The Impact of Protein Type on Phosphorus Intake, Serum Phosphate Concentrations, and Nutrition Status in Adults with Chronic Kidney Disease: A Critical Review

ABSTRACT

Lower phosphorus intake to prevent hyperphosphatemia for those with chronic kidney disease (CKD) is often recommended. Plant proteins are frequently restricted for their high phosphorus content despite having lower bioavailability. To summarize the evidence on protein type and dietary phosphorus intake, serum phosphate concentrations, and nutritional adequacy in adults with CKD, a search in MEDLINE via Ovid was conducted. Citation lists were reviewed to identify any additional articles. Sixteen articles were included—7 intervention (n = 290) and 9 observational (n = 4933). All intervention trials reported high-plant-protein diets provided adequate protein and adhered to low phosphorus diet guidelines. All intervention trials reported higher plant-protein intake was associated with lower serum phosphate; however, only 2 achieved statistical significance. For observational studies, 2 reported that higher proportions of plant to animal protein resulted in lower phosphorus intake but equivalent serum phosphate concentrations. Two reported that plant protein and animal protein had equivalent correlation values to phosphorus intake and no correlation to serum phosphate concentrations. One trial reported lower total phosphorus and protein intake among those who consumed more plant proteins but did not examine serum concentrations. Four reported lower serum phosphate concentrations among those who consumed more plant proteins but did not report dietary phosphorus intake. Of the observational studies that reported on protein intake, all reported lower protein intake among those with higher versus lower plant-protein intake. BMI tended to be lower among those consuming more plant protein. There was not a consistent relation between protein type and albumin concentrations. Routine restriction of plant-protein foods to prevent hyperphosphatemia in CKD would likely benefit from re-evaluation, as evidence does not suggest that higher plant-protein intake leads to higher serum phosphate concentrations or worse nutritional status, although longer-duration intervention trials with larger sample sizes appear to be warranted.

Statement of significance: Plant protein restriction for management of hyperphosphatemia in chronic kidney disease is ubiquitous, although a summary of evidence supporting this practice does not exist. From this review, evidence suggests that plant proteins are not associated with higher phosphorus intake or serum phosphate concentrations.

Introduction

Hyperphosphatemia is common in chronic kidney disease (CKD) and is associated with worse clinical outcomes (CKD-mineral and bone disorders, cardiovascular events, and mortality) (1). In 2020, the Kidney Disease Outcome Quality Initiative (KDOQI) released clinical practice guidelines for the nutrition care of patients living with CKD (2). In this guideline, it recommends limiting dietary phosphorus intake to maintain normal serum phosphate concentrations (2). This guideline also states that phosphorus source (animal, vegetal protein-based, and additives) be considered but does not provide detailed food lists (2).

The practice of restricting plant proteins, while less frequently restricting animal proteins for phosphorus management, has been well documented (3). That plant proteins take a central role in recommendations to limit phosphorus, while animal proteins do not, is an interesting phenomenon for two reasons. First, animal proteins have higher phosphorus bioavailability than plant proteins (4): plant-based phosphorus bioavailability is often reported to be 20–50%, compared with animal-based phosphorus bioavailability at 40–60% (2). Second, in the general population, increased consumption of plant proteins and reduced consumption of animal proteins is associated with reduced morbidity and mortality (5).

Medical nutrition therapy for patients with kidney disease is complex, as there tends to be multiple dietary modifications necessary (protein, potassium, and sodium, in addition to phosphorus) (6, 7). This creates challenges for creating patient handouts as the phosphorus content of foods needs to be considered within the context of the potassium and protein content of the food item (6, 7). However, that liberalization of plant proteins should be a goal in phosphorus management has been previously recognized (6) and attempts are being made to create new patient teaching materials that focus more on protein-to-phosphorus ratios rather than protein types (1, 6, 7).

Phosphorus tends to be found in high-protein foods (4). In the KDOQI nutrition guideline released in 2000, it was recommended that 50% or more of protein come from high-biological-value sources (8). This recommendation was, in part, aimed at lowering the risk for protein-energy malnutrition, a highly prevalent and potentially fatal complication of CKD (8). The 2020 version now states there is insufficient evidence to recommend animal protein over plant protein, adding that plant proteins may improve lipid profiles and inflammatory markers (2). However, clinicians practicing in this area may be hesitant to change practice if there is concern that it may result in harm to patients. Therefore, practice is not likely to change unless evidence supports that diets high in plant proteins can be nutritionally adequate, without causing hyperphosphatemia. Therefore, to fully explore this topic, both intervention and observational trials were included in this review. Intervention trials providing similar energy and protein levels but modifying the protein type can provide evidence on how protein type impacts phosphorus concentrations and provide a proof of concept that nutrient requirements can be met with different protein types. Observational trials are required to investigate longer-term nutrition outcomes and explore whether or not free-living adults are able to meet nutrition requirements while consuming high amounts of plant proteins.

Given the new 2020 guideline, the aim of this review was to summarize the evidence on the impact of protein type (animal vs. plant) on total dietary phosphorus intake and serum phosphorus concentrations. As a secondary outcome of interest, impacts on nutritional status (measured by albumin and BMI) and dietary intake (protein and energy intake) were also collected. Finally, health outcomes (as reported by the included articles) related to protein type were summarized.

