Proportional, but not absolute, intake of appropriate plant protein is associated with a reduced risk of chronic kidney disease: a cross-sectional study based on NHANES 2005–2018

Introduction

Chronic kidney disease (CKD) is a major global public health challenge, affecting approximately 10% of the world’s population (1). This progressive condition, characterized by the gradual deterioration of renal function, contributes substantially to global morbidity and mortality and imposes a considerable economic burden on healthcare systems (2,3). Despite its impact, knowledge about CKD remains incomplete, as its complex pathophysiological mechanisms and effective prevention strategies are not yet fully understood. The multidimensional burden of CKD, including prevalence, incidence, mortality, and associated healthcare costs, continues to rise, with most pronounced increases observed in low-income countries (4-6).

The pathogenesis of CKD involves complex interactions among genetic susceptibility, environmental exposures, and lifestyle factors (7-9). Among these, dietary patterns are a key modifiable risk factor that plays a pivotal role in both the development and progression of CKD (10,11). Nutritional interventions, due to their cost-effectiveness, patient acceptability, and practical feasibility, have garnered significant attention as a central approach to CKD prevention and management.

Recent epidemiological and clinical studies suggest that plant-based diets may confer protective effects for kidney health (8). While higher plant protein intake has been associated with a reduced risk of CKD (12), completely plant-based dietary patterns may not be appropriate for all individuals. For example, patients with primary hyperoxaluria (13), irritable bowel syndrome (IBS) (14), or plant protein allergies may have limited tolerance for such diets, making this approach controversial. Recent hypotheses indicate that moderate plant-based, low-protein diets may yield additional health benefits for patients with CKD and potentially slow the decline in renal function (15). However, the optimal proportion of plant protein needed to achieve renoprotective effects remains uncertain. Given considerable individual variations in dietary requirements and tolerances, a one-size-fits-all nutritional recommendation is unlikely to be suitable.

This study utilizes data from the National Health and Nutrition Examination Survey (NHANES) to systematically investigate the association between the proportion of plant protein intake and the risk of CKD. Specifically, it aims to identify an optimal range of plant protein consumption that may reduce CKD risk. For populations unable to tolerate high plant protein intake, this research seeks to provide evidence-based recommendations for reasonable plant protein intake levels. The findings will support the development of individualized nutritional guidance to promote kidney health while accounting for individual variability in dietary requirements and tolerances. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-467/rc).

Methods

Study population

The NHANES (https://wwwn.cdc.gov/nchs/nhanes/Default.aspx), conducted by the National Center for Health Statistics, monitors and evaluates health and nutrition patterns across all age groups in the United States. This comprehensive dataset includes demographic details, dietary information, medical examination results, laboratory measurements, survey responses, and restricted-access records. Since 1999, NHANES has been conducted continuously, with results released in 2-year cycles.

This observational study used data from seven NHANES cycles [2005–2018], comprising 70190 participants. Figure 1 presents the participant selection flowchart. We excluded individuals aged <20 years, those who did not complete the first-day dietary assessment at the mobile examination center (MEC), and participants without essential kidney function measures, estimated glomerular filtration rate (eGFR), and albumin-to-creatinine ratio (ACR) data. After applying these criteria, 32,596 participants were included in the final analysis. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Figure 1 Participant screening flow chart. ACR, albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate; FPED, Food Patterns Equivalents Database; NHANES, National Health and Nutrition Examination Survey.

In the latest NHANES study, serum and urinary creatinine levels were analyzed using the Jaffe rate method, and urinary albumin was quantified using a solid-phase fluorescence immunoassay. The eGFR was calculated using the CKD-epidemiology collaboration equation, based on serum creatinine levels (16). The ACR was defined as the urine albumin-to-creatinine ratio (17).

Dietary assessment

Dietary consumption patterns from 2005 to 2018 were analyzed using the first round of 24-h dietary recall interviews. Trained NHANES personnel at the MEC collected this nutritional information directly from participants. Food consumption was assessed using the United States Department of Agriculture (USDA) automated multiple-pass method. NHANES collaborated with the Food Patterns Equivalent Database (FPED), which translates participants’ food and beverage intake into 37 distinct USDA Food Pattern components. The FPED also provided detailed protein intake metrics, including total protein as well as animal- and plant-based sources.

Definitions

CKD was defined as an eGFR below 60 mL/min/1.73 m² or an ACR of 30 mg/g or higher (17).

