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. 2023 May 20;14(7):1111–1136. doi: 10.1007/s13300-023-01416-2

Optimizing Multidisciplinary Care of Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus

Ellie Kelepouris 1,, Wendy St Peter 2,3, Joshua J Neumiller 4, Eugene E Wright 5
PMCID: PMC10241769  PMID: 37209236

Abstract

Diabetes is the leading cause of chronic kidney disease (CKD), a condition associated with significant morbidity and mortality. As these patients have a high risk of developing cardiovascular disease and end-stage kidney disease, there is a need for early detection and early initiation of appropriate therapeutic interventions that slow disease progression and prevent adverse outcomes. Due to the complex nature of diabetes and CKD management, a holistic, patient-centered, collaborative care approach delivered by a coordinated multidisciplinary team (ideally including a clinical pharmacist as part of a comprehensive medication management program) is needed. In this review, we discuss the barriers to effective care, the current multidisciplinary approach used for CKD prevention and treatment, and the potential ways that the multidisciplinary management of CKD associated with type 2 diabetes mellitus can be refined to improve patient outcomes.

Keywords: Chronic kidney disease, Type 2 diabetes mellitus, Multidisciplinary care, Multidisciplinary team, Care optimization, Prevention

Plain Language Summary

People living with type 2 diabetes mellitus are at risk of developing chronic kidney disease. Having chronic kidney disease means that over time the kidneys may not work as well as they should. Some people with chronic kidney disease will eventually need a new kidney (transplant) or will need to use a machine that does the job of their kidneys (dialysis). To slow the rate at which the kidneys get worse, chronic kidney disease needs to be detected and treated early. A multidisciplinary team of healthcare professionals is needed to help people with type 2 diabetes reduce their chances of getting chronic kidney disease, or to prevent their chronic kidney disease from getting worse. Some healthcare teams include a clinical pharmacist who makes sure medicines are given in the correct amount and at the correct time. It is important that the healthcare team members communicate well and include the person with type 2 diabetes and chronic kidney disease and their family members or caregivers (if needed) in the decision-making process to achieve better health results. Barriers stopping people with type 2 diabetes and chronic kidney disease from getting good healthcare include a shortage of nephrologists, not having enough healthcare insurance, limited access to healthcare, and poor understanding about what chronic kidney disease is and how it can be treated. This review article discusses the barriers to better healthcare in chronic kidney disease and how the current healthcare team approach could be changed to improve health results.

Graphical Plain Language Summary

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Key Summary Points

Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are chronic conditions associated with long-term health, financial, and quality-of-life consequences for patients.
Barriers to optimized CKD care in people with T2DM include a shortage of specialist clinicians (nephrologists), delays in initiation or appropriate adjustment of evidence-based therapies, inconsistent screening practices, poor health literacy, inadequate healthcare insurance coverage, and limited access to healthcare.
An effective and well-coordinated multidisciplinary team (MDT), especially one that includes a clinical pharmacist as part of a comprehensive medication management (CMM) program, should proactively address many of these barriers to effective care.
Implementation of a collaborative care MDT approach (incorporating CMM) for CKD associated with T2DM across the USA is recommended.

Digital Features

This article is published with digital features, including a graphical plain language summary, to facilitate understanding of the article. To view digital features for this article go to https://doi.org/10.6084/m9.figshare.22644406.

Introduction

An estimated 37.3 million people in the USA have diabetes, which equates to 11.3% of the general population [1]. Approximately one in three adults with diabetes will develop chronic kidney disease (CKD) in their lifetime [2]. Diabetes is the leading cause of CKD and accounts for approximately 40% of end-stage kidney disease (ESKD) cases [3, 4]. Furthermore, advanced-stage CKD (stages 4 and 5) is associated with significant morbidity and mortality, predominantly due to the development of ESKD and associated cardiovascular disease (CVD) [5]. Furthermore, according to the US Centers for Disease Control and Prevention (CDC), of US adults diagnosed with advanced-stage CKD between 2017 and 2020, the prevalence of diabetes (including pre-diabetes) was 36.1%, compared with 3.6% of adults having advanced-stage CKD and no diabetes [6]. Where CKD was noted as the cause of death in the Global Burden of Disease study in 2017, 28.4% of these deaths were in patients who had type 2 diabetes mellitus (T2DM) [7]. In a separate analysis using data from the third National Health and Nutrition Examination Survey (NHANES III), the presence of diabetes and kidney disease was shown to impart an almost sixfold greater risk of cardiovascular (CV) mortality compared to those without these conditions [8]. It is clear from these data that diabetes is an important risk factor for developing CVD and CKD. Indeed, deaths attributable to CVD due to impaired kidney function caused 4.6% of global deaths in 2017, making CKD the 12th leading cause of death globally [5].

Early diagnosis and initiation of appropriate treatments are needed to slow the progression of CKD and to prevent adverse outcomes [5, 9]. A coordinated multidisciplinary team (MDT) approach that involves shared decision-making with patients is needed to optimize this process and ensure that patients receive guideline-directed medical therapy in order to reduce CKD progression and improve CV outcomes. In this article, we review the current approach to the prevention and treatment of CKD and evaluate how the multidisciplinary management of CKD can be further refined.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Multidisciplinary Team Approach to Chronic Kidney Disease Prevention in Patients with Type 2 Diabetes Mellitus

An MDT approach is critically important in patients with T2DM, as such a collaboration will help reduce a patient’s risk of developing CKD or risk of advancing disease. Indeed, patients often benefit from being at the center of a well-coordinated MDT of healthcare professionals (HCPs) [10]. Although having T2DM is a risk factor for developing CKD, additional risk factors include obesity, a diet high in cholesterol and salt, hypertension, and poor glycemic control [11]. An effective MDT will encourage patients with T2DM to make lifestyle/behavioral modifications that mitigate such risks [12, 13]. For glycemic control, an individualized glycated hemoglobin (HbA1c) target of ≤ 6.5% to < 8% is recommended based on patient factors, such as the number of comorbidities or increased burden of hypoglycemia; in addition, a routine office blood pressure reading of < 130/80 mmHg is also recommended [12, 14, 15].