Methods

Study eligibility criteria

This review included studies investigating plant- and animal-protein intake in adults with CKD. Articles needed to include participants with CKD and report on the amount of plant- and animal-protein intake and serum phosphate concentrations and/or total dietary phosphorus intake. Study inclusion criteria were as follows: consideration for protein source (animal vs. protein), CKD population (any stage, including dialysis), and either serum phosphate concentrations and/or dietary phosphorus intake reported. Any type of plant or animal protein, including protein supplements, were included. All study designs were included. Exclusion criteria were kidney transplantation, pediatric population, and animal studies.

Search strategy

A search of the literature was conducted using MEDLINE via Ovid. The search terms included phosphorus, kidney disease, and animal/plant proteins. Fifty-five different search terms were used once all potential synonyms were considered. For the full list of search terms, see Supplemental Table 1. No limits were activated during the search to avoid omission of any relevant publications. The search was completed on 26 September 2020 and re-run on 11 February 2021 (for any potential new articles).

Risk-of-bias assessment

Risk-of-bias assessments were completed using the quality-assessment tools available from the National Heart, Lung, and Blood Institute (9). As all study designs were included in this review the quality-assessment tools available through the National Heart, Lung, and Blood Institute were chosen as they provide a variety of tools, which enabled choosing the correct tool for the study design (9).

For each assessment criteria as stated by the tools, a score of 0 through 3 was awarded. A score of 0 indicated that the answer was either no, not reported, or not applicable, as the case may be. A score of 1 indicated that an answer was available in the article but lacked full details or full adherence to the stated requirements based on the description of the criteria. A score of 2 indicated that some detail was provided but the stated requirements were not fully met, while a score of 3 indicated that all necessary detail was provided and 100% of the requirements were met. Scores were then summed. Summed scores in the first tertile of the total score were considered poor, in the second tertile as fair, and in the third tertile as good.

Results

The initial search yielded 964 articles, in which titles and abstracts were screened for potential inclusion. From the initial screen, 22 full texts were retrieved and reviewed (Figure 1). Fifteen met the inclusion criteria. The citation lists of all included references were then reviewed to identify any additional relevant articles. This yielded 1 additional study for a total of 16 (10–25). In the second search, 971 articles were identified, although no new articles met the inclusion criteria.

FIGURE 1.

Flowchart of article selection.

Studies were published between 1996 and 2020 and were from Africa, Asia, Europe, and North America. Seven studies were intervention trials and 9 were observational. Of the 16, 11 reported on the impact of protein type on phosphorus intake (Table 1). Fifteen reported on the impact of protein type on serum phosphate concentrations. All studies reported albumin and BMI, which were used as surrogate markers of nutritional status for the purposes of this review. A complete summary of reported study findings and objectives is reported in Table 2.

TABLE 1.

Summary of studies¹

Study type	Reference	Country	CKD stage2	Study design	n	Reported outcomes
Intervention	Azadbakht et al., 2009 (13)	Iran	1–2	Crossover—soy supplements provided	100	Diet, serum, nutrition
	Barsotti et al., 1996 (11)	Italy	3b-5	Exact design not clear	62	Diet, serum, nutrition
	Duong et al., 2019 (24)	Taiwan	RRT	Plant- and milk-based supplements provided	53	Diet, serum, nutrition
	Imani et al., 2009 (12)	Iran	RRT	Textured soy protein provided to replace animal protein at 1 meal/d	40	Diet, serum, nutrition
	Moe et al., 2011 (14)	USA	3b	Crossover feeding trial	9	Diet, serum, nutrition
	Moorthi et al., 2014 (17)	USA	3–4	Feeding trial (pre/post analysis)	13	Diet, serum, nutrition
	Sanchis et al., 2019 (21)	Spain	3b	Crossover feeding trial	13	Diet, serum, nutrition
Observational	Chang et al., 2018 (19)	Taiwan	3–5	Cross-sectional comparing omnivores and lacto-ovo vegetarians	100	Serum, nutrition
	Garcia-Torres et al., 2020 (23)	USA	RRT	Cross-sectional (secondary analysis) compared plant-based with animal-based protein	361	Diet, nutrition
	Gebretsadik et al., 2020 (25)	Ethiopia	3–5, includes RRT	Cross-sectional investigated correlations with dietary components	100	Diet, serum, nutrition
	Kandouz et al., 2016 (20)	United Kingdom	RRT	Cross-sectional compared “strict vegetarians” with omnivores	138	Serum, nutrition
	Liu et al., 2020 (22)	China	RRT	Cross-sectional (secondary analysis) comparing protein type with total protein ratio	884	Serum, nutrition
	Ou et al., 2016 (18)	Taiwan	RRT	Case-control—vegetarians with age-matched controls	63	Serum, nutrition
	Scialla et al., 2012 (15)	USA	2–4	Cross-sectional (secondary analysis) comparing protein type with total protein ratio	2938	Diet, serum, nutrition
	Wlodarek et al., 2014 (16)	Poland	4–5	Cross-sectional investigated correlations with dietary components	31	Diet, serum, nutrition
	Wu et al., 2011 (10)	Taiwan	RRT	Cross-sectional compared vegetarians with omnivores	318	Serum, nutrition

¹CKD, chronic kidney disease; RRT, renal replacement therapy including both hemodialysis and peritoneal dialysis.

