKD: CKD stages 3 to 4 Median baseline eGFR, IQR (mL/min/1.73 m²): aerobic exercise + energy restriction group (41.8, 27.1 to 483); usual activity + energy restriction group (44.6, 31.9 to 52.9); aerobic exercise + usual diet group (44.0, 30.2 to 51.2); usual activity + usual diet group (39.1, 31.1 to 49.8) Median baseline SBP, IQR (mmHg): aerobic exercise + energy restriction group (128, 109 to 141); usual activity + energy restriction group (132, 118 to 141); aerobic exercise + usual diet group (134, 114 to 144); usual activity + usual diet group (136, 118 to 142) Median baseline DBP, IQR (mmHg): aerobic exercise + energy restriction group (75.0, 68.0 to 84.2); usual activity + energy restriction group (78.0, 71.5 to 86.5); aerobic exercise + usual diet group (78.0, 73.5 to 84.0); usual activity + usual diet group (76.5, 72.0 to 83.0) Mean baseline energy intake, IQR (kcal/day): not reported Comorbid conditions: type 2 diabetes (25%); hypertensive (91%) Exclusion criteria: any acute inflammatory condition (including chronic infection requiring treatment and collagen vascular disease, including active gout); pregnancy; taking high‐dose antioxidants (vitamin E or C); chronic use of anti‐inflammatory medication, except low‐dose (< 10 mg/day) prednisone and aspirin (< 100 mg/day); significant cardiac or vascular disease (symptomatic disease or CVD event, including congestive heart failure, within 6 months); significant occlusive atherosclerotic disease or Ischaemic disease (on non‐invasive or invasive diagnostic procedures); significant physical immobility or disabilities (joint replacement or muscular disorders); type 1 diabetes mellitus or type 2 diabetes mellitus requiring insulin therapy; history of poor adherence to medical regimen
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary + physical activity Aerobic exercise + energy restriction group Supervised aerobic exercise physical activity for a maximum of 30 to 45 minutes, 3 times/week and 10% to 15% reduction in total daily energy intake (300 kcal to 500 kcal reduction) from the usual daily energy consumption for 4 months duration. The exercise sessions were delivered by an exercise specialist and clinical exercise physiologists. The goal was for a training intensity of approximately 60% to 80% VO²Max. It is not reported who delivered the dietary intervention nor what educational materials and counselling were provided. Usual activity + energy restriction group 10% to 15% reduction in total daily energy intake (300 kcal to 500 kcal reduction) from the usual daily energy consumption for 4 months duration. It is not reported who delivered the dietary intervention nor what educational materials and counselling were provided Aerobic exercise + usual diet group Supervised aerobic exercise physical activity for a maximum of 30 to 45 minutes, 3 times/week for 4 months duration. The exercise sessions were delivered by an exercise specialist and clinical exercise physiologists. The goal was for a training intensity of approximately 60 to 80% VO²Max Usual activity + usual diet group Advised to continue with usual diet and usual activity Co‐interventions All study participants received information as part of a CKD diet. They were advised to include large amounts of fresh unprocessed plant foods with moderate levels of lean protein and fats and avoid high energy rich meals in processed, easily digestible, quickly absorbable foods and drinks
Outcomes	Body weight (kg) Weight loss (kg) BMI (kg/m²) Waist‐to‐hip ratio Body composition (% body fat) SBP (mmHg) DBP (mmHg) HbA1c (%) Fasting blood glucose (mg/dL) Adverse events Adherence to treatment
Notes	Founding source: National Institutes of Health grants R01HL070938 from National Heart, Lung, and Blood Institute; K24DK62849, P30DK020593, and P30DK035816 from National Institute of Diabetes and Digestive and Kidney Diseases; P30ES000267 from the National Institute of Environmental Health Sciences; and Clinical Translational Science Awards UL1‐TR000445 and UL1TR000423 from the National Center for Advancing Translational Sciences Trial registration: ClinicalTrials.gov No. NCT01150851 Possible conflicts of interest for study author: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Participants were assigned to one of the study arms using a permuted block randomisation strategy 1:1 ratio"
Allocation concealment (selection bias)	Unclear risk	Insufficient information about the sequence generation process to permit judgment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Because of the nature of the intervention, the study was unblinded"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information about the blinding of outcome assessments to permit judgment
Incomplete outcome data (attrition bias) All outcomes	Low risk	11.5% attrition rate with balanced dropouts across each groups with similar reasons across groups for withdrawal
Selective reporting (reporting bias)	Unclear risk	No study protocol paper published. Authors appear to report on what they intended to report on as described in the study aims
Other bias	Low risk	The study appears to be free of other sources of bias

Jesudason 2013.

Study characteristics
Methods	Study design: parallel RCT (75 eligible, 65 randomised, 45 analysed) Study dates: enrolment start and finish date not reported Study duration: 12 month intervention
Participants	Country: Australia Setting: single centre; research organisation Inclusion criteria: type 2 diabetes mellitus (drug treated or fasting blood glucose > 7mmol/L or 2 hour blood glucose > 11.1 mmol/L) with microalbuminuria (30 to 300 mg/24 hour or ACR of 3.0 mg/mmol to 30 mg/mmol); eGFR > 40 mL/min/1.73 m² and BMI > 27 kg/m² Number: moderate protein group (21); standard protein group (24) Mean age ± SD (years): moderate protein group (59.4 ± 2.2); standard protein group (62.4 ± 1.7) Sex (M/F): moderate protein group (15/6); standard protein group (20/4) Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): moderate protein group (36.7); standard protein group (35.4) Stage of CKD: 1 and 2 and part of stage 3 (eGFR > 40 mL/min/1.73 m²) Mean baseline eGFR ± SD (mL/min/1.73 m²): moderate protein group (98 ± 6); standard protein group (91 ± 6) Mean baseline SBP ± SD (mmHg): measured but not reported. Mean baseline DBP ± SD (mmHg): moderate protein group (75 ± 7); standard protein group (71 ± 9) Mean baseline energy intake (kJ/day): moderate protein group (9300 ± 5300); standard protein group (8400 ± 3768) Comorbid conditions: type 2 diabetes (100%) Exclusion criteria: coronary artery disease or any other active disease of clinical significance
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary Moderate protein group 6000 kJ/day for women, 7000 kJ/day for men. Target 30% protein, 30% fat, 40% carbohydrate. Protein target 90 to 120 g/day. Alcohol was limited to 2 standard drinks/week. Participants attended a diet visit every 2 weeks for 16 weeks and monthly visits for measurement of weight, BP, and diet. A booklet with dietary information, recipes and a sample meal plan was provided. It was not reported who delivered the dietary intervention Standard protein group 6000 kJ/day for women, 7000 kJ/day for men. Target 20% protein, 30% fat, 50% carbohydrate. Protein target 55 to 70 g/day. Alcohol was limited to 2 standard drinks/week. Participants attend a diet visit every 2 weeks for 16 weeks and monthly visits for measurement of weight, BP, and diet. A booklet with dietary information, recipes and a sample meal plan was provided. It was not reported who delivered the dietary intervention Co‐interventions Not reported
Outcomes	Body weight (kg) Body composition (lean mass & fat mass ‐ DEXA) Albuminuria (24‐h urinary albumin excretion) (mg/min) Glomerular hyperfiltration (defined as GFT > 120 mL/min) Measured GFR (mL/min/1.73 m²) SBP (mmHg) DBP (mmHg) Anti‐hypertensive medication changes HbA1c (%) Hypoglycaemic medication changes Adherence to treatment Dietary intake (energy intake kJ/day)
Notes	Founding source: not reported Additional data: requested ‐ Appendix 3 Trial registration: The Australian New Zealand Clinical Trials Registry (ANZCTR) No. 12608000045314 Possible conflicts of interest for study author: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Random assignment was carried out before inclusion on the basis of computer‐generated random‐number list"
Allocation concealment (selection bias)	Low risk	Quote: "The allocation sequence was concealed in sealed envelopes from the researcher who enrolled and assessed participants"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding of participants or study personnel was not described. Participants were randomised to one of two dietary intervention therefore study participants were unlikely to be blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	High risk	High levels of attrition in both groups: moderate protein group (38%); standard protein group (23%)
Selective reporting (reporting bias)	High risk	Selective reporting of some outcome measures after baseline
Other bias	Unclear risk	Insufficient information to permit judgement. Some imbalances at baseline in albuminuria. Also wide ranging baseline kidney function