The roles within the MDT supporting patients with T2DM may include diabetes care and education specialists, primary care and subspecialty clinicians, nurses, dietitians, exercise specialists, clinical pharmacists, dentists, podiatrists, and mental health professionals [16]. Intrinsic to a successful MDT–patient collaboration is a medical team who effectively communicate with, support, and educate their patients with diabetes about their personal CKD risk and CKD risk mitigation. It is essential that these communication strategies are implemented early following a diabetes diagnosis [17]. Communicating clearly that their risk can be reduced but not totally eliminated [17] is an important aspect of this. There are several risk-reduction measures a patient with T2DM can use to reduce their risk of progressive CKD. As noted briefly, lifestyle and behavioral modifications play an integral role in diabetes management and CKD prevention and are recommended as part of a holistic approach to T2DM care [12, 18]. The recommended lifestyle modifications for people with T2DM include weight management, regular exercise, smoking cessation, limiting alcohol consumption, and eating a healthy, balanced, and low-sodium diet to optimize blood pressure and reduce the risk of a CV event [14, 19]. As part of this strategy, optimization of the HbA1C, blood pressure, and low-density lipoprotein cholesterol levels (through lifestyle modification and medicine use) are recommended to prevent microvascular and macrovascular complications of T2DM [19, 20].

Changing one’s diet, stopping bad habits, and adopting new CKD (and CVD) risk-reducing behaviors can be difficult. To facilitate implementation of long-term lifestyle changes, individualized medical nutrition therapy should be delivered to patients from the time of their T2DM diagnosis by a trained registered dietitian, certified nutritionist, or knowledgeable clinician, with periodic re-education as needed [14]. In addition, diabetes self-management education and support should be initiated at T2DM diagnosis and continued as required [14]. Alongside preventative interventions, patients should continue to meet with their primary care clinician (although for some patients this may be their endocrinologist) every 3 to 6 months for regular CKD risk factor re-assessments [12]. Screening for albuminuria using a spot urine test to determine the urine albumin-to-creatinine ratio (UACR) and the estimated glomerular filtration rate (eGFR) should be initiated early following a T2DM diagnosis, with annual monitoring [21, 22]. The UACR and eGFR can be used to determine CKD progression risk (Fig. 1) [12]. These screening measures have identified a large cohort of patients at risk for CKD [12].

Fig. 1.

Fig. 1

American Diabetes Association-Kidney Disease: Improving Global Outcomes (ADA-KDIGO) heatmap classifying the risk for CKD progression using GFR and albuminuria measurement categories. Level of risk for CKD progression is indicated by the color of the box, with green indicating low risk (if no other markers of kidney disease present, no CKD), yellow indicating moderately increased risk, orange indicating high risk, and red indicating very high risk. CKD chronic kidney disease, GFR glomerular filtration rate.

Figure is taken from de Boer et al. [12], under a CC-BY license

Most patients with T2DM are managed in primary care unless they develop T2DM-related complications. For example, if a patient has resistant hyperglycemia despite receiving recommended treatments, and/or resistant hypertension despite receiving recommended treatments, and the primary care clinician does not have the relevant experience or time capacity to manage these escalations, then the patient may be referred for specialist assessment. In the same context, for example, a patient with resistant hyperglycemia may be referred to an endocrinologist for evaluation [23] and/or a patient with continuously increasing UACR and/or continuously decreasing eGFR should be referred to a nephrologist [20]. Such referrals may be based on clinical practice guideline recommendations. However, it is important to note that although guidelines are evidence based, the recommendations provided cannot always be applied to clinical practice because real-world factors, such as a local shortage of endocrinologists or nephrologists, may be a reality for some communities; consequently, in situations such as these, the management of care of patients in primary care should be optimized [24, 25]. This also means that the size of the MDT working with a patient with diabetes will be different for similar patients because it will be impacted by factors such as resources, staffing, HCP experience, cost, and location.

Multidisciplinary Team Approach to Reducing Risk of Chronic Kidney Disease Progression in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease

Assuming there are no significant barriers to referrals, patients with T2DM receiving a CKD diagnosis (particularly a diagnosis of CKD stages 3–5) will probably work with an MDT who includes a specialist clinician as well as continue to receive ongoing care from primary care. This expanded team is probably the ideal situation. Indeed, the recent American Diabetes Association (ADA)–Kidney Disease: Improving Global Outcomes (KDIGO) consensus report recommends a MDT-based integrative approach (particularly for those with stages 3–5 CKD) [12]. Furthermore, MDTs in CKD care are associated with improved outcomes for patients with advanced-stage CKD versus alternatives (non-MDT) care approaches. Two separate systematic reviews found that MDTs in CKD care were associated with a reduced risk of all-cause mortality and temporary catheterization for dialysis [10, 26], and possibly also a reduced risk of hospitalization [10], versus non-MDT care. MDTs are also associated with a risk reduction of 36% for kidney replacement in patients with advanced CKD versus non-MDT care [27]. MDTs also appear to have cost benefits versus non-MDT care [27]. The specialist clinicians within the MDT caring for a patient with CKD will probably include a nephrologist (usually for patients with CKD stages 4–5) and possibly other specialists (if not already included), such as a cardiologist and/or endocrinologist if the patient has ongoing resistant hyperglycemia and/or comorbid CVD (both are also risk factors for CKD progression). Indeed, the average MDT involved in CKD care is composed of four members (plus the patient), with a nephrologist the most common non-primary care team member [28].