²CKD stage, Chronic kidney disease stage based on Kidney Disease Outcome Quality Initiative staging using estimated glomerular filtration rate.

TABLE 2.

Summary of included study objectives and reported results in adults living with kidney disease

Study type	Reference	Study objectives	Reported results
Intervention trials	Azadbakht et al., 2009 (13)	To evaluate soy protein on renal markers in patients with diabetic nephropathy	Compared with animal protein, soy consumption reduced urinary urea nitrogen and protein, serum phosphate, and sodium concentrations. Creatinine, urea, calcium, and potassium were not different between groups
	Barsotti et al., 1996 (11)	To investigate the difference between a low-protein vegetarian diet and a traditional low-protein diet in patients with mildly reduced renal function to see if there is a higher risk of hyperkalemia or malnutrition between groups	Compared with a standard low-protein diet, special vegan diets had equivalent urine urea excretion. Special vegan diets had lower urine hydrogen excretion and serum bicarbonate concentrations compared with usual-protein diets. On a special vegan diet, serum phosphorus and potassium were within acceptable limits. There was no impact on serum albumin, triglycerides, or cholesterol and no evidence of malnutrition
	Duong et al., 2019 (24)	To understand if nutrition education and protein supplements improve nutrition status biomarkers in peritoneal dialysis patients; the 3 study arms were nutrition education only, nutrition education with milk-based supplements, and education with soy-based supplements	Nutrition education, either combined or not combined with protein supplements, was associated with increased protein intake and nutritional status (as measured by serum albumin concentrations) but not serum phosphorus in peritoneal dialysis patients with low albumin
	Imani et al., 2009 (12)	The impact of soy on phosphorus and other markers in peritoneal dialysis patients	Soy consumption reduced plasma coagulation factor IX activity, a risk factor for thrombosis
	Moe et al., 2011 (14)	The impact of dietary protein source on phosphorus and hormones	Protein source impacts phosphorus homeostasis. Nutrition education on phosphorus should consider protein source
	Moorthi et al., 2014 (17)	To investigate if diets with 70% plant and 30% animal foods lower urinary phosphorus excretion over a 4-wk period	Diets containing 70% plant protein was safe, well tolerated, and lowered urine phosphorus excretion and may be an alternative to phosphate binders
	Sanchis et al., 2019 (21)	To evaluate the safety of walnuts on phosphorus and other renal-specific markers including cardiovascular risk factors	Daily walnut consumption as part of a sodium, protein, phosphate, potassium-controlled diet did not alter phosphorus, potassium, parathyroid hormone, or fibroblast growth factor 23 concentrations and reduced markers of cardiovascular risk
Observational studies	Chang et al., 2018 (19)	To compare the impact of omnivores and lacto-ovo-vegetarians on nutritional status	Phosphate and triglyceride concentrations were lower among lacto-ovo-vegetarians than omnivores. Both groups consumed protein above the recommendations; no other differences in renal function indices were observed
	Garcia-Torres et al., 2020 (23)	To determine how protein source impacts phosphorus intake	Most patients consumed energy, protein, phosphorus, and potassium below recommendations, but sodium and fats above recommendations. Those consuming more plant proteins had lower phosphorus and protein intakes
	Gebretsadik et al., 2020 (25)	To assess dietary intake against recommendations and total nutrient intake	For most participants, energy, potassium, and phosphorus intake was below recommendations while protein intake was above recommendations. Estimated glomerular filtration rate was positively correlated with animal-protein intake
	Kandouz et al., 2016 (20)	To establish whether higher convective clearances with hemodiafiltration increases middle molecule uremic toxin clearance	Middle molecule uremic toxin clearance was not lower with convective clearances with hemodiafiltration. Middle molecule uremic toxins were negatively correlated with vegetarian diets and residual renal function
	Liu et al., 2020 (22)	To investigate how plant-protein intake impacts cardiovascular mortality in peritoneal dialysis patients (used repeated lab and nutrition measures)	For every 10% increase in time-averaged ratio of plant-based protein to total protein there was an associated reduction for all cause and cardiovascular mortality
	Ou et al., 2016 (18)	To investigate how vegetarian diets impact nutrition and cardiovascular makers in dialysis patients	Compared with omnivores, vegetarians had lower body weights, BMI, serum phosphate, urea, creatinine vitamin D, uric acid, and albumin and normalized protein catabolic rates. Vegetarians had higher brachial-ankle pulse-wave velocity, even after adjustment for confounders
	Scialla et al., 2012 (15)	To evaluate the association of plant-protein intake on risk factors in chronic kidney disease	Those who consumed more plant protein had lower fibroblast growth factor 23 and higher bicarbonate concentrations but not serum phosphate, parathyroid hormone, potassium, albumin, or hemoglobin concentrations
	Wlodarek et al., 2014 (16)	To understand how intake compares to recommendations for adults living with chronic kidney disease	Total, animal, and plant protein was positively correlated with energy and nutrient intake. Estimated glomerular filtration rate was positively correlated with animal-protein intake. Serum phosphate and creatinine were negatively correlated with total and animal-protein intake
	Wu et al., 2011 (10)	To assess the nutritional status of vegetarians on hemodialysis	Compared with omnivores, vegetarians had lower normalized protein catabolic rates, BMI, and midarm circumference and needed more erythropoietin agents to maintain similar hematocrit concentrations. Serum albumin and prealbumin concentrations, muscle strength, subjective global assessment scores, and activities of daily living were not different

Risk-of-bias assessment

Four different quality-assessment tools were used depending on the study design (9). For intervention trials, the “Controlled Intervention Studies" and "Before-After (Pre-Post) Studies with No Control Group” tools were used (9). For observational studies, the “Observational Cohort" and "Cross-Sectional Studies and Case-Control Studies” tools were used (9).