Kittiskulnam 2014.

Study characteristics
Methods	Study design: prospective RCT (299 patients assessed for eligibility; 26 randomised) Recruitment: enrolment July 2012 to February 2013 Study duration: 6 months
Participants	Country: Thailand Setting: single centre, outpatient hospital clinic Inclusion criteria: aged 18 to 65 years; biopsy‐proven IgAN with persistent proteinuria > 1 g/day (despite maximal tolerated doses of ACEIs or ARBs) on at least 3 consecutive determinations in the 6‐month period before the study; overweight or obese (defined by BMI > 23 kg/m² obesity criteria in Asia Pacific); BP control below 125/75 mmHg. For the patients who were receiving steroid and/or immunosuppressive agents, the dose adjustment was prohibited for the previous 6 months before enrolment Number: low energy diet group (13); usual dietary intake group (13) Mean age ± SD (years): low energy diet group (45.5 ± 11.9); usual dietary intake group (45.4 ± 16.2) Sex (M/F): low energy diet group (6/7); usual dietary intake group (6/7) Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI ± SD (kg/m²): low energy diet group (28.5 ± 4.8); usual dietary intake group (28.7 ± 4.8) Stage of CKD: stages 1 to 4 Mean baseline eGFR ± SD (mL/min/1.73 m²): low energy diet group (60.1 ± 25.5); usual dietary intake group (56.6 ± 29.6) Mean baseline SBP ± SD (mmHg): low energy diet group (125.1 ± 8.5); usual dietary intake group (124.8 ± 14.7) Mean baseline DBP ± SD (mmHg): low energy diet group (75.1 ± 5.3); usual dietary intake group (74.9 ± 10.0) Mean baseline energy intake (kJ/day): not reported Comorbid conditions: type 2 diabetes (15%); metabolic syndrome (50%) Exclusion criteria: rapid loss of GFR > 30% in 6 months; nephrotic‐range proteinuria requiring immunosuppressive treatments; presence of crescent formation more than 10% in kidney biopsy; GFR < 15 mL/min/1.73 m²; BMI > 40 kg/m²; diabetic kidney disease; pregnancy or lactation; malignancy‐state patients with clinical malnutrition
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary Intervention group (low‐energy diet group) Participants were instructed to reduced energy intake by 500 kcal/day and prescribed low‐protein diet (0.6 to 0.8 g/kg/day), and restriction of sodium intake to < 2 g/day with macronutrient content of 25% to 30% fat and 55% to 60% carbohydrates for a 6‐month period Participants also received standard treatments of care including maximal dosage of ACEi or ARB and other antihypertensive agents to achieve a BP < 125/75 mmHg. Participants were also advised about diet that retards CKD progression. Participants received once a month clinic visits and phone calls in‐between. The intervention was delivered by a clinician and nutritionist Control group (usual dietary intake group) Participants received standard treatments of care including maximal dosage of ACEi or ARB and other antihypertensive agents to achieve a BP < 125/75 mmHg and prescribed low‐protein diet (0.6 g/kg to 0.8 g/kg/day), and restriction of sodium intake to < 2 g/day. Participants were also advised about diet that retards CKD progression. Participants received once a month clinic visits and phone calls in‐between. The intervention was delivered by a clinician and nutritionist Co‐interventions Participants in both groups were also informed to stop smoking and avoid NSAIDs Participants in both groups were encouraged to engage in moderate‐intensity aerobic exercises at least 3 to 5 days/week that lasted 30 minutes for each session
Outcomes	Body weight (kg) Weight loss (kg) BMI (kg/m²) Waist circumference (cm) Body composition (% body fat, % muscle) SCr (mg/dL) Proteinuria (g/day) SBP (mmHg) DBP (mmHg) Fasting blood glucose (mg/dL) Total cholesterol (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Triglycerides (mg/dL) Dietary intake energy intake (kcal/day)
Notes	Founding source: Ratchadapiseksompotch Fund, Chula‐longkorn University Additional data: not requested Trial registration: Clinical trial registration (clinicaltrial.gov NCT01773382) Possible conflicts of interest for study author: not declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patients were randomised by block randomisation using varying blocks into two groups"
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	Neither participants nor personnel were blinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "The clinician and nutritionist who gave dietary advice were not blinded". These same clinicians were responsible for measuring and recording a number of outcome data including body weight
Incomplete outcome data (attrition bias) All outcomes	Low risk	No study dropouts and no missing data
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement. Not study protocol published. Dietary compliance information collected but not reported
Other bias	Unclear risk	Study appears free of other biases. Quote: "The study statistician was blinded throughout the study"

LANDMARK 3 2013.