The FPED categorizes protein-rich foods into plant-based and animal-based sources. Plant proteins include soy products (excluding calcium-fortified soymilk and mature soybeans), nuts, seeds, and legumes such as beans and peas, all recognized as nutrient-dense foods. Animal protein includes various meats (beef, pork, lamb, veal, and game), processed meats (sausages, hot dogs, deli meats, and cured ham), organ meats, poultry (chicken and turkey), and seafood (both high- and low-omega-3 fatty acid varieties), as well as eggs. Total protein intake was calculated as the sum of plant- and animal-based protein sources. The plant-protein ratio was defined as the proportion of protein derived from plant-based foods relative to the total protein consumed.

Covariates

Covariates were collected using a structured questionnaire and included: age (20–34, 35–49, 50–64, or ≥65 years), sex (male or female), race/ethnicity (Mexican American, Non-Hispanic Black, Non-Hispanic White or other), educational attainment (less than high school, high school, or more than high school), family income (income-to-poverty ratio <1, 1–3 or >3), marital status (married/cohabiting, never married, or widowed/divorced/separated), and total calorie intake. Smoking status was classified as former (individuals who have smoked more than 100 cigarettes in their lifetime but currently do not smoke), never (individuals who have smoked fewer than 100 cigarettes in their lifetime), or current (individuals who have smoked more than 100 cigarettes in their lifetime and currently smoke on some days or every day). Alcohol consumption was defined as former (had ≥12 drinks in 1 year and did not drink in the past year, or did not drink in the past year but drank ≥12 drinks in their lifetime), heavy (≥3 drinks/day for women, ≥4 drinks/day for men, or ≥5 binge drinking days per month), moderate (≥2 drinks/day for women, ≥3 drinks/day for men, or ≥2 binge drinking days per month), mild (≤1 drinks/day for women, ≤2 drinks for men), or never (drank <12 drinks in their lifetime) (18). Physical activity levels were categorized as active (≥500 metabolic equivalent (MET) min/week), somewhat active (<500 MET min/week), or inactive (no reported physical activity data) (19). Body mass index (BMI) was calculated using measured height and weight and categorized as <25, 25–30, or >30 kg/m². Diabetes was defined as a self-reported diagnosis of diabetes and/or the use of antidiabetic medication. Hypertension was defined as mean systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, a self-reported diagnosis of hypertension, and/or the use of anti-hypertensive medication. Stroke and cardiovascular disease (CVD) were defined based on self-reported medical history.

Statistical analysis

We incorporated the dietary-day one sample weight (WTDRD1) recommended by NHANES into all analyses. Because NHANES is based on a complex probability sample design, individual sample weights were calculated as 1/7 × WTDRD1 to reflect the seven survey cycles from 2005–2018. Participant characteristics were summarized as means ± standard deviations for normally distributed continuous variables and compared using independent t-tests. Categorical data were presented as frequency counts (percentages) and compared using Chi-squared tests.

The association between dietary plant protein intake and CKD was examined using binary logistic regression. The plant protein ratio, initially analyzed as a continuous variable, was segmented into tertiles for categorical assessment, and P values for trends were calculated. Four distinct models were constructed for comprehensive analysis. The baseline model made no adjustments for potential confounders. Model 1 incorporated demographic and socioeconomic factors, including age, race, sex, education level, income-to-poverty ratio, and marital status. Model 2 further adjusted for lifestyle variables such as BMI, exercise habits, smoking, and alcohol consumption. Model 3, the most comprehensive, additionally controlled for comorbidities like diabetes, hypertension, stroke, and CVD. To examine potential nonlinear associations, restricted cubic spline (RCS) regression was used to assess the relationship between plant protein ratio and CKD risk. The number of knots for the spline function was selected based on a joint assessment of P values and Akaike information criterion (AIC) to achieve an optimal balance between model fit and complexity.

Four sensitivity analyses were performed. First, the outcome measures were modified, using CKD progression risk as the dependent variable in an ordinal logistic regression model (17). CKD progression was evaluated by classifying patients into four risk categories (low, moderately increased, high, and very high) based on eGFR and albuminuria levels. Harrell’s graphical method was used to verify the parallel slope assumption for the ordinal logistic regression model. Second, for subgroup comparisons, participants were divided into two cohorts based on daily protein intake: those consuming >1.5 g/kg/day (high intake group) and those consuming 1.5 g/kg/day or less (nonhigh intake group), with 1.5 g/kg/day serving as the cutoff (20). Third, to ensure the reliability of our findings, we excluded participants with conditions that could bias the findings, including pregnancy, breastfeeding, or active cancer. Fourth, we excluded participants with implausible dietary intake data, defined as men reporting <800 or >4,200 calories per day and women reporting <600 or >3,500 calories daily (21). After applying these exclusions, we constructed the analytical Model.

All analyses were performed using R version 4.2.1, and statistical significance was set at a two-sided P value <0.05.