For intervention trials, 2 studies were graded as good [1 randomized intervention trial (21) and 1 before-after analysis study (17)] (Supplemental Tables 2 and 3). The remaining 5 intervention trials were all randomized intervention trials and of these, 4 were graded as fair (12–14, 24) and 1 was graded as poor (11) (Supplemental Table 2). Seven observation trials were graded as fair (10, 16, 18–20, 23, 25), whereas 2 were graded as good (15, 22) (Supplemental Tables 4 and 5). No observational studies were graded as poor.

The impact of plant versus animal protein on phosphorus intake

Eleven articles reported on the impact of protein type and phosphorus intake. Nine articles provided phosphorus intake for both plant-based diets (or vegetarian participants) and animal-based diets (or omnivorous participants) (Figure 2) (11–15, 21, 23, 24). Two studies that did not include specific phosphorus intake amounts (and therefore do not appear in the figure) reported on the correlation of protein type with phosphorus intake. Wlodarek et al. (16) reported no difference between protein type and phosphorus intake (r = 0.586, P < 0.01, vs. r = 0.674, P < 0.01). Gebretsadik et al. (25) reported a higher correlation of animal protein and phosphorus intake versus plant protein and phosphorus intake (r = 0.652, P < 0.01, vs. r = 0.202, P = 0.04).

FIGURE 2.

Daily phosphorus intake by predominant dietary protein type in adults living with chronic kidney disease. Values are means ± SDs unless noted otherwise. No SDs are provided for Sanchis et al. or Barsotti et al. Number of participants: Sanchis, n = 13 (plant and animal); Moe, n = 9 (plant and animal); Moorthi, n = 13 (plant and animal); Imani, n = 18 (plant and animal); Barsotti, n = 15 (plant and animal); Duong, plant n = 20, animal n = 21; Azadbakht, n = 14 (plant and animal); Scialla, plant n = 588, animal n = 587; Garcia-Torres, plant n = 92, animal n = 238. ¹Amount calculated using numbers provided in the article of phosphorus content per mg/kg body weight and a 70-kg person, as cited in the article of the typical subject. As amount calculated, no SDs available. ²Phosphorus consumption as measured during the 24-h observation period of the trial. Meals were provided. Numbers provided are for median and IQRs as opposed to mean and SD. ³Displaying urinary phosphorus excretion comparing a prestudy, unmodified diet with a 70% plant-protein diet. ⁴Animal-protein type labeled as quintile (Q) 1 in the article (lowest plant-protein intake). Plant-protein type labeled as Q5 (highest plant protein intake). Phosphorus amount displayed as mg/1000 kcal per day as presented in the article. *Different between protein-type groups that achieved statistical significance (P < 0.05).

Of the 9 studies displayed in Figure 2, 2 were intervention trials that developed nutritionally equivalent diets comparing protein type (11, 21). Five were intervention trials reporting on the amount of phosphorus consumed when protein type was modified (12–14, 24). Duong et al. (24) reported that those who were given a soy protein supplement consumed a statistically significant lower phosphorus amount than those who were given a milk protein supplement. Moorthi et al. (17) reported on urinary phosphorus excretion (as a surrogate marker of phosphorus intake) in their pre/post study. They reported a statistically significant decrease in urinary phosphorus excretion when diets were switched to 70% ± 0.5% plant protein from 35% ± 0.1% plant protein at baseline (17). Two observational studies reported lower phosphorus intake with increasing plant-protein intake compared with animal protein; these results were statistically significant (15, 23).

Impact of plant versus animal protein on serum phosphate concentrations

Fifteen studies reported on plant- versus animal-protein intake and the impact on serum phosphate concentrations, with 13 specifically providing mean serum phosphate concentrations (Figure 3) (10–15, 17–22, 24). Barsotti et al. (11) reported findings for participants with mild and severe CKD separately; therefore, these results are shown separately in Figure 3. Two additional studies did not report serum phosphate concentrations specifically (and are therefore not shown in the figure) but reported correlation coefficients. Both reported no correlation between plant-protein intake and serum phosphate concentrations [r = −0.0954, P = 0.610 (16), and r = 0.194, P = 0.053 (25)].

FIGURE 3.