Study characteristics
Methods	Study design: prospective RCT Study dates: February 2008 to March 2010 Study duration: 12 months
Participants	Country: Australia Setting: single centre; hospital outpatient clinic Inclusion criteria: 18 to 75 years; moderate CKD (eGFR 25 to 60 mL/min/1.73 m²); had one or more uncontrolled cardiovascular risk factors such as BP exceeding target; overweight (BMI > 25 kg/m²); poor diabetic control (HbA1c > 7%), or lipids exceeding target Number: lifestyle intervention group (36); control group (36) Mean age ± SD (years): lifestyle intervention group (60.2 ± 9.7); control group (62.0 ± 8.4) Sex (M/F): lifestyle intervention group (24/12), control group (21/15) Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI ± SD (kg/m²): lifestyle intervention group (32.5 ± 6.8); control group (33.0 ± 8.0) Stage of CKD: stages 3 and 4 Mean baseline eGFR ± SD (mL/min/1.73 m²): lifestyle intervention group (38.4 ± 8.8); control group (39.4 ± 8.9) Mean baseline peripheral SBP ± SD (mmHg): lifestyle intervention group (128.8 ± 16.1); control group (132.3 ± 12.0) Mean baseline peripheral DBP ± SD (mmHg): lifestyle intervention group (74.9 ± 8.1); control group (71.1 ± 9.0) Mean baseline energy intake (kcal/kg/day): not reported Comorbid conditions: type 2 diabetes; coronary heart disease; hypertension Exclusion criteria: intervention for or symptomatic coronary artery disease (within 3 months); current heart failure (NYHA class III and IV) or significant valvular heart disease; pregnant or planning to become pregnant; life expectancy or anticipated time to dialysis or transplant < 6 months
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: physical activity + dietary + behaviour change Lifestyle intervention group In addition to standard care, participants received cardiovascular risk management provided by a multidisciplinary clinic (including a CKD nurse practitioner, dietitian, exercise physiologist, diabetic educator, psychologist, and social worker), exercise training and a lifestyle intervention Exercise training involved 150 minutes of moderate intensity exercise/week, with 8 weeks of 2 to 3 gym sessions/week supervised by an accredited clinical exercise physiologist The lifestyle intervention involved 4 weeks of group behaviour and lifestyle modification facilitated by a dietitian and psychologist. The program focused on sustainable diet and behaviour change to assist with weight loss Standard care (control group) Received usual standard clinic care, which included review by a nephrologist, recommended lifestyle modification but no specific information or education, and referral to an allied health professional on an ad hoc basis Co‐interventions None reported
Outcomes	Weight loss (kg) BMI (kg/m²) SCr (µmol/L) Fasting glucose (mmol/L) Triglycerides (mmol/L) Total cholesterol (mmol/L) HDL cholesterol (mmol/L LDL cholesterol (mmol/L) HbA1c (%): diabetics only Adherence to treatment
Notes	Founding source: National Health and Medical Research Council–funded Centre for Clinical Research Excellence–Vascular and Metabolic Health of the University of Queensland, and Department of Nephrology at Princess Alexandra Hospital Trial registration: The Australian New Zealand Clinical Trials Registry (ANZCTR) No. 12608000337370 Additional data: Appendix 3 Possible conflicts of interest for study author: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote "Patients were assigned to either the lifestyle intervention group or to the usual care control group in a 1:1 ratio using a computer random assignment program."
Allocation concealment (selection bias)	Unclear risk	Insufficient information provided to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	The study was an open label study ‐ participants and personnel were not blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information provided to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Low risk	< 15% attrition rates across each groups with similar reasons for withdrawal
Selective reporting (reporting bias)	Low risk	Authors appear to report on what they intended to report on as described in the study aims
Other bias	Unclear risk	The study appears to be free of other sources of bias

Leehey 2009.

Study characteristics
Methods	Study design: parallel RCT Recruitment: enrolment start and finish date not reported Study duration: 24 weeks
Participants	Country: USA Setting: Single centre, renal outpatient hospital clinic Inclusion criteria: CKD stages 2 to 4; type 2 diabetes mellitus; BMI ≥ 30 kg/m²; proteinuria (urine PCR > 200 mg/g for ≥ 3 months); treatment with ACEi or ARB, aspirin, and statin (if low density lipoprotein > 100 mg/dL) Number: Intervention group (7); control group (4) Mean age (range): 66 years (55 to 81). Sex (M/F): all males Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): not reported Stage of CKD: stages 2 to 4 Mean baseline eGFR ± SD (mL/min/1.73 m²): not reported Mean baseline SBP ± SD (mmHg): intervention group (130 ± 28); control group (157 ± 14) Mean baseline DBP ± SD (mmHg): intervention group (71 ± 20); control group (83 ± 20) Mean baseline energy intake ± SD (kcal/day): intervention group (1878 ± 563); control group (1869 ± 13) Comorbid conditions: type 2 diabetes mellitus (100%) Exclusion criteria: hyperparathyroidism/osteoporosis; symptomatic neuropathy/retinopathy; positive stress test due to coronary arterial disease; symptomatic CVD; congestive heart failure (NYHA Class III or IV); chronic obstructive pulmonary disease (FEVI < 50% predicted and/or requires supplemental oxygen support during exercise); complaints of angina during the stress test; cerebrovascular disease/cognitive impairment; kidney transplant; inability to walk on the treadmill; any unforeseen illness or disability that would preclude exercise testing or training; participation in a formal exercise program within the previous 12 weeks
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: aerobic exercise Intervention group Participants underwent thrice weekly exercise sessions for 6 weeks in a hospital research laboratory, followed by 18 weeks of home exercise sessions. Participants received instruction in walking and proper shoe selection. An introductory session was completed to educate participants on developing a walking program and to familiarize walking on a treadmill. Exercise programs were individualised and based on results of a baseline exercise test. Sessions included light warm up and stretching and began at 30 minutes and gradually increased by five minutes every two weeks. After 6 weeks of supervised walking program participants continued their program unsupervised in their home or local community and asked to increase their walk by 10% each week Control group Participants received standard medical care which included medical treatment for diabetes and chronic liver disease, including diabetes education. The control group and completed the same battery of testing but did not participate in any exercise training Co‐interventions Intensive medical management, diabetes teaching, and monitoring of food intake
Outcomes	Body weight (kg) Body composition: lean mass (%) and fat mass (%) CrCl (units) SCr (mg/dL) Proteinuria (mg/24 hours) SBP (mmHg) DBP (mmHg) HbA1c (%) Total cholesterol (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Triglycerides (mg/dL) Inflammation: C‐reactive protein (mg/dL) Dietary intake: energy intake (kcal/day) Physical activity behaviours (exercise duration minutes)
Notes	Founding source: not reported Additional data: requested see Appendix 3 Trial registration: not reported Possible conflicts of interest for study author: nil declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation used to allocate to treatment or control group
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding of participants or study personnel was not described. Participants were randomised to one of two intervention groups therefore study participants were unlikely to be blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Selective reporting (reporting bias)	Low risk	Authors report on what they intended to report on as described in the study aims
Other bias	Unclear risk	Insufficient information to permit judgement, no indication of adherence to intervention or whether the control group changed their exercise habits during the study

Leehey 2016.