Results

Baseline characteristics of the study population

The research cohort included 32596 adult participants, all of whom provided comprehensive dietary data on both plant-based and total protein intake. Women represented 51.67% of the cohort, and the majority (67.43%) identified as non-Hispanic White. The mean daily plant protein consumption was 37.35 g (±0.72), accounting for 18.04% (±0.30) of total protein intake. Nearly one in five participants (17.78%) met the diagnostic criteria for CKD, as determined by either eGFR or ACR measurements.

The research participants were stratified into two groups according to CKD status, as outlined in Table 1. Statistical analysis revealed that individuals with CKD had significantly lower plant-based protein intake, total protein intake, calorie consumption, and proportion of plant-derived protein compared with those without CKD (P<0.05).

Plant protein ratio and the incidence of CKD

Elevated dietary plant-sourced protein proportion was associated with a substantial renoprotective effect against CKD in multivariable-adjusted analyses (Table 2). For every 10% increase in plant-sourced protein proportion consumption, there was an estimated 30.2% reduction in CKD risk [adjusted odds ratio (OR) 0.698, 95% confidence interval (CI): 0.571–0.852]. When protein intake was analyzed in tertiles, participants in the highest third of plant protein proportion consumption demonstrated significantly lower odds of developing CKD (OR 0.781, 95% CI: 0.699–0.873) compared with those in the lowest third. The middle tertile showed no statistically significant difference (OR 0.943, 95% CI: 0.812–1.095).

Dose-response relationship between plant protein ratio and CKD

Based on a comprehensive analysis of AIC values and P values, the RCS model with six knots was identified as the optimal choice. This model demonstrated a significant nonlinear relationship (P=0.0005) and achieved the lowest AIC value (18,125.61), indicating the best trade-off between goodness of fit and model complexity. Accordingly, the RCS model with six knots was adopted for subsequent analyses (Table S1). The analysis revealed a curved, rather than linear, relationship between the proportion of plant-based protein in the diet and the risk of developing CKD (Figure 2). The ideal protective ranges for plant-sourced protein proportion were distributed across three distinct intervals: 0.000–4.020%, 11.558–30.151%, and 57.789–100.000%. Each range was associated with a statistically significant reduction in CKD risk.

Figure 2 The RCS model indicated a nonlinear association between plant protein ratio and the risk of CKD. CKD, chronic kidney disease; RCS, restricted cubic spline.

Sensitivity analysis

To validate the findings, multiple sensitivity analyses were conducted. CKD progression was assessed using eGFR and albuminuria measurements, with participants classified into four risk categories: low, moderately increased, high, and very high (17).

Ordinal logistic regression was applied, focusing on CKD progression risk rather than initial disease onset. In the adjusted model, a higher proportion of plant-sourced protein consumption was associated with a lower likelihood of CKD onset (OR 0.660, 95% CI: 0.542–0.802; Table S2). Participants were further stratified into high-protein (daily intake >1.5 g/kg) and nonhigh-protein groups for subgroup analysis. The comprehensive binary logistic regression model yielded statistically significant results. In individuals with nonhigh protein intake, a greater proportion of plant-sourced protein consumption was associated with markedly reduced risk of CKD (OR 0.682, 95% CI: 0.479–0.972, P=0.035). This protective effect was more evident than in those with high-protein intake (OR 0.719, 95% CI: 0.551–0.940, P=0.016; Table S3).

Sensitivity analyses reinforced these conclusions. Excluding pregnant, breastfeeding, or those with a cancer diagnosis did not alter the robustness of the adjusted model (Table S4). Similarly, the exclusion of participants with potentially unreliable dietary data did not weaken the observed inverse relationship between plant-sourced protein proportion consumption and CKD risk (Table S5).

Discussion

The results of this study indicate that a higher proportion of plant-based protein in total daily protein intake is associated with a reduced risk of CKD. This finding highlights a strong inverse relationship between the proportion of plant-sourced protein consumption and the likelihood of renal dysfunction. Further analysis revealed that the association between the proportion of plant protein intake and the risk of CKD was non-linear, and the protective effect was most significant within the appropriate range. Maintaining the proportion of plant protein intake within these intervals may reduce the risk of developing CKD.

These insights pave the way for more adaptable dietary recommendations, proving that adjusting plant protein ratios within a reasonable window can effectively lower CKD risk without sacrificing nutritional variety or practicality. Notably, these kidney-protective effects were more pronounced in individuals with non-high protein overall consumption compared to those consuming higher amounts.

The results of this study provide indirect evidence for the hypothesis proposed by Mocanu et al. (15), suggesting that a dietary pattern rich in plant proteins may exhibit additional renal protective effects in delaying the progression of CKD.