Serum phosphate concentrations by predominant dietary protein type among adults with chronic kidney disease. Values are means ± SDs. Number of participants: Azadbakht, n = 14 (plant and animal); Barsotti, n = 15 (plant and animal); Duong, plant n = 20, animal n = 21; Imani, n = 18 (plant and animal); Moe, n = 9 (plant and animal); Moorthi, n = 13 (plant and animal); Sanchis, n = 13 (plant and animal); Chang, plant n = 40, animal n = 60; Kandouz, plant n = 16, animal n = 122; Liu, plant n = 293, animal n = 295; Ou, plant n = 21, animal n = 42; Scialla, plant n = 588, animal n = 587; Wu, plant n = 19, animal n = 299. ¹Animal-protein type labeled as quintile (Q) 1 in the article (lowest plant-protein intake). Plant-protein type labeled as Q5 (highest plant-protein intake). ²Animal-protein type labeled as tertile (T) 1 in the article (highest animal to plant-protein ratio). Plant-protein type labeled as T3 in the article (lowest animal to plant-protein ratio). *Different between protein-type groups that achieved statistical significance (P < 0.05). CKD, chronic kidney disease.

Of those reporting mean serum phosphate concentrations, 7 were intervention trials (11–14, 21). Of the 7 intervention trials, Azadbakht and Esmaillzadeh (13) and Moe et al. (14) reported a statistically significant lower serum phosphate concentration in the plant- versus animal-protein groups despite having diets with similar phosphorus content. The other 5 intervention trials showed no statistically significant difference between serum phosphorus concentrations and protein type (11, 12, 17, 21, 24). Six observational studies reported mean serum phosphate concentrations by protein consumption type. Of these, 4 reported statistically significant lower serum phosphate concentrations among those who self-identify as vegetarians compared with omnivores (10, 18–20). In the remaining 2 studies, a higher versus lower ratio of plant- to animal-protein consumption resulted in no difference in serum phosphate concentrations (15, 22).

Impact of protein type on nutrition outcomes

Twelve articles provided information on nutritional adequacy of the diet specifically (Table 3) (11–16, 18, 19, 21–23, 25). Nine observational studies provided 1 or more clinical markers of nutritional status (10, 15, 16, 18–20, 22, 23, 25). There were 2 intervention trials that were long enough in duration (3–6 mo) to evaluate the impact of protein type on nutritional status (11, 24). All other intervention trials were too short to provide information on how diet modification impacted clinical nutrition-status markers. However, in the 4-week trial by Moorthi et al. (17), a 70% plant-protein diet was not associated with a statistically significant change in hand-grip strength or fat free mass from baseline; however, it was associated with a statistically significant decrease in weight of 0.8 ± 1.3 kg.

TABLE 3.

The impact of protein type on protein intake for intervention and observational studies in adults living with chronic kidney disease¹

Study type	Patient population	Reference	Protein type2	n	Total protein, g/d	Percentage of energy from protein	Protein, g/kg	Meeting protein target based on population3
Intervention trials	Predialysis	Azadbakht et al., 2009 (13)	Plant	14	54 ± 13	94	0.765	Yes
			Animal	14	55 ± 18	94	0.835	Yes
		Barsotti et al., 1996 (11)	Plant	15	Not reported	8	0.70	Yes
			Animal	15	Not reported	7	0.60	Yes
		Moe et al., 2011 (14)	Plant	9	78.9	154	Unable to assess	Unable to assess
			Animal	9	78	14.34	Unable to assess	Unable to assess
		Morthi et al., 2014 (17)6	Plant	13	57.1–98.9	11.9–16.6	0.8–0.91	Yes
		Sanchis et al., 2019 (21)	Plant	13	65.7	13.14	0.80	Yes
			Animal	13	66.1	13.24	0.80	Yes
	Dialysis	Duong et al., 2019 (24)	Plant	20	Not reported	16.6 ± 3.4	1.16 ± 0.32	Yes
			Animal	21	Not reported	17.7 ± 5.7	1.33 ± 0.57	Yes
		Imani et al., 2009 (12)	Plant	18	43 ± 9	16 ± 3	0.7 ± 0.2	No
			Animal	18	40 ± 15	16 ± 7	0.6 ± 0.3	No
Observational studies	Predialysis	Chang et al., 2018 (19)	Plant	40	46.3 ± 14.9*	14.14	0.79 ± 0.22*	Yes
			Animal	60	57.8 ± 15.7	13.94	0.92 ± 0.24	Yes
		Scialla et al., 2012 (15)	Plant	588	Not reported	13 ± 3*	Not reported	Unable to assess
			Animal	587	Not reported	19 ± 4	Not reported	Unable to assess
Observational studies	Dialysis	Liu et al., 2020 (22)	Plant	293	48.7 ± 13.9*	14.84	0.78 ± 0.24*	No
			Animal	295	54.7 ± 13.9	16.14	0.91 ± 0.24	No
		Ou et al., 2016 (18)	Plant	21	47.29 ± 15.42*	13.14	0.945	No
			Animal	42	60.57 ± 21.88	14.54	1.085	Yes

¹*Significant, with P ≤ 0.05 when comparing plant with animal-protein intake.

²Protein type: “plant” refers to predominantly plant or vegetarian-type diet; “animal” refers to omnivorous or control diet.

³Protein target for predialysis: 0.6–0.8 g/kg; protein target for dialysis: 1.0–1.2 g/kg.

⁴Calculated using information provided in the article using the Atwater coefficient of 4 kcal/g of protein. Formula used: (grams per day protein intake × 4) ÷ total reported energy intake.

⁵Calculated using the formula: grams per day protein intake ÷ kilograms of body weight.