Primary care clinicians are usually a constant in a patient’s T2DM and CKD journey and play a key role in the early management [29, 30], early detection and monitoring of CKD. It is important to note that in the USA, around 25% of adults do not have an identified source of primary care, so these individuals need to find an alternative source of healthcare provision as needed [31]. As CKD often occurs in conjunction with diabetes, and with other comorbid conditions, care for these patients is typically multidisciplinary in nature, and primary care providers are well positioned to provide holistic care to patients with mild-to-moderate CKD [29]. The holistic approach includes patient-centered drug therapy, which may include prescribing metformin for blood glucose control (particularly within the first year following a T2DM diagnosis) and/or a renin–angiotensin-system (RAS) inhibitor for blood pressure control (as well as reducing risk of CKD progression) and statins to lower blood cholesterol (high cholesterol being a risk factor for CVD) (Fig. 2) [12].

Fig. 2.

Fig. 2

ADA-KDIGO holistic approach for improving outcomes in patients with diabetes and CKD. *ACEis or ARBs should be first-line therapy for HTN when albuminuria is present, otherwise dihydropyridine-type CCBs or diuretic can also be considered; all three classes of medication are often needed to attain BP targets. Finerenone is currently the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits. If eGFR is 30–44 mL/min/1.73 m2, initiate metformin at half the recommended dose (for immediate or extended release formulations), and titrate upwards to half of maximum recommended dose if tolerated. If eGFR is < 30 mL/min/1.73 m2, stop metformin, or do not initiate metformin. Monitor kidney function (at least every 3–6 months) with GFR < 60 mL/min/1.73 m2. Initiate monitoring for possible B-12 deficiency when persons are treated with metformin for > 4 years. Icons presented represent the following benefits: BP cuff indicates blood pressure–lowering; glucometer indicates glucose-lowering; heart indicates heart protection; kidney indicates kidney protection; scale indicates weight management. ACEi angiotensin-converting enzyme inhibitor, ACR albumin-to-creatinine ratio, ARB angiotensin II receptor blocker, ASCVD atherosclerotic cardiovascular disease, BP blood pressure, CCB calcium channel blocker, CVD cardiovascular disease, eGFR estimated glomerular filtration rate, GLP-1 RA glucagon-like peptide-1 receptor agonist, HTN hypertension, MRA mineralocorticoid receptor antagonist, PCSK9i PCSK9 inhibitor, RAS renin-angiotensin system, SGLT2i sodium-glucose cotransporter 2 inhibitor, T1D type 1 diabetes, T2D type 2 diabetes.

Adapted from de Boer et al. [12], under a CC-BY license

Early identification and management of CKD is needed to prevent CKD progression and CV events. CKD treatment guidelines provide recommendations about how and when to screen for CKD as well as test result thresholds for referrals, and the relevance of these recommendations has been reported previously. However, many clinical practices have not incorporated these recommendations. Early detection, usually within the primary care setting, reduces the risk of progression and risk of requiring kidney replacement therapy (dialysis or transplantation) [29], which is expensive and can have significant health status and quality-of-life implications for a patient.

Primary care clinicians typically focus on managing modifiable risk factors in patients with T2DM and CKD, including blood pressure, blood glucose levels, and albuminuria, as well as monitoring kidney function and coordinating care [29, 32]. However, it is typically the role of specialists, such as nephrologists, to consider treatment and associated CV risk in patients with advanced CKD [29]. Patient transition from primary to secondary specialist care usually occurs following referral from a primary care clinician; therefore, the latter are often considered gatekeepers to further care [33]. When a patient with T2DM visits their primary care clinician, if all confirmatory kidney screening tests point to CKD, they should be referred to a nephrologist [34], particularly when the test results show UACR > 300 mg/g and/or eGFR < 30 mL/min/1.73 m2. Although the criteria for when this should happen are included in the ADA-KDIGO 2022 consensus report [12] (Fig. 1), it is important to consider the practitioner’s comfort level with the management and treatment of these patients.

Current Drug Treatment for Chronic Kidney Disease Associated with Type 2 Diabetes Mellitus: Clinical Practice Guideline Recommendations

As CKD is not curable, the main aim of treatment is to reduce the risk of CKD progression and to reduce CV complications [35]. Recommended therapies for CKD associated with T2DM (including angiotensin-converting enzyme inhibitors [ACEis]/angiotensin receptor blockers [ARBs] and sodium-glucose cotransporter-2 inhibitors [SGLT2is]) are underprescribed [6, 36], thus substantiating the importance of team-based treatment to increase screening, identification, and early initiation of evidence-based therapies. Generally, for patients with severely increased albuminuria (UACR ≥ 300 mg/g), a reduction of ≥ 30% in UACR (mg/g) is recommended to slow CKD progression [20]. Table 1 provides a summary of the current 2023 ADA [20] and 2022 KDIGO [15] clinical practice guideline recommendations for ACEis/ARBs, SGLT2is, and nonsteroidal mineralocorticoid receptor antagonist (MRA) (finerenone) use in CKD associated with T2DM, as well as a summary of relevant clinical trial history for these three drug classes.

Table 1.