Study characteristics
Methods	Study design: parallel RCT (48 patients assessed for eligibility; 36 randomised) Recruitment: enrolment start and finish date not reported Study duration: intervention 52 weeks (follow‐up 52 weeks)
Participants	Country: USA Setting: single centre, hospital outpatient clinic Inclusion criteria: type 2 diabetes mellitus, obesity (BMI > 30 kg/m²) and CKD stages 2 to 4 with proteinuria (urine PCR > 200 mg/g) for at least 3 months Number: intervention group (14); control group (18) Mean age ± SD (years): intervention group (65.4 ± 8.7); control group (66.6 ± 7.5) Sex (M/F): all males. Baseline characteristics Nationality: American Ethnicity: Caucasian (19); African American (13); Hispanic origin (4) Mean baseline BMI (kg/m²): intervention group (36.2 ± 4.8); control group (37.4 ± 4.2) Stage of CKD: stages 2 to 4 Mean baseline eGFR ± SD (mL/min/1.73 m²): intervention group (40.9 ± 18.1); control group (38.9 ± 20.3) Mean baseline SBP ± SD (mmHg): not measured Mean baseline DBP ± SD (mmHg): not measured Mean baseline energy intake ± SD (kcal/day): not reported Comorbid conditions: type 2 diabetes mellitus (100%) Exclusion criteria: CVD precluding participation in exercise program; moderate to severe congestive heart failure (NYHA class II‐IV); moderate to severe chronic obstructive pulmonary disease; history of cerebrovascular accident with cognitive impairment; kidney transplant; inability to walk on a treadmill
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: exercise (aerobic and resistance) + dietary Intervention group (exercise + diet) A kidney dietitian devised a diet with a 200 to 250 kcal deficit from the individuals estimated energy needs. Participants received a nutritional counselling session at baseline with 9 follow‐up phone calls during the study. Individualised nutritional counselling with 200 to 250 kcal energy deficit plus 3 times/week supervised exercise 60 min cardiovascular and 30 min resistance training 12 weeks, then 40 weeks home exercise 3 x 60 min or 6 x 30min sessions. Participants received nutritionally counselling and underwent a supervised exercise program. Exercise program consisted of a 12 week (3 days/week) supervised program of ~60 minute aerobic session (interval training on treadmill, elliptical trainer, and cycle ergometer) and ~ 20 minutes to 30 minutes of resistance training (lower body exercises using elastic bands, hand‐held weights, or weight machine) followed by 40 weeks of home exercise. Home exercise consisted of exercise as 60 minutes thrice weekly or 30 minutes 6 times/week. Participants received weekly phone calls and were encouraged to meet with their trainer on a monthly basis Control group (diet alone) A kidney dietitian devised a diet with a 200 to 250 kcal deficit from the individuals estimated energy needs. Participants received a nutritional counselling session at baseline with 9 follow‐up phone calls during the study. Participants underwent medical care by their usual physicians, with medications adjusted according to standards of medical practice at the medical centre Co‐interventions Referral to MOVE program, a lifestyle modification program, ACEi or ARB, aspirin therapy and statin therapy unless contraindicated
Outcomes	BMI (kg/m²) Body composition: body fat (%), lean weight (kg), fat weight (kg) Proteinuria (mg/g) Albuminuria (mg/g) SBP (mmHg) HbA1c (%) Total cholesterol (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Triglycerides (mg/dL) Inflammation: C‐reactive protein (mg/dL) Adherence to treatment Health‐related quality of life (SF‐36 Health Survey and CES‐D) Adverse patient outcomes associated with each weight loss intervention
Notes	Founding source: Department of Veterans Affairs, USA Additional data: requested see Appendix 3 Trial registration: ClinicalTrials.gov (NCT01036490) Possible conflicts of interest for study author: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomised using a computer generated permuted block scheme"
Allocation concealment (selection bias)	Low risk	Insufficient information to permit judgement ‐ not reported if allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants not blinded, personnel undertaking intervention not blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Study personnel supervising testing were blinded to group assignment."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	Unclear risk	Study appears free of other biases. Study underpowered ‐ didn't reach target sample size to detect treatment effect looking for

MacLaughlin 2014.

Study characteristics
Methods	Study design: parallel RCT Study dates: March 2010 to June 2011 Study duration: 12 month follow‐up
Participants	Country: UK Setting: multicentre (3 sites), tertiary hospital outpatient nephrology clinics Inclusion criteria: male or female > 18 years; BMI 35to 45 kg/m²; eGFR of 20 to 60 mL/min/1.73 m²; previously attempted weight loss; written informed consent Number: intervention group (5); control group (6) Median age; 25th, 75th percentile (years): intervention group (51; 47.5, 55); control group (53; 46.5, 66) Sex (M/F): intervention group (0/5); control group (4/6) Baseline characteristics Nationality: not reported Ethnicity (white/black): intervention group (3/2); control group (3/3) Median baseline BMI; 25th, 75th percentile (kg/m²): intervention group (40.3; 37.3, 43.5); control group (37.4; 35.8, 40.0) Stage of CKD: stages 3 and 4 Median baseline eGFR; 25th, 75th percentile (mL/min/1.73 m²): intervention group ( 37; 22, 53); control group (28; 23, 32) Median SBP; 25th, 75th percentile (mmHg): intervention group (118; 116, 142): control group (135; 117, 144) Median DBP; 25th, 75th percentile (mmHg): intervention group (80; 72, 88); control group (135; 65, 92) Mean baseline energy intake (kcal/kg/day): not reported Comorbid conditions: intervention group (diabetes (1/5); metabolic syndrome (5/5)); control group (diabetes (4/6); metabolic syndrome 6/6) Exclusion criteria: pregnancy; chronic liver disease; previous bariatric surgery; gastric surgery or large hiatus hernia; psychiatric illness including anxiety; mood and untreated eating disorders; malnutrition; infection or course of antibiotics within the last month; unfit for anaesthesia or surgery; unwilling to consider surgical treatment; previous kidney transplant
Interventions	Intervention type classification: mixed ‐ bariatric surgery + pharmacological + lifestyle Weight loss intervention/s used: bariatric surgery (sleeve gastrectomy) + lifestyle management Intervention group: laparoscopic sleeve gastrectomy + dietary + physical activity support Laparoscopic sleeve gastrectomy surgery with a final volume of 100 to 200 mL. Participants were provided with dietary education including renal‐specific written information. Dietary intake, following progression through liquid to semi‐solid foods, was reviewed by telephone at 1, 4, and 6 weeks post surgery and also at study visits at 3, 6, 9, and 12 months post surgery. Dietary energy intake was restricted to approximately 1000 kcal/day post surgery, low‐fat choices were encouraged, and a daily multivitamin and mineral supplement was prescribed Surgery was performed by an experienced minimal access surgeon (AGP). It was not reported who delivered the dietary advice Comparator group: behavioural: weight management program Received best medical care: individualised dietary and physical activity prescription + orlistat. Patients attended monthly appointments during the six month intervention period, and for monitoring and support at 9 and 12 months. It was not reported who delivered the dietary advice Co‐interventions Nil
Outcomes	Body weight (kg) BMI (kg/m²) Weight loss (%) Waist circumference (cm) Body composition (fat mass and lean body mass) SCr (mg/dL) Proteinuria (urinary PCR) (mg/mmol) SBP (mmHg) DBP (mmHg) Inflammation: high sensitivity C‐reactive protein (mg/L) Adherence to treatment HRQoL: SF‐36 physical domain/mental domain scores Hypoglycaemic medication changes Hospitalisation Adverse patient outcomes associated with each weight loss intervention
Notes	Founding source: Doctoral fellowship awarded to Dr Helen MacLaughlin by King's College Hospital NHS Foundation Trust Additional data: requested and received see Appendix 3 Trial registration: ClinicalTrials.gov (NCT01053130) Possible conflicts of interest for study author: nil declared Two‐thirds of the patients in the control group were unable to obtain orlistat for 3 to 6 months of the study period due to an international problem with production of the drug
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer‐generated random allocation sequence, with blocked permutations of 2‐4"
Allocation concealment (selection bias)	Low risk	Participant allocation was generated and held by an independent professional external to the study sites
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding of participants or study personnel was not described. Participants were randomised to bariatric surgery or usual medical care. Therefore study participants were unblinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported if outcome assessors were blinded. Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	High risk	High 30% dropout rate
Selective reporting (reporting bias)	High risk	Compliance with diet and physical activity and medication change were prespecified but not reported on
Other bias	High risk	Blocked randomisation in an unblinded RCT Very low recruitment update 10%