⁶Moorthi et al. was a pre/post study and did not provide specific information regarding the prestudy “free-living” diet of participants.

With regard to nutritional adequacy of diets, 5 interventions trials demonstrated that, regardless of the primary protein type, equivalent protein and phosphorus diets could be designed to meet the protein requirements for the predialysis population (11, 13, 14, 21). Imani et al. (12) investigated the impact of switching 60 g of animal protein/d with 28 g of textured soy flour in patients on peritoneal dialysis and reported that both the control group (no supplements) and the soy supplement group did not meet protein requirements. All observational studies reported that increased plant-protein intake was associated with a statistically significant lower total protein intake (15, 18, 19, 22). As protein recommendations for adults living with CKD are based on grams of protein intake per kilogram of body weight, this was also considered. Three observational studies either provided this information or sufficient information such that it could be calculated. In the predialysis population, 1 study reported that grams of protein intake to kilogram of body weight met recommendations (19). In the dialysis population, 2 studies reported that those who consumed more plant protein did not meet the grams per kilogram protein target (18, 22), although in one of these studies, omnivores were also below target (22). Three articles did not provide protein intake amounts but reported the correlation between protein type and total protein intake (16, 23, 25). One article suggested a similar correlation between total protein intake and plant protein compared with total protein and animal protein (r = 0.627, P < 0.01, vs. r = 0.574, P < 0.01) (25), whereas the other 2 articles reported a stronger correlation between animal protein to total protein than plant protein to total protein [r = 0.8997, P < 0.01, vs. r = 0.5243, P = 0.002 (16), and 0.761 vs. 0.439, both P < 0.01 (23)].

With regard to clinical markers of nutritional status and protein type, there was no clear association between protein type and serum albumin concentrations (Table 4). Only 2 studies reported statistically significant differences. One study reported higher albumin concentrations among those who consumed more plant protein (22), while the other reported higher albumin concentrations among those who consumed more animal protein (18).

TABLE 4.

Protein type and markers of nutritional status in adults living with kidney disease

Study type	Patient population	Reference	Protein type1	n	Albumin, g/dL	P	BMI, kg/m2	P	Other nutrition status markers provided by article
Intervention trials	Predialysis	Barsotti et al., 1996 (11)	Plant	15	4.1 ± 0.5	Not reported	Not reported	Not applicable	Authors reported weight stable during intervention. No evidence of malnutrition
			Animal	15	4.0 ± 0.5		Not reported
	Dialysis	Duong et al., 2019 (24)	Plant	20	3.3 ± 0.4	≥0.05	Not reported	Not applicable	Total protein (mg/dL), 6.7 ± 0.72
			Animal	21	3.4 ± 0.3		Not reported		Total protein (mg/dL), 7.0 ± 0.72
Observational studies	Predialysis	Chang et al., 2018 (19)	Plant	40	4.01 ± 0.44	0.662	23.3 ± 3.5	0.039	None reported
			Animal	60	3.97 ± 0.43		24.9 ± 3.7
		Scialla et al., 2012 (15)3	Plant	588	Not reported	0.2	30.0 ± 7.3	<0.001	None reported
			Animal	587			33.2 ± 8.0
	Dialysis	Garcia-Torres et al., 2020 (23)	Plant	92	3.37 ± 0.45	0.585	Not reported	Not applicable	Prealbumin (mg/dL), 30.04 ± 8.862
			Animal	238	3.52 ± 0.47		Not reported		Prealbumin (mg/dL), 32.18 ± 9.582
		Kandouz et al., 2016 (20)	Plant	16	3.87 ± 0.35	0.53	25.4 ± 5.2	0.5	Lower muscle mass but not fat mass
			Animal	138	3.94 ± 0.43		26.5 ± 6.0		Higher muscle mass
		Liu et al., 2020 (22)5	Plant	293	3.56 ± 0.49	<0.05	23.4 ± 3.6	>0.05	Severe malnutrition, n = 5 (3.5%)6
			Animal	295	3.48 ± 0.44		23.0 ± 3.7		Severe malnutrition, n = 4 (3.6%)6
		Ou et al., 2016 (18)	Plant	21	3.77 ± 0.35	0.009	20.39 ± 2.14	0.013	nPCR4 (g/kg per day), 1.02 ± 0.272
			Animal	42	4.02 ± 0.35		22.46 ± 3.38		nPCR4 (g/kg per day), 1.24 ± 0.362
		Wu et al., 2011 (10)	Plant	19	3.76 ± 0.08	≥0.05	20.2 ± 0.8	Not reported	Prealbumin (mg/dL), 29.7 ± 1.82 nPCR4 (g/kg per day), 1.10 ± 0297
			Animal	299	3.92 ± 0.03		22.7 ± 0.3		Prealbumin (mg/dL), 33.1 ± 2.52 nPCR4 (g/kg per day), 1.20 ± 0247

¹Protein type: “plant” refers to predominantly plant or vegetarian-type diet’ “animal” refers to omnivorous or control diet.

²Reported P value comparing plant- with animal-protein type, not significant with P ≥ 0.05

³Plant-type protein values reported as quintile 5 in the article, representing highest plant-protein intake. Animal-type protein values reported as quintile 1 in the article, representing lowest plant-protein intake.