American Diabetes Association (2023)-Kidney Disease: Improving Global Outcomes (2022) guideline recommendations and clinical trial history regarding the initiation of renin–angiotensin–aldosterone system inhibitors, sodium-glucose cotransporter 2 inhibitors, and/or nonsteroidal mineralocorticoid receptor antagonist (finerenone) for patients with chronic kidney disease-associated with type 2 diabetes mellitus

Clinical trial history
Drug class ADA 2023/KDIGO 2022 guideline recommendationsa Completed phase III clinical trials Key kidney/CV outcome(s) Key inclusion criteria
RAASis (ACEis and ARBs)

Nonpregnant patients with diabetes and hypertension:

 ADA 2023: Use if albuminuria (UACR ≥ 300 mg/g) and/or eGFR < 60 mL/min/1.73 m2) (ADA, 2023)

 KDIGO 2022: Use if albuminuria and titrated to the highest tolerated dose (KDIGO, 2022)

Irbesartan

(Parving et al. 2001 [38])

Time to the onset of diabetic nephropathy Hypertensive patients with T2DM, persistent albuminuria, serum creatinine concentration ≤ 1.5 mg/dL (men) or ≤ 1.1 mg/dL (women)

Telmisartan

(Makino et al. 2007 [39])

Transition rate from incipient to overt nephropathy; microalbuminuria remission Patients with T2DM and UACR 100–300 mg/g and serum creatinine < 1.5 mg/dL (men) and < 1.3 mg/dL (women)

Losartan

(Brenner et al. 2001 [40])

Composite of doubling of baseline serum creatinine concentration; end-stage renal disease or death Patients with T2DM and nephropathy, urinary albumin ≥ 300 mg/L, and serum creatinine values between 1.3 and 3.0 mg/dL

Captopril

(Lewis et al. 1993 [41])

Doubling of the baseline serum creatinine concentration to at least 2.0 mg/dL; length of time to the combined end points of death, dialysis, and transplantation and changes in renal function Insulin-dependent diabetes mellitus for at least 7 years, diabetes onset before age 30 years, diabetic retinopathy, urinary protein excretion of ≥ 500 mg per 24 h, and serum creatinine concentration of ≤ 2.5 mg/dL
SGLT2is

CKD associated with T2DM:

 ADA 2023: Use to reduce CKD progression and CV events if eGFR ≥ 20 mL/min/1.73 m2 and UACR is ≥ 200 mg/g; or an optionb if eGFR ≥ 20 mL/min/1.73 m2 to reduce risk of CV events (ADA, 2023)

 KDIGO 2022: Use if eGFR ≥ 20 mL/min/1.73 m2 (KDIGO, 2022)c

Canagliflozin

CANVAS program (Neal et al. 2017 [42])

ClinicalTrials.gov: NCT01032629 and NCT01989754

Composite of sustained 40% reduction in eGFR, kidney replacement therapy, or death from kidney Patients with T2DM plus established CVD or risk factors for CV events, eGFR of ≥ 30 mL/min/1.73 m2 at screening, presence of microalbuminuria or macroalbuminuria

Canagliflozin

CREDENCE

(Perkovic et al. 2019 [43])

ClinicalTrials.gov: NCT02065791

Composite endpoint of ESKD, doubling of serum creatinine, or death from renal or CV causes Patients with T2DM and CKD, glycated hemoglobin level of 6.5–12.0%, eGFR 30 to < 90 mL/min/1.73 m2

Dapagliflozin

DAPA-CKD

(Heerspink et al. 2020 [44])

ClinicalTrials.gov: NCT03036150

Composite endpoint of sustained decline in eGFR of at least 50%, ESKD, or renal/CV death Patients with or without T2DM, eGFR 25–75 mL/min/1.73 m2, UACR (with albumin measured in milligrams and creatinine measured in grams) of 200–5000

Empagliflozin

EMPA-REG OUTCOME

(Zinman et al. 2015 [45])

ClinicalTrials.gov: NCT01131676

Composite endpoint of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke Patients with T2DM and established CVD, eGFR of ≥ 30 mL/min/1.73 m2, glycated hemoglobin level of at least 7.0% and no more than 9.0%

Empagliflozin

EMPA-KIDNEY

(EMPA-KIDNEY Collaborative Group, 2022 [46])

ClinicalTrials.gov: NCT03594110

Progression of kidney disease, death from renal or CV causes Patients with CKD, eGFR of at least 20 but < 45 mL/min/1.73 m2, regardless of the level of albuminuria or with an eGFR of 45 but < 90 mL/min/1.73 m2 with UACR ≥ 200 at screening, on ACEi or ARB treatment
Nonsteroidal MRAs (finerenone)

CKD associated with T2D:

 ADA 2023: Use if albuminuria and increased risk of CKD progression and/or CV events; or an optionb if eGFR ≥ 25 mL/min/1.73 m2 to reduce risk of CV events (ADA, 2023)

 KDIGO 2022: Use if eGFR ≥ 25 mL/min/1.73 m2, normal serum potassium, and albuminuria (≥ 30 mg/g) despite maximum tolerated dose of RAASi (KDIGO, 2022)

Finerenone

FIDELIO-DKD

(Bakris et al. 2020 [47])

ClinicalTrials.gov: NCT02540993

Composite of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure and composite of kidney failure, a sustained decrease ≥ 40% in GFR, renal death Patients with T2DM and CKD and persistent moderate/severe albuminuria, prior treatment with an ACEi/ARB

Finerenone

FIGARO-DKD

(Pitt et al. 2021 [48])

ClinicalTrials.gov: NCT02545049

Composite of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure and composite of kidney failure, sustained decrease ≥ 40% in GFR, renal death Patients with T2DM and CKD and persistent moderate/severe albuminuria, prior treatment with an ACEi/ARB