Morales 2003a.

Study characteristics
Methods	Study design: parallel RCT (98 patients assessed for eligibility; 22 randomised; randomly assigned 2:1 ratio) Recruitment: enrolment start and finish date not reported Study duration: 5 months (2 month observational period, 3 month intervention)
Participants	Country: Spain Setting: single‐centre; hospital outpatient clinic Inclusion criteria: a chronic (disease duration > 1 year before the study) proteinuric (proteinuria with > 1 g/24 hour of protein on at least 3 consecutive determinations in the 6‐month period before the study); nephropathy of diabetic or non‐diabetic cause; presence of overweight or obesity (BMI > 27 kg/m²); SCr < 2 mg/dL Number: intervention group (20); control group (10) Mean age ± SD (years): intervention group (56.5 ± 15.2); control group (56.1 ± 10.1) Sex (M/F): intervention group (11/9), control group (7/3) Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): intervention group (33.0 ± 3.5); control group (34.3 ± 5.7) Stage of CKD: stages 1 to 4 Mean baseline eGFR ± SD (mL/min/1.73 m²): not reported Mean baseline SBP ± SD (mmHg): intervention group (140 ± 24.1); control group (135 ± 12.4) Mean baseline DBP ± SD (mmHg): intervention group (79.6 ± 8.3 control group (83 ± 9.7) Mean baseline energy intake ± SD (kcal/day): not reported Comorbid conditions: type 2 diabetes mellitus (47%) Exclusion criteria: patients with an unstable clinical condition; rapid loss of kidney function; nephrotic syndrome requiring diuretic therapy; immunosuppressive treatments; hypertension requiring more than 2 anti‐hypertensive drugs for its control
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary Intervention group (diet group) Prescribed an energy restricted diet of 500 kcal reduction with respect to their usual diet with a target of 25% to 30% fat, 55% to 60% carbohydrate Protein content was adjusted to 1 to 1.2 g/kg/day. Intakes monitored with 3 day food diaries at baseline and 3 months All patients were attended by the same physicians of the clinical nutrition unit. Nil further information on intervention delivery information. Control group Prescribed a protein intake of 1 to 1.2 g/kg/day, monitored with 3 day food diaries at baseline and 3 months Co‐interventions ACEi, ARB, and non‐dihydropyridine calcium channel blockers were withdrawn in patients treated with these drugs at least 6 weeks before randomisation because of their known antiproteinuric effect. Patients also were instructed to avoid NSAIDs during the study. Patients administered statins for hyperlipidaemia or antihypertensives other than ACEi, ARB, or non‐dihydropyridine calcium channel blockers (including diuretics and ’‐blockers) were instructed to continue these treatments during the study, but with no change in dose
Outcomes	Body weight (kg) Weight loss (%) BMI (kg/m²) CrCl (mL/min/1.73 m²) SCr (mg/dL) Proteinuria (g/24 hour) SBP (mmHg) DBP (mmHg) Total cholesterol (mmHg) LDL cholesterol (mmHg) HDL cholesterol (mmHg) Triglycerides (mmHg)
Notes	Founding source: not reported Trial registration: Not applicable as published before 2006 Possible conflicts of interest for study author: Not declared (no statement provided)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	Same physicians saw all patients and assessed food diaries ‐ which indicated they were not blinded to the intervention group allocation
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcomes assessed by physicians involved in the intervention delivery
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement. Attrition rate and reasons for drop‐out were not reported
Selective reporting (reporting bias)	Unclear risk	Some lab evaluations measures listed in the methods were not reported in the results, Intervention adherence not reported
Other bias	Low risk	Funding source and any possible conflicts of interest not reported. No baseline imbalance evident. Stopping antiproteinuric drugs no longer likely able to be done in a study such as this due to their established protective effects

Orazio 2011.