Healthy eating is now deeply ingrained in our collective psyche, with a specific emphasis on warding off and slowing the development of CKD (20). Lately, there has been a steady shift towards a whole-food, plant-forward diet. This diet has caught on like wildfire, thanks to its distinctive perks and the numerous health benefits it offers. As a result, it is receiving more acclaim and popularity than ever before. Researchers have identified several pathways through which plant-based proteins may support kidney health. High blood pressure, excess weight, and type 2 diabetes—all known risk factors for renal impairment—tend to be less prevalent among those consuming plant proteins. Compared to animal-derived proteins, plant-based diets consistently demonstrate advantages, including better blood pressure control, effective weight management, and reduced likelihood of developing type 2 diabetes (22,23). A three-week clinical trial involving 10 healthy participants demonstrated that replacing animal protein with an equivalent amount of plant-based protein led to measurable changes in kidney function. Specifically, researchers observed reduced renal plasma flow, decreased albumin and IgG clearance rates, and increased vascular resistance in the kidneys. These findings suggest that plant proteins may affect renal physiology differently than their animal-derived counterparts (24). The difference in amino acid uptake from plant versus animal proteins could explain their distinct kidney impacts (25,26). People with healthy kidneys produce lower levels of uremic toxins like p-cresyl sulfate and indoxyl sulfate on a plant-heavy diet (27). Research has shown that uremic toxins play a significant role in advancing kidney disease, triggering inflammatory responses, and exacerbating cardiovascular issues (22). Unlike plant-based proteins, animal protein intake disrupts the delicate balance of gut bacteria, encouraging proteolytic fermentation. This process generates higher concentrations of inflammation-inducing compounds, which can impair kidney health and amplify oxidative damage (28,29).

A recent study by Heo et al. (12) utilizing UK Biobank data revealed that increased consumption of plant-based proteins was associated with a lower risk of developing CKD. Nevertheless, it failed to factor in the interplay between plant protein consumption and overall protein intake, a factor that might significantly alter the effects of plant protein on CKD risk. As a result, our research challenges the conventional wisdom of simply touting plant protein intake and instead introduces a more nuanced perspective: the ratio of plant to total protein consumption. The study, through dose-response analysis, identified three distinct protective levels of plant protein intake for the first time, thereby laying down a solid scientific basis for the ideal proportion of plant protein in one’s diet. Furthermore, promoting a diet with an absolute intake quantity of plant-based proteins excessively may not be suitable for every group, particularly those suffering from primary hyperoxaluria (13), IBS (14), and excessive consumption of plant-based proteins may trigger adverse effects, including allergic reactions. However, research remains inconclusive regarding the optimal level of plant protein intake needed to mitigate CKD risk while accounting for overall daily protein consumption. Our findings propose three distinct optimal ranges for plant protein ratios—0.000–4.020%, 11.558–30.151%, and 57.789–100.000%—which effectively reduce CKD risk. These results address a critical gap in current nutritional research on protein intake ratio and kidney health.

Although the application of precise regulation of the daily plant protein intake ratio in clinical practice faces numerous challenges, innovative strategies can be developed by integrating the Internet of Things (IoT) technology in the future. Recent studies have confirmed the potential of IoT in the field of nutritional management of chronic diseases, which can enable real-time diet monitoring and provide personalised feedback (30,31). Incorporating such tools into daily management can not only improve patients’ compliance with the plant protein ratio recommendations proposed in this study but also provide more precise data-driven dietary interventions for high-risk populations, thus holding promise for improving long-term kidney health outcomes.

Limitations

This research has some notable flaws. To start, since NHANES is a cross-sectional study, we cannot establish cause-and-effect relationships. Although our study cannot completely rule out reverse causality, where CKD patients might reduce animal protein intake resulting in increased plant protein proportion, the stability of associations observed through our sensitivity analyses and multiple model adjustments provides robust support for our conclusions. Moreover, the first 24-hour food diary might not accurately depict the typical dietary habits of the subjects. There is also the potential for recall errors, like individuals failing to recall every single morsel consumed or struggling to gauge serving sizes accurately.

Conclusions

This study revealed the synergistic effect between the proportion of plant protein intake and the total daily protein intake in relation to the risk of developing CKD, and for the first time, established three target ranges of daily plant protein intake proportions with significant protective effects. Subgroup analysis indicates that increasing the proportion of plant protein among individuals with nonhigh overall protein intake confers greater renoprotective benefits than among those with higher protein consumption. These findings offer new insights and methodological approaches for examining the relationship between the proportion of dietary plant protein and CKD risk.

Acknowledgments

We gratefully acknowledge the NHANES for providing the open-access database that made this analysis possible.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-467/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-467/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-467/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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