ACEi angiotensin-converting enzyme inhibitor, ADA American Diabetes Association, ARB angiotensin receptor blocker, CKD chronic kidney disease, CV cardiovascular, eGFR estimated glomerular filtration rate, ESKD end-stage kidney disease, GFR glomerular filtration rate, GLP-1 RA glucagon-like peptide-1 receptor agonist, KDIGO Kidney Disease: Improving Global Outcomes, MRA mineralocorticoid receptor antagonist, RAASi renin–angiotensin–aldosterone system inhibitor, SGLT2i sodium-glucose cotransporter 2 inhibitor, T2DM type 2 diabetes mellitus, UACR urine albumin-to-creatinine ratio

aFor ADA 2023/KDIGO 2022 guideline recommendations, see references [15, 16, 1921, 37]

bOptions for additional CV protection in patients with CKD associated with T2DM per recommendation 11.5c of ADA 2023 guidelines are: an SGLT2i if eGFR is ≥ 20 mL/min/1.73 m2; a GLP-1 RA or nonsteroidal MRA (finerenone) if eGFR is ≥ 25 mL/min/1.73 m2

cKDIGO 2022 guidelines also recommend metformin (first-line; Fig. 2) for blood glucose control for CKD and T2D (if eGFR is ≥ 30 mL/min/1.73 m2) due to CV protective effects; a GLP-1 RA can also be used to achieve individualized glycemic targets (KDIGO, 2022). In the ADA 2023 guideline recommendations, metformin is not included as a recommended/first-line treatment for glycemic control in patients with CKD + T2DM (ADA, 2023)

Barriers to Effective Multidisciplinary Team Coordination in Chronic Kidney Disease Associated with Type 2 Diabetes Mellitus

There are clearly benefits of MDT working to improve outcomes for patients with T2DM and CKD, but there are many barriers to effective MDT collaboration in the setting of CKD (Table 2).

Table 2.

Barriers to effective multidisciplinary treatment of chronic kidney disease

Type of access barrier Issue
Patient-level barriers Asymptomatic disease
Lack of knowledge of symptoms and disease
Poor adherence to treatment
Affordability of treatment
Individual treatment preferences
Insurance complexity
Conflicting information from different HCPs
Patients forced to provide own care coordination
Provider-level barriers HCPs’ limited knowledge of and recognition of CKD and CKD management
HCPs’ lack of awareness of guidelines and treatment algorithms or strict adherence to guidelines when not always appropriate
Difficulty in managing risk factors (e.g. blood pressure, diabetes, obesity)
Belief that CKD is not reversible
Concerns about side effects of drugs (e.g. hyperkalemia)
Explicit or implicit biases
System-level barriers Limited time to care for patients
Shortages of specialist HCPs
Poor reimbursement for delivering optimal care
Need for prior authorizations of drugs
Lack of comprehensive integrated clinical information systems
Lack of clinical support tools and resources to support patient self-management
Issues with availability of treatments
Healthcare and medication-related disparities

Table is adapted from Sperati et al. [52]

HCP healthcare professional

Staff Shortages

In a 2021 report, the Association of American Medical Colleges estimated a shortfall of between 7800 and 48,000 primary care clinicians and between 21,000 and 77,100 specialist clinicians (including nephrologists) by 2034 in the USA [49]. Global shortages in the nephrology workforce (e.g. clinicians, kidney specialist surgeons, and nephrology nurses) have also been reported [50, 51]. Such staff shortages may negatively impact MDT collaboration and contribute to primary care services being overwhelmed with advanced CKD cases. For example, some primary care clinicians have reported that they lack CKD knowledge (particularly on advanced CKD) and lack experience in identifying CKD and in managing advanced stages of the disease, particularly if patients have complex comorbidities [52]. In these circumstances, primary care providers will want to collaborate with or refer patients to specialist care, but staff shortages in nephrology/specialist care (depending on location) create a barrier to care [53].

Treatments

Treatment guidelines for T2DM and CKD provide an evidence-based resource for HCPs that supports clinical decision-making. However, it is important to remember that treatment guidelines may be dissociated from actual clinical practice behavior, and by themselves, they are unlikely to change practice processes. Additionally, such guidelines have been discordant on some key issues, making it difficult for the practitioner decision-making process.

Delays in drug initiation (including drug underuse) in CKD are due to one or a multitude of factors, such as clinical inertia, low CKD awareness, comorbid illness, fragmented CKD care [54], local practice processes, patient preference, issues with drug availability, clinician concerns about possible side effects, cost, and nonmedical factors (social determinants), such as race, lack of insurance, lack of education, and/or low socioeconomic status [52, 55, 56]. For example, although ACEis and ARBs are primarily used to treat hypertension, they have also shown benefit when used for conditions such as heart failure and CKD, independent of their effect on blood pressure [57]. However, despite the proven kidney-protective effect of these drugs, concerns regarding risks of hyperkalemia and a rise in serum creatinine level has led to underusage of these drugs by patients who may benefit from them [57]. Indeed, underuse [58] and underdosage [59] of ACEis and ARBs has been reported. Additionally, a nationwide database study containing patient-level claims and integrated clinical information found that acute kidney injury, hyperkalemia, advanced CKD, and lack of nephrology care services were associated with discontinuation of ACEi/ARB treatment in patients with proteinuric CKD, despite guideline recommendations [60]. Such issues may also underpin the underuse of new evidence-based medicines in CKD that have demonstrated efficacy in clinical trials. Indeed, the study by Hao et al. found that SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were less likely to be prescribed to patients with pre-existing CVD, heart failure, and/or CKD, with reasons being medication coverage, uncertainty about potential harms, and discomfort in prescribing these drugs to medically complex patients [61]. Furthermore, it has been suggested that the nonsteroidal MRA finerenone may be underused in patients with CKD due to clinician concerns about hyperkalemia risk [62]. However, for most patients, hyperkalemia can be managed without the patient having to permanently discontinue finerenone or ACEi/ARB treatment [6365].