Study characteristics
Methods	Study design: parallel RCT Recruitment: May 2003 to February 2007 Study duration: 5 months (follow‐up 2 years)
Participants	Country: Australia Setting: single‐centre; hospital outpatient department Inclusion criteria: ≥ 6 months post kidney transplant; functioning and stable transplant; attend regular follow‐up every 2 or 3 months Number: intervention group (56; 41 overweight or obese); control group (46; 38 overweight or obese) Mean age ± SD (years): intervention group (54.9 ± 9.9) control group (54.7 ± 11.8) Sex (M/F): intervention group (33/23); control group (29/17) Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): intervention group (29 ± 5); control group (29 ± 6) Stage of CKD: transplant recipients Mean baseline eGFR ± SD (mL/min/1.73 m²): intervention group (54 ± 20); control group (48 ± 17) Median baseline SBP, range (mmHg): intervention group (135, 105 to 178); control group (131, 100 to 171) Median baseline DBP, range (mmHg): intervention group (81, 56 to 107); control group )79, 50 to 100) Median baseline energy intake, range) (kJ): intervention group (8334, 5502 to 12,031); control group (8539, 6646 to 12,418) Comorbid conditions: type 2 diabetes mellitus (47%) Exclusion criteria: not reported
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary + exercise Intervention group (lifestyle group) Individualised dietary advice was provided to participants for the duration of the trial. A Mediterranean style (< 30% total energy from fat), low glycaemic index with an energy deficit of 500 kcal/day to promote weight loss was recommended. Physical activity advice was provided participants in line with the Australian National Physical Activity recommendations of 150 minutes of accumulated physical activity each week. The Transtheoretical Model of Health Behaviour Change or Stage of Change Model was a component underpinning the lifestyle intervention. Study manual with dietary information and lifestyle information, food models and pictures was used to teach participants. Individualised dietary advice was provided to participants for the duration of the trial. Physical activity ‐ advice to achieve 150 minutes of accumulated physical activity per week. The intervention was delivered by a multi‐disciplinary team (dietitian, nephrologist, nurse, and endocrinologist).The Transtheoretical Model of Health Behaviour Change or Stage of Change model was a used to provide a framework for goal setting. Control group Received usual standard care Co‐interventions None reported
Outcomes	Body weight (kg) BMI (kg/m²) Waist circumference (cm) Waist‐to‐hip ratio (units) SBP (mmHg) DBP (mmHg) Total cholesterol (mmol/L) LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Triglycerides (mmol/L) Fasting blood glucose (mmol/L) HbA1c (mmol/L) Dietary intake (energy intake kJ/day) Physical activity behaviours (The Physical Activity Statewide Questionnaire)
Notes	Founding source: Allied Health Research Scheme from Queensland Health and an Allied Health Research Scholarship from the Princess Alexandra Hospital Foundation, Brisbane Trial registration: not reported Possible conflicts of interest for study author: not declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	Insufficient information to permit judgement ‐ participants unlikely to be not blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Number of participants who completed the study were not reported
Selective reporting (reporting bias)	Unclear risk	No protocol published. Insufficient information detailing whether treatment outcomes are reported as planned
Other bias	Low risk	Study appears free of other biases

Praga 1995.

Study characteristics
Methods	Study design: parallel RCT Recruitment: enrolment start and finish date not reported Study duration: 12 months
Participants	Country: Spain Setting: single‐centre; obesity outpatient clinic Inclusion criteria: obesity BMI > 30kg/m², proteinuria >1 g/24 hour (on at least 3 consecutive determinations) Number: intervention group (9); control group (8) Mean age ± SD (years): intervention group (47.3 ± 8.0); control group (49.5 ± 12.7) Sex (M/F): intervention group (4/5); control group (2/6) Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): intervention group (1 37.1 ± 3.1); control group (38.2 ± 5.0) Stage of CKD: not reported Mean baseline eGFR ± SD (mL/min/1.73 m²): not reported Mean baseline SBP ± SD (mmHg): not reported Mean baseline DBP ± SD (mmHg): not reported Mean baseline energy intake ± SD (kcal/day): not reported Comorbid conditions: sleep apnoea (29%) Exclusion criteria: diabetes mellitus; systemic disease
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary Intervention group (hypocaloric diet) Were instructed to follow a 1000 to 400 kcal/day diet without a protein restriction. Nil further information on intervention delivery information, who delivered the intervention Control group (captopril without dietary change) Maintained their usual dietary habits without any dietary changes. They started captopril treatment prescribed at 25 mg/day to 50 mg/day in 2 divided doses, to begin with. Later the dose was adjusted according with BP (mean dose 78 mg ± 36 mg/day). Nil further information on intervention delivery information, who delivered the intervention Co‐interventions Not reported
Outcomes	BMI (kg/m²) CrCl (mL/min) SCr (mg/dL) Proteinuria (g/24 hour) Albuminuria (g/dL) Total cholesterol (mg/dL) Triglycerides (mg/dL)
Notes	Founding source: not reported Trial registration: not applicable as published before 2006 Possible conflicts of interest for study author: not declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement ‐ no description of randomisation sequence
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement ‐ no description of allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement ‐ no details on if assessors were blinded or not
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Selective reporting (reporting bias)	High risk	Many reported outcome measures have not been reported adequately
Other bias	Unclear risk	Insufficient information to permit judgement

Teplan 2002.

Study characteristics
Methods	Study design: parallel RCT Recruitment: enrolment start and finish date not reported Study duration: up to 36 months
Participants	Country: Czech Republic Setting: not reported Inclusion criteria: included individuals who were obese BMI ≥ 30 kg/m² and at least 1 year post kidney transplant Number: intervention group (128); control group (130) Age range: 22 to 78 years Sex (M/F): 108/150 Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): not reported Stage of CKD: kidney transplant recipients > 1 year post transplant Mean baseline eGFR ± SD (mL/min/1.73 m²): not reported Mean baseline SBP ± SD (mmHg): not reported Mean baseline DBP ± SD (mmHg): not reported Mean baseline energy intake ± SD (kcal/day): not reported Comorbid conditions: not reported Exclusion criteria: not reported
Interventions	Intervention type classification: mixed (lifestyle + pharmacological) Weight loss intervention/s used: dietary + pharmacological Intervention group (diet group) Individualised low energy and low fat diet + corticoids withdrawal. After 3 months participants were given orlistat at a dose of up to 3 x 120 mg/day and statins for 3 years. Nil further information on who delivered the intervention and what participants received was reported Control group Usual care for up to 3 years. Nil further information on what was usual care Co‐interventions Not reported
Outcomes	BMI (kg/m²) CrCl (mL/s) Proteinuria (units not reported) Fasting blood glucose (mmol/L) Total cholesterol (mmol/L) LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Triglycerides (mmol/L)
Notes	Founding source: IGA ND/5686‐3 Trial registration: not reported Possible conflicts of interest for study author: not declared (no statement provided) Abstract‐only publication
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	Unclear risk	Insufficient information to permit judgement

Teplan 2006.