⁴nPCR (normalized protein catabolic rate) can be used in dialysis patients to assess protein intake. A lower nPCR can be indicative of less protein intake between dialysis sessions.

⁵Plant-type protein values reported as tertile 3 in the article for highest ratio of plant protein to total protein; Animal-type protein values reported as tertile 1 in the article for lowest ratio of plant protein to total protein.

⁶Severe malnutrition: as reported by the article, how this was diagnosed is not reported.

⁷Reported P value comparing plant- with animal-protein type, significant with P < 0.05.

Discussion

In this review, we set out to examine the impact of protein type on phosphorus intake, serum phosphate concentrations, and nutritional status. This review is particularly relevant as the 2020 KDOQI guidelines have changed their statement on protein type for this population (2). In 2000, high-biological-value protein was encouraged to make up at least 50% of protein in this population (8), whereas the 2020 guidelines no longer make this stipulation. Phosphorus is found in protein foods (1), which may also contain potassium (6, 7). Given the multiple nutrition interventions required in the CKD population, how to best operationalize a dietary phosphorus restriction is particularly nuanced (6, 7).

In this review, we considered both total phosphorus intake and serum phosphate concentrations. The consideration of both phosphorus intake and serum concentrations together helps in understanding how each of these variables may impact the other. For example, if plant proteins were consistently associated with higher serum concentrations, one might hypothesize that this was related to increased phosphorus intake from these “high” phosphorus foods. However, the articles in this review generally agreed that higher amounts of plant compared with animal-protein intake were not associated with either higher phosphorus intakes or serum concentrations. That both Barsotti et al (11) and Sanchis et al (21) demonstrated that serum concentrations were not higher with higher plant-protein intake is likely related to differences in the bioavailability of these foods. The bioavailability of phosphorus in plant foods has been demonstrated to be lower than the bioavailability of phosphorus from animal foods (1). Phosphorus in plant foods tends to be phytate bound, which makes it less bioavailable compared with phosphorus in animal foods, which tends to be bound to digestible components such as proteins or phospholipids (26). Lower bioavailability from plant foods would explain why increasing intakes of phosphorus from plant sources does not necessarily correlate to higher serum phosphate concentrations.

In addition to understanding the relationship between phosphorus intake and phosphate concentrations is consideration for how varying protein type may impact nutritional status and outcomes. Both intervention and observational trials were included in this review. We included intervention trials that were designed to have comparable amounts of phosphorus while modifying protein type to ensure that diets could be designed to both provide adequate protein from plant sources while adhering to low-phosphorus guidelines. The diet designs of the intervention trials confirmed that diets made up of plant protein can both meet nutrition requirements and stay within dietary restrictions for predialysis patients; however, for patients receiving dialysis, in whom protein requirements are higher, this was less clear and remains an area for future study.

One limitation of intervention trials is that they cannot answer if free-living individuals with CKD have the capacity or resources to design their own diets with adequate protein if animal sources are not encouraged. In this regard, observational trials are useful. In this review, observational studies reported lower total protein intakes in either their vegetarian or higher plant-protein intake groups, compared with the omnivore or higher animal-protein intake groups, with all of these results achieving statistical significance, although whether or not this translates to poorer nutritional status is not clear as studies did not consistently demonstrate a clear link between albumin concentrations and protein type. However, albumin as a surrogate marker for nutritional status has limitations and it is encouraged to consider other nutrition markers in conjunction with serum albumin concentrations (2).

With regard to body weight, most trials reported lower BMI among those who consumed more plant protein than animal protein. However, whether or not this is a concern for malnutrition is not clear as, in all cases, BMIs were within or above the ideal normal accepted weight ranges for BMI. BMI (in kg/m²) in the underweight category (<18.5) is associated with higher risks for mortality for the dialysis population and potentially in the predialysis population; however, it is noted that BMI alone cannot diagnose protein-energy wasting, unless BMI is very low (<18) (2). Further studies that use a variety of tools to assess the impacts of protein type on nutritional status and body composition, including subjective global assessments or malnutrition inflammation scores, normalized protein catabolic rates, or even DXA (2), appear to be warranted.

One strength of this review was the diversity of CKD stages, including 6 studies (10, 12, 18, 20, 22, 24) investigating participants receiving renal replacement therapy (either hemodialysis or peritoneal dialysis). Renal replacement therapy significantly increases the risk of hyperphosphatemia and the resulting negative health outcomes (27). In our review, we found that, even in those receiving renal replacement therapy, higher plant-protein intake was not associated with higher serum phosphate concentrations. This suggests that protein type for phosphorus management may not be dependent on CKD stage.

Specific to the observational studies, a noted strength was that most studies used validated tools to assess dietary intake (including 3- and 7-d food records and food-frequency questionnaires) (10, 15, 16, 22, 23, 25). The use of validated diet tools to assess dietary intake is important as it increases the reliability of the results. In addition, most observational studies also considered different amounts of plant-protein intake in their analysis and used valid outcome assessment markers multiple times.