Issues during the process by which HCPs obtain prior authorization so patients can access services/treatments on their current healthcare plans poses an obstacle to timely CKD treatment initiation. In the 2021 American Medical Association survey, 88% of clinician respondents stated that the administrative burden of the prior authorizations process resulted in interruptions in chronic treatment for patients and interfered with continuity of care [66]. Additionally, clinicians reported experiencing care delays, abandonment of treatment (by patients), and serious adverse events for patients in their care because of issues in the prior authorization processes [67]. Thus, prior authorization issues can compound the complexities of medication management in patients with CKD.

Cost and Healthcare Insurance Plan Barriers

Having no healthcare insurance or a non-comprehensive healthcare plan is a barrier to accessing treatments for some patients with CKD and T2DM. However, even when a healthcare plan covers most new drugs in the year following their Food and Drug Administration approval (US FDA), patients’ access to these drugs may still require prior authorization or step therapy [68]. Additionally, chronic disease is associated with high healthcare utilization [69] and, as a result, patients may incur high out-of-pocket expenses [70], which may prevent them from accessing certain drug treatments with demonstrated clinical efficacy. For example, results from a retrospective cohort study found that dialysis patients on Medicare Part D who needed to pay a higher co-payment upon reaching the coverage gap were significantly less likely to adhere to drug treatment and persist on their treatment plan due to significant out-of-pocket costs they incur, which is a major concern given the complex medical needs of these patients [71]. Many patients receiving hemodialysis, and some older adults with CKD receiving Medicare benefits, may be eligible for the Part D low-income subsidy (LIS) that covers part or almost all Part D medication costs depending on a patient’s income and assets [4]. However, Medicare patients without the LIS can experience high premiums and co-payments. Many pharmaceutical companies offer patient assistance programs (PAPs) and/or discount cards for brand-name drugs for patients that have limited income or assets, but the requirements, paperwork, and length of the approval process for PAPs is often overwhelming for both patients and practitioners [72]. The complexities of insurance and extra help programs contribute to treatment delays or treatment discontinuation.

Patients

Around 25% of people with CKD have limited health literacy, which disproportionally affects those with low socioeconomic status and of non-white race [73]. Limited health literacy in patients with CKD has been associated with adverse clinical outcomes, increased healthcare utilization, and mortality [73]. Patients who have limited awareness and understanding of their CKD diagnosis and the implications of their diagnosis in terms of drug treatments, progression risks, and lifestyle choices represent a barrier (as perceived by primary care clinicians) to optimal management of CKD due to poor self-management [52]. Furthermore, poor health literacy in patients with CKD contributes to poor treatment adherence, which is another barrier to optimal management of CKD [52, 74]. Addressing patients’ beliefs about drug treatment options (good and bad), teaching them about their conditions and how their medication(s) work at a level they understand, and empowering them to be actively involved in the decision-making processes should facilitate treatment adherence by patients with CKD [75]. Indeed, it is important that HCPs direct their efforts to ensuring their patients feel empowered about their CKD through education and openness as this improves patient engagement, an essential aspect for true shared decision-making between patient and clinician [15]. Shared decision-making between members of the MDT and the patient has been associated with many benefits, including improved treatment adherence [76], patients’ satisfaction with their healthcare [77], patient-provider communication, and patient knowledge [78], as well as reduced healthcare costs (due to reduced hospitalizations/surgeries) [79].

Pharmaco-inequity is a national treatment concern and represents a key barrier to optimal treatment and management of CKD [80]. Disparities in the initiation and use of guideline-recommended treatments, such as SGLT2is and GLP-1 RAs, in patients with CKD and T2DM have been observed [81, 82]. These studies found that African American patients were significantly less likely to start SGLT2i or GLP-1 RA treatment compared with white patients. Furthermore, black race was associated with lower use of newer agents with demonstrated CV/kidney benefits and lower hypoglycemia risk; black race was also associated with a greater risk of patients developing hypoglycemia compared with patients of white race [82]. Such observations regarding the disparities in healthcare interventions for African Americans with CKD demonstrate the urgent need for greater intervention to reduce these disparities in communities of color with CKD in the USA [80].

Improving the Multidisciplinary Care of Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus

Due to the heterogeneity of multidisciplinary CKD clinics, it remains unclear which aspects of multidisciplinary CKD care are most important for positive outcomes in patients [28], although what is clear is that effective MDT collaboration is important. More research is needed to identify the optimal structure and function of MDT in CKD and T2DM care management.

Shared Decision-Making

Comprehensive care, including shared decision-making, is advocated as the most appropriate model for patient-centered care [12]. Patients and HCPs should therefore work collaboratively (as part of an MDT) to make decisions that will be clinically appropriate and suitable for the patient, focusing on the patient’s medication and health-related priorities [83]. If required, a patient’s family members and/or caregivers should also be included in shared decision-making [84]. This patient-centric model of care aims to actively engage and empower patients with CKD by promoting self-management, thus helping patients to achieve their treatment goals [12]. The careful consideration and selection of treatment based on drug effectiveness and drug safety profiles is also warranted and is the approach used in treatment guidelines. Additionally, it is important to consider factors such as treatment accessibility for these patients, including drug cost and coverage and whether a prior authorization is required. Treatment decisions should also consider the differential pharmacological effects as well as safety issues of drugs when evidence-based combination therapy may be necessary. For example, the nonsteroidal MRA finerenone has a distinct mode of action from either an ACEi/ARB or SGLT2i and has a lower hyperkalemia risk than steroidal MRAs [85], and so it would be reasonable to consider use of the former in a high-risk patient with CKD plus T2DM who is already taking the maximally tolerated dose of an ACEi/ARB and an SGLT2i but still has albuminuria [12] (Fig. 1). For patients taking finerenone, practitioners should monitor serum potassium levels to check for possible hyperkalemia (although hyperkalemia can be managed in most patients), as well as monitoring kidney function.