Study characteristics
Methods	Study design: parallel RCT Recruitment: enrolment start and finish date not reported Study duration: 3 years
Participants	Country: Czech Republic Setting: not reported Inclusion criteria: CKD stages 3 to 4 with eGFR 28 to 48 mL/min/1.73 m²; obese BMI > 30 kg/m²; waist‐to‐hip ratio > 85; good compliance and adherence to a diet for the 4 weeks prior to the start of the study. Metabolic acidosis was corrected in all patients Number: intervention group (66); control group (65) Mean age ± SD: 52 ± 7 years Sex (M/F): 54/57* Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): intervention group (32.0 ± 3.30; control group (31.6 ± 3.9) Stage of CKD: stages 3 to 4 Mean baseline CrCl ± SD (mL/min/1.73 m²): intervention group (36.2 ± 15.4); control group (37.4 ± 16.0) Mean baseline SBP ± SD (mmHg): intervention group (135 ± 10); control group (132 ± 6) Mean baseline DBP ± SD (mmHg): intervention group (90 ± 9); control group (92 ± 7) Mean baseline energy intake ± SD (kcal/day): not reported Comorbid conditions: diabetes mellitus (39%) Exclusion criteria: smoker; history of CVD
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: dietary Intervention group (diet group + keto‐amino acid supplementation) Prescribed a low protein diet 0.6 g/kg/day with energy restriction of 120 to 125 kJ/kg/day for first 6 months and 125 to 130 kJ/kg/day thereafter. Diet was supplemented with keto‐amino acid supplementation (Ketosteril, Fresenius Kabi) at a dose of 100 mg/kg/day The composition of the diet was individualised in terms of taste preferences for participants. Participants were on follow up under balanced conditions for 3 days at baseline and then followed up every 3 months for 3 years. Control group (diet group + placebo) Prescribed a low protein diet 0.6 g/kg/day with energy restriction of 120 to 125 kJ/kg/day for first 6 months and 125 to 130kJ/kg/day thereafter. Diet was supplemented with placebo The composition of the diet was individualised in terms of taste preferences for participants. Participants were on follow up under balanced conditions for 3 days at baseline and then followed up every 3 months for 3 years Co‐interventions All patients had regular treatment with ACEi, ARB and statins
Outcomes	BMI (kg/m²) Waist‐to‐hip ratio (units) Body composition: visceral fat (cm³) and subcutaneous fat (cm³) CrCl (mL/min/1.73 m²) Proteinuria (g/24 hour) Measured GFR (inulin clearance rate) SBP (mmHg) DBP (mmHg) HbA1c (%) Total cholesterol (mmol/L) LDL cholesterol (mmol/L) Triglycerides (mmol/L)
Notes	Founding source: Grant NR/8509‐3 awarded by the Internal Grant Agency of the Czech Republic Trial registration: not provided Possible conflicts of interest for study author: Not declared (no statement provided) * Number of reported males and females (111) does not agree with number randomised (131)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Double blind RCT
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement. Double blind RCT however no information on allocation concealment reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind RCT
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement. It was not reported if the outcome assessors were blind to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement ‐ no information on completion rates
Selective reporting (reporting bias)	Low risk	No study protocol however appear to report on all stated outcomes
Other bias	Unclear risk	Insufficient information to permit judgement

Tomlinson 1975.

Study characteristics
Methods	Study design: cross‐over RCT Recruitment: May to August 1972 (trial 1) and February to May 1973 (trial 2) Study duration: 13 to 15 weeks (5 to 6 weeks for each intervention phase and a 2 to 3 week washout period)
Participants	Country: UK Setting: single centre, hospital outpatient clinic Inclusion criteria: kidney transplant with satisfactory function (this criteria not reported), obesity or cushingoid appearance Number Trial 1: intervention group (5); control group (6) Trial 2: intervention group (8); control group (6) Mean age ± SD (years): not reported Sex (M/F): trial 1 (6/5); trial 2 (8/6) Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI (kg/m²): not reported Stage of CKD: transplant recipients Mean baseline eGFR ± SD (mL/min/1.73 m²): not reported Mean baseline SBP ± SD (mmHg): not reported Mean baseline DBP ± SD (mmHg): not reported Mean baseline energy intake ± SD (kcal/day): not reported Comorbid conditions: 32% of participants had hypercholesterolaemia. Exclusion criteria: oedema; fasting blood glucose level < 90 mg/100 mL
Interventions	Intervention type classification Trial 1: pharmacological + lifestyle Trial 2: pharmacological Weight loss intervention/s used Trial 1: appetite suppressant + dietary Trial 2: appetite suppressant Trial 1 Intervention first group Received placebo medication for 2 to 3 weeks as a run‐in period, followed by 120 mg/day fenfluramine for 5 to 6 weeks followed by placebo medication for 5 to 6 weeks Control first group Received placebo medication for 2 to 3 weeks as a run‐in period, then continued on placebo medication for 5 to 6 weeks. Then given 120 mg/day fenfluramine for 5 to 6 weeks Co‐interventions All participants were given dietary advice at the beginning of the trial and during the in the run‐in period and a dietary assessment was made by a member of the research team. It is not reported what was the dietary advice Trial 2 Intervention first group Received 80mg/day fenfluramine for 5 to 6 weeks, then received placebo medication for 3 weeks followed by placebo medication for 5 to 6 weeks Control first group Received placebo for 5 to 6 weeks, then received placebo medication for 3 weeks, followed by 80 mg/day fenfluramine for 5 to 6 weeks Co‐interventions No dietary advice nor dietary assessments were provided in this trial
Outcomes	Weight loss (kg) Body weight (kg) Total cholesterol (mg/100 mL) Adverse patient outcomes associated with each weight loss intervention BP (mmHg) Triglycerides (mg/100 mL)
Notes	Founding source: not reported Trial registration: not applicable as published before 2006 Possible conflicts of interest for study author: not reported Fenfluramine the appetite suppressant used in this trial, was withdrawn from the market in 1997 due to safety reasons and is no longer approved as a drug
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement ‐ not reported how participants were randomised
Allocation concealment (selection bias)	Low risk	Allocation not revealed until un‐blinding
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo randomised controlled double blind trial
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinded outcome assessors
Incomplete outcome data (attrition bias) All outcomes	High risk	Missing data not well reported, 22% attrition rate
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement ‐ some outcome measures not well reported
Other bias	Low risk	Nil other potential sources of bias identified

Tzvetanov 2015.

Study characteristics
Methods	Study design: pilot RCT Recruitment: enrolment start and finish date not reported Study duration:12 months
Participants	Country: USA Setting: not reported Inclusion criteria: not reported Number: intervention group (4); control group (2) Mean age ± SD (years): intervention group (45 ± 6.50; control group (42.5 ± 4.5) Sex (M/F): not reported Baseline characteristics Nationality: not reported Ethnicity: not reported Mean baseline BMI ± SD (kg/m²): intervention group (39.9 ± 1.4); control group (40.5 ± 0.2) Stage of CKD: post kidney transplant Mean baseline eGFR ± SD (mL/min/1.73 m²): not reported Mean baseline SBP ± SD (mmHg): not reported Mean baseline DBP ± SD (mmHg): not reported Mean baseline energy intake ± SD (kcal/day): not reported Comorbid conditions: not reported Exclusion criteria: not reported
Interventions	Intervention type classification: mixed (bariatric surgery + lifestyle) Weight loss intervention/s used: sleeve gastrectomy compared to standard care weight loss program Intervention group Simultaneous robotic kidney transplant and sleeve gastrectomy. No further information provided on the intervention, who delivered the intervention or how often care or treatment was received post surgery Comparator group Received standard weight loss program after a robotic kidney transplant. Not reported what the intervention consisted of and who delivered the intervention or how often care or treatment was received Co‐interventions Nil reported
Outcomes	BMI (kg/m²) Adverse patient outcomes associated with each weight loss intervention
Notes	Founding source: not reported Trial registration: not reported Possible conflicts of interest for study author: not declared (no statement provided) Abstract only. Preliminary results only
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	Unclear risk	Insufficient information to permit judgement

Woolf 2017.