One limitation noted with regard to the intervention trials included in this review is that 3 studies investigated the impact of plant-protein supplements. The concern with this is that plant-protein supplements may not be generalizable to all plant-protein foods. Specifically, Azadbakht and Esmaillzadeh (13), Duong et al. (24), and Imani et al. (12) analyzed the impact of replacing animal protein at a meal with soy protein supplements on serum phosphate concentrations. All of these studies reported lower serum phosphorus concentrations with soy protein compared with standard omnivorous diets and may make these results less generalizable. However, in the case of Imani et al. (12), the soy supplement was provided as textured soy protein. This supplement was given with a recipe for preparation and it was used to replace 1 animal protein choice at 1 meal per day. The design of this study is relevant as it allows us to understand how the food matrix may impact outcomes (phosphorus intake and serum concentrations) with substitution of 1 plant-protein choice for 1 animal-protein choice.

Another limitation noted in this review was the baseline serum phosphorus concentration. All studies reported mean serum phosphate concentrations between 0.94 and 1.78 mmol/L, which predominantly falls within ideal serum phosphate ranges for this population (1.16–1.68 mmol/L) (28). For those experiencing hyperphosphatemia, it is unclear from these results if changing 1 protein source for the other would result in normalized serum phosphate concentrations. However, it may suggest that if patients are experiencing hyperphosphatemia that protein type (animal vs. plant) may not be the cause. This was previously demonstrated by Byrne et al. (29) in their pilot study that examined the impact of changing 2 animal-protein sources for plant-protein sources per day in 74 adults with hyperphosphatemia receiving hemodialysis. In this study, the authors reported that dietary modification did not significantly impact serum phosphorus or potassium concentrations (29). This highlights that additional intervention trials looking at substituting protein type for the management of hyperphosphatemia are warranted.

Another limitation is that confounders that impact nutritional status and serum phosphate concentrations were not extensively examined. Nutritional status can be impacted by several factors, including, but not limited to, frailty, comorbidities, and dialysis adequacy (30). Long-term intervention trials that can control for these confounders are likely required to fully understand the impact of protein type on nutritional status and outcomes such as hyperphosphatemia. With regard to serum phosphate concentrations, it is well known that these concentrations can fluctuate and will also be influenced by several factors, including, but not limited to, diurnal variation, dietary intake, dialysis adequacy, and phosphate binders (31). Ideally, studies using both repeated dietary measures and repeated laboratory measures would be best suited to understand both fluctuations in dietary intake and serum phosphate concentrations.

Another limitation in this review was that at least 1 notable work that we are aware of (29) was not captured by our search strategy. In our search strategy, we used 3 key terms to identify articles, which included kidney disease, phosphorus, and protein. The keywords for the missed article included renal and phosphorus but not protein. This may suggest that a search strategy using only renal and phosphorus as key terms may identify additional articles relevant to this topic, although would lack the specificity of our search strategy. A further limitation relates to publication bias. It has been reported that articles that find statistical significance are more likely to be published (32). In this area, where the goal for many researchers is likely to prove equivalency between protein types, by design, the results may not achieve statistical significance and may therefore be harder to publish.

One area of concern in the included studies is related to sample size. For the intervention studies, several had relatively small sample sizes and were described as pilot studies. There is some potential that the statistical nonsignificance of the results was related to being underpowered to determine differences in our outcomes of interest. Well-powered intervention trials are therefore warranted to determine the impact of protein type on phosphate concentrations and nutritional status. For the observational studies, it was noted that 3 studies had large differences in group sizes between vegetarians and omnivores (10, 19, 20). Forty percent of Chang et al.’s (19) sample was vegetarian; however, in the case of Kandouz et al. (20) and Wu et al. (10), only 11% and 6% of the sample, respectively, were considered vegetarian. As the vegetarians in these cohorts made up a small percentage of the total participants, it is possible that those who followed vegetarian diets may have shared other traits that made them different from the general sample population (such as socioeconomic status, cultural or religious background) introducing potential confounders into the analysis. Ou et al. (18) used a more robust design for comparing vegetarians with nonvegetarians by using a case-control design and reported the same results as the other articles (10, 19, 20), strengthening our ability to have confidence in their results. However, as these were observational studies, no cause-and-effect relation can be established.

In conclusion, in this critical literature review examining the impact of protein type (animal vs. plant) on total phosphorus intake in CKD we found that both plant- and animal-protein sources were compatible with the restricted phosphorus diet recommendations. With regard to serum phosphate concentrations, those consuming higher amounts of plant protein tended to have either equivalent or lower serum phosphate concentrations than those consuming higher amounts of animal protein. However, as serum concentrations reported in these studies tended to be within the ideal ranges, it is not clear if changing protein source (i.e., from plant to animal) would improve hyperphosphatemia in the CKD population. Furthermore, while intervention trials have demonstrated a proof of concept that adequate protein intakes can be achieved with well-planned high-plant-protein diets, observational data suggest that higher plant-protein intakes tend to be associated with lower energy and protein intake, which may increase the risk of malnutrition. More evidence to confirm that high-plant-protein diets are nutritionally adequate, especially in the dialysis population, are needed.

Notes

KP is supported by a scholarship from the Canadian Institute of Health Research (CIHR) and Kidney Foundation of Canada. Outside of this work, CR also reports grants from CIHR, the Natural Sciences and Engineering Research Council of Canada , and several other agencies. DRM is currently funded by the CIHR, Kidney Foundation of Canada, and several other agencies.

Author disclosures: The authors report no conflicts of interest.

Supplemental Tables 1–5 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/advances/.