Coordination of Care

Care coordination involves organizing patient care activities and efficiently communicating patient care information between all members of the patient’s care team, with the ultimate goal of achieving safer and more effective care for the patient [86]. Effective care coordination focuses on the total healthcare needs of the patient. There is an urgent need to address suboptimal care coordination between members of the MDT that spans primary and secondary care settings in order to improve care for patients with CKD [87]. Indeed, it is important that each member of the MDT understands what their role is in the coordinated care process in order not to overwhelm the patient with (oftentimes conflicting) [52] information. Without effective care coordination, there is a risk of delivering fragmented and duplicative patient care, which can result in unnecessary additional healthcare costs [88]. In 2021, Kidney Care Partners published principles for care coordination of patients with CKD (non-dialysis, dialysis, and transplant) [89]. These principles include maintaining a patient-centered focus while enhancing the care-giving capabilities of healthcare providers, improving health disparities by focusing on gaps in care, facilitating care transitions, providing clear and consistent education to facilitate patient decision-making, promoting adherence to treatment, and removing barriers for clinicians, providers, and facilities to share information [89].

Education for Healthcare Professionals

There is a need for increasing the awareness and education of primary care practitioners (clinicians, nurse practitioners, and clinical pharmacists), specialty practitioners in cardiology, and endocrinology/diabetes clinics concerning the early-stage identification and diagnosis of CKD. Community pharmacists could deploy point-of-care testing for serum creatinine and UACR in patients at high risk for CKD in order to amplify screening efforts. Concerted efforts are needed to address this issue because an estimated 90% of US adults with CKD do not know they have CKD [2]. In a 2017 survey involving 125 countries, it was noted that clinician knowledge and attitude were key barriers to optimal kidney disease care [90]. Education regarding treatment options, treatment guideline recommendations, and management of adverse events such as hyperkalemia (including re-initiation of therapy following hyperkalemia management) is also needed.

HCPs who work with patients with CKD should also receive (as needed) training on co-management of kidney/heart/diabetes medication management. Currently, the nonprofit Advancing Kidney Disease through Optimal Medication Management initiative is creating a curriculum for practicing clinicians to provide comprehensive medication management (CMM) for patients with CKD [91]. Although HCPs may receive new drug information via reactive educational support from pharmaceutical medical science liaison team members, a comprehensive balanced approach is needed for educating HCPs on treatment options and use of evidence-based combination therapies for reducing CKD progression.

In addition to training, provision of materials such as easy-to-use practice aids to facilitate treatment decisions, specialty society-endorsed clinical care pathways, and treatment algorithms may be of benefit to HCPs. CKD-related educational tools are perceived by primary care clinicians to support CKD management [52], such as implementation of clinical care pathways to assist the management of patients with CKD in primary care [92]. Additionally, accessible practice aids in the form of on-demand smartphone apps have been developed, which include educational resources and tools (e.g., eGFR calculators), that can be utilized to assist practitioners in identifying, evaluating, and managing patients with CKD [93].

Patient Education

We noted previously that limited health literacy in patients is a barrier to good treatment outcomes in CKD and T2DM. The importance of health literacy and patient self-advocacy should not be underestimated because, without it, therapy adherence and persistence is unlikely [94]. The ADA and KDIGO guidelines advocate education for patients so they can work effectively with/alongside HCPs to co-manage their CKD [12]. Care models that emphasize shared responsibility for CKD education among members of the MDT may improve patient outcomes [95]. One study found that patients with advanced CKD who received multidisciplinary pre-dialysis education provided by an MDT including nephrologists, dialysis nurses, pharmacists, dieticians, and social workers had better outcomes, such as reduced unplanned urgent dialysis, CV events, and hospital days, compared with outcomes of patients who did not receive multidisciplinary pre-dialysis education, although no significant survival benefit was found [96]. More recently, a virtual multidisciplinary care program including online education and a virtual MDT consisting of a nurse, pharmacist, social worker, dietician, and patient mentors improved disease knowledge in patients with CKD versus before program initiation [97]. These findings suggest that a multidisciplinary educational approach may be beneficial for patients with CKD, particularly if provided earlier in disease development.

Comprehensive Medication Management Programs: Clinical Pharmacists

Comprehensive medication management is defined as the standard of care that ensures each patient’s medications are individually and regularly assessed to determine whether they are appropriate for the patient (based on other conditions and medications) and effective for the medical condition being treated and that they can be self-administered by the patient as intended [98]. The potential positive impact of a CMM program for patients with CKD associated with T2DM is shown in Fig. 3. There is a need for highly trained individuals, like clinical pharmacists, within the MDT who can focus on medication management while working alongside other HCPs. A collaborative practice agreement (CPA) is a formal agreement between a clinical pharmacist and a licensed prescriber (typically a physician, but may be a nurse practitioner) that allows the prescriber to delegate certain care functions to the clinical pharmacist, which may include initiating, modifying, or discontinuing medications and/or ordering and interpreting laboratory tests [99, 100]. As of 2018, 48 states and the District of Columbia had some form of CPA authority for clinical pharmacists, as allowed by state law [101]. Clinical pharmacists are becoming increasingly recognized for their positive contributions to the MDT in the care of patients with CKD [102]. Indeed, CMM performed by clinical pharmacists may optimize care for patients with CKD and/or T2DM.

Fig. 3.

Fig. 3

Impact of CMM relevant to patients with CKD and T2D. CMM comprehensive medication management

CMM that includes medication reconciliation followed by medication review can lead to the identification of drug-related problems, such as drug–drug interactions [103] and adverse drug reactions [104] (e.g., avoiding drug contraindications or nephrotoxic drugs), as well as drug optimization (including drug dose adjustment and recommending new pharmacotherapy) [105, 106]. As part of this process, clinical pharmacists can assist members of the MDT in patient empowerment/education and patient medication counseling. Such interventions aim to improve treatment adherence, optimize patient outcomes, and prevent further CKD progression. Additionally, clinical pharmacists can facilitate MDT coordination by developing patient monitoring plans and medication management programs for patients with CKD [102]. Furthermore, community pharmacists are well-positioned to identify patients at high risk of developing CKD and recommend/perform point of care testing (e.g., eGFR and UACR) [107].