Study characteristics
Methods	Study design: pilot RCT Recruitment: enrolment start and finish date not reported Study duration: 6 months
Participants	Country: USA Setting: not reported Inclusion criteria: obese or overweight patients with type 2 diabetes and CKD Number: Social Cognitive Theory‐based lifestyle intervention (7); standard behaviour treatment (7) Mean age ± SD: 65.9 ± 9.7 years Sex (% male): 71.4% Baseline characteristics Nationality: not reported Ethnicity: 71.4% of participants were white Mean baseline BMI ± SD: 34.8 ± 5.4 kg/m² Stage of CKD: not reported Mean baseline eGFR ± SD (mL/min/1.73 m²): not reported Mean baseline energy intake ± SD (kcal/day): not reported Mean baseline SBP ± SD (mmHg): not reported Mean baseline DBP ± SD (mmHg): not reported Comorbid conditions: not reported Exclusion criteria: not reported
Interventions	Intervention type classification: lifestyle Weight loss intervention/s used: behavioural Intervention group Social Cognitive Theory‐based lifestyle intervention: group was provided with an iPad to participate in live WebEx sessions with a registered dietitian, access to MyNetDiary (an online tool to log dietary intake, exercise, and body weight) and email feedback from a registered dietitian weekly for the first month and then biweekly for 6 months Control group Standard behaviour treatment group: no further information on what the group received was reported Co‐interventions Nil reported
Outcomes	Weight loss (%)
Notes	Founding source: NIH K24 NR01226 and NIH R01 DK100492 (PI MA Sevick) Trial registration: not reported Possible conflicts of interest for study author: Not declared (no statement provided). Abstract‐only publication
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	Unclear risk	Insufficient information to permit judgement

ACEi ‐ angiotensin‐converting enzyme inhibitors; ACR ‐ albumin‐to‐creatinine ratio; ALT ‐ alanine aminotransferase; ARB ‐ angiotensin receptor blocker; AST ‐ aspartate aminotransferase; BMI ‐ body mass index; BP ‐ blood pressure; CKD ‐ chronic kidney disease; CrCl ‐ creatinine clearance; CVD ‐ cardiovascular disease; DBP ‐ diastolic blood pressure; (e)GFR ‐ (estimated) glomerular filtration rate; Hb ‐ haemoglobin; HbA1c ‐ haemoglobin A1c; HD ‐ haemodialysis; HDL ‐ high‐density lipoprotein; HRQoL ‐ health‐related quality of life; IGAN ‐ Ig A nephropathy; IQR ‐ interquartile range; LDL ‐ low‐density lipoprotein; NSAID ‐ nonsteroidal anti‐inflammatory drug; NYHA ‐ New York Heart Association; PCR ‐ protein:creatinine ratio; RCT ‐ randomised controlled trial; SBP ‐ systolic blood pressure; SCr ‐ serum creatinine

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
ACT 2017	Wrong intervention: not weight loss Intervention
Aliasgharpour 2012	Intervention duration too short (intervention delivered before and after dialysis sessions over a 2‐week period)
BEACON 2013	Wrong intervention: not weight loss Intervention
BEAM 2011	Wrong intervention: not weight loss Intervention
ESPECIAL 2014	Wrong intervention: not weight loss Intervention
INTENT 2014	Wrong intervention: not weight loss Intervention
Jasiak‐Panek 2019	Wrong intervention: not weight loss Intervention
Kincaid‐Smith 2002	Wrong intervention: not weight loss Intervention
Teplan 2000	Wrong intervention: not weight loss Intervention
Teplan 2003b	Wrong intervention: not weight loss Intervention
Teplan 2004	Wrong intervention: not weight loss Intervention
Teplan 2007	Wrong intervention: not weight loss Intervention
Tzvetanov 2014	Wrong intervention: not weight loss Intervention
Zingerman 2015	Wrong intervention: not weight loss Intervention

Characteristics of ongoing studies [ordered by study ID]

HHK 2018.

Study name	Lifestyle management of CKD in obese diabetic patients: The Healthy Hearts and Kidneys (HHK) study
Methods	Design of a 2 x 2 factorial RCT of technology‐supported self‐monitoring and social cognitive theory‐based counselling to engage overweight people with diabetes and CKD in multiple lifestyle changes
Participants	Individuals with type 2 diabetes mellitus and evidence of CKD aged ≥ 40 years, who are overweight/obese BMI ≥ 27.0 kg/m²
Interventions	Participants will be randomised to 1 of 4 groups Usual care (UC) Social Cognitive Theory‐based group counselling (SCT) Mobile self‐monitoring with tailored feedback and counselling (MONITORING) Combination of SCT plus MONITORING conditions (COMBINED)
Outcomes	Primary outcomes Weight reduction Urinary sodium excretion Serum phosphorus Secondary outcomes Physical activity BP Fasting lipids Medication requirements Pulse wave velocity Measurements will occur at baseline, 6 and 12 months
Starting date	October 2014
Contact information	Mary Ann Sevick mary.sevick@nyumc.org
Notes	Clinical trials last updated on 14 July 2020. Recruitment completed

Spaggiari 2020.

Study name	Simultaneous robotic kidney transplantation and bariatric surgery for morbidly obese patients with end‐stage renal failure
Methods	Single centre, open label, prospective, RCT
Participants	Kidney transplant recipients, with a BMI ≥ 35 kg/m²
Interventions	Intervention group Participants in this arm will receive simultaneous robotic assisted kidney transplant and robotic assisted sleeve gastrectomy Control group Participants in this arm will receive a robotic assisted kidney transplant
Outcomes	Body weight loss BMI GFR
Starting date	Not reported
Contact information	Not reported
Notes	Abstract‐only publication

BMI ‐ body mass index; BP ‐ blood pressure; CKD ‐ chronic kidney disease; GFR ‐ glomerular filtration rate; RCT ‐ randomised controlled trial

Differences between protocol and review

Measured GFR was included as an outcome measure.

Contributions of authors

1. Draft the protocol: MC, CM, KC, HM, DJ

2. Study selection: MC, CM

3. Extract data from studies: MC, HM, CM

4. Enter data into RevMan: MC, JK

5. Carry out the analysis: MC, JK,

6. Interpret the analysis: MC, JK, CM, KC, HM, DJ

7. Draft the final review: MC, JK, CM, KC, HM, DJ

8. Disagreement resolution: KC

9. Update the review: MC

Sources of support

Internal sources

• Nil sources of support provided, Other

External sources

• No sources of support supplied

Declarations of interest

• Marguerite Conley: none known

• Catherine McFarlane: none known

• David Johnson: none known

• Katrina Campbell: none known

• Helen MacLaughlin: has received consultancy fees, lecturing fees and support for travel expenses from Abbott Nutrition, Nestle

• Jaimon Kelly: none known

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