Comprehensive Medication Management Programs: Disease Outcome Benefits

Use of standard of care plus CMM for patients receiving dialysis is associated with improved medication optimization, lower medication costs, fewer hospitalizations, and shorter hospital stays, versus patients receiving standard of care alone [108]. CMM can result in better patient outcomes. For example, a study in the USA found that after receiving CMM services, the proportion of patients with diabetes achieving all treatment goals (HbA1c < 7%, office blood pressure < 130/80 mmHg, low-density lipoprotein cholesterol < 100 mg/dL, tobacco cessation, and aspirin use) improved from 17.3% to 42.7% (statewide comparison: 8–13%) [109]. In a different observation, average decreases in HbA1c (10–7.7%) and blood pressure (142/83 mmHg to 134/79 mmHg) were reported in patients receiving CMM, which were associated with an estimated 27% reduction in the need for return appointments [110]. Also, patients with diabetes and/or CKD who received CMM services had a greater reduction in mean blood pressure and improved blood pressure control at 9 months compared with those who received usual care [111]. CMM has also been associated with improved medication adherence in patients taking chronic disease medications relevant to CKD, including statins, ACEis or ARBs, and beta-blockers, compared with those who did not receive CMM [112]. Lastly, CMM may be beneficial when coordinating care transitions (e.g., referrals to outpatient services); in an analysis of the impact of CMM on readmission rates using retrospective medical record data, CMM was associated with reductions in hospital readmission rate and risk [113]. Although the analysis performed in that study did not specifically include a CKD population, the concept is still relevant because hospital readmissions for patients with CKD are high [114] and medication therapy problems in care transitions are common in patients with CKD [115].

Newer value-based payment models, such as those developed by the Centers for Medicare & Medicaid Services Innovation Center, incentivize practitioners to provide coordinated, high-quality, and cost-efficient care for Medicare beneficiaries [116]. For example, the Kidney Care Choices (KCC) model provides financial incentives for HCPs in ESKD care organizations to reduce costs and improve the quality of care for patients with advanced CKD and ESKD, with the aim of improving outcomes in these patients [117]. Many value-based kidney care companies are creating their own MDTs that include additional members, such as a care coordinator, nurse, pharmacist, social worker, and dietitian, to work with nephrology practices that typically do not have these types of team members [118]. KCC model metrics include patient activation, measures of depression, optimal dialysis initiation, and total cost of care [119]. These metrics could be positively impacted by specific role functions within the MDT that include a clinical pharmacist who provides CMM, a mental health professional for psychological support, and a care coordinator to improve communication and care between patients and their MDT. A CKD progression metric would give an added incentive for care organizations to include a clinical pharmacist in the MDT to ensure patients are initiated and maintained on guideline-directed therapy to reduce CKD progression risk. Figure 4 gives an overview of how CMM services for patients with CKD associated with T2DM could be implemented.

Fig. 4.

Fig. 4

Proposed process of implementing CMM services for patients with CKD associated with T2DM. CQI continuous quality improvement, ESKD end-stage kidney disease, MTP medication therapy problem, UACR urine albumin-to-creatinine ratio

Conclusion

Chronic kidney disease (and T2DM) is a chronic condition associated with long-term health, financial, and quality-of-life consequences for patients. Barriers to effective care in CKD associated with T2DM include a shortage of specialist clinicians (nephrologists), delays in drug treatment initiation or adjustment, inconsistent screening practices, poor health literacy, costs, and inadequate health insurance coverage. An effective and well-coordinated MDT, especially one that includes a clinical pharmacist as part of a CMM program, will address many of these barriers to effective care. Implementation of a collaborative care MDT approach (incorporating CMM) for CKD associated with T2DM across the USA is recommended.

Acknowledgements

Funding

Medical writing support and the journal’s Rapid Service Fee was funded by Bayer Corporation. The authors did not receive any honoraria for this review.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for this article, take responsibility for the integrity of the work as a whole, and have given their approval of the final draft for the submission.

Medical Writing and Editorial Assistance

Medical writing assistance was provided by Charlotte Maddocks of Envision Pharma Group, funded by Bayer Corporation. Envision Pharma Group’s services complied with international guidelines for Good Publication Practice (GPP4).

Author Contributions

Ellie Kelepouris, Wendy St. Peter, Joshua J. Neumiller, and Eugene E. Wright contributed to writing and reviewing the manuscript and take full responsibility for the integrity of the article content.

Disclosures

Ellie Kelepouris is an advisor for Bayer Pharmaceuticals, CSL-Vifor, AstraZeneca, Boehringer Ingelheim, Akebia, and GSK, and has received royalties from Up to Date. Wendy St. Peter is a consultant for GSK and CSL-Vifor Pharma, and is on the Centers for Medicare and Medicaid Services Technical Expert Panel on Development of a Quality Measure Assessing Delay in Progression of Chronic Kidney Disease (CKD). Joshua J. Neumiller is an advisor for Sanofi, Boehringer Ingelheim, Eli Lilly, and Bayer, and is on the Speakers’ Bureau for Dexcom. Eugene E. Wright is on the Speakers’ Bureau for Abbott Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, and Sanofi; is on the Advisory Boards of Abbott Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, Medtronic, and Sanofi; and is a consultant for Abbott Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly.

Compliance with Ethics Guidelines

This article is based on previously published studies and does not contain any new studies with human participants or animals performed by any of the authors.

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