Adherence to Plant-Based Diets and Risk of CKD Progression and All-Cause Mortality: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Saira Amir; Hyunju Kim; Emily A Hu; Ana C Ricardo; Katherine T Mills; Jiang He; Michael J Fischer; Nishigandha Pradhan; Thida C Tan; Sankar D Navaneethan; Mirela Dobre; Cheryl AM Anderson; Lawrence J Appel; Casey M Rebholz

doi:10.1053/j.ajkd.2023.09.020

. Author manuscript; available in PMC: 2025 May 1.

Published in final edited form as: Am J Kidney Dis. 2023 Dec 14;83(5):624–635. doi: 10.1053/j.ajkd.2023.09.020

Adherence to Plant-Based Diets and Risk of CKD Progression and All-Cause Mortality: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Saira Amir ^1,^2,^#, Hyunju Kim ^2,^3,^#, Emily A Hu ⁴, Ana C Ricardo ⁵, Katherine T Mills ⁶, Jiang He ⁶, Michael J Fischer ⁵, Nishigandha Pradhan ⁷, Thida C Tan ⁸, Sankar D Navaneethan ⁹, Mirela Dobre ⁷, Cheryl AM Anderson ¹⁰, Lawrence J Appel ^2,³, Casey M Rebholz ^2,³, CRIC study investigators

¹Department of Medicine, UNC Health Southeastern, Lumberton, North Carolina, USA

²Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA

³Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

⁴Foodsmart, San Francisco, California, USA

⁵Division of Nephrology, Department of Medicine, University of Illinois, Chicago, Illinois, USA

⁶Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA

⁷Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA

⁸Division of Research, Kaiser Permanente Northern California, Oakland, California, USA

⁹Baylor College of Medicine, Houston, Texas, USA

¹⁰The Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, California, USA

SA and HK contributed equally to this work.

CRIC Study Investigators: Jing Chen, MD, MMSc, MSc, Debbie L. Cohen, MD, Harold I. Feldman, MD, MSCE, Alan S. Go, MD, James P. Lash, MD, Robert G. Nelson, MD, PhD, MS, Mahboob Rahman, MD, Panduranga S. Rao, MD, Vallabh O. Shah, PhD, MS, and Mark L. Unruh, MD, MS.

Authors’ Contributions: Research idea and study design: CMR; data acquisition: CMR; data analysis/interpretation: SA, HK, EAJ, ACR, KTM, JH, MJF, NP, EH, TCT, SDN, MD, CAMA, LJA; statistical analysis: SA, HK; supervision or mentorship: HK, CMR. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate.

^✉

Corresponding author: Dr. Casey M. Rebholz, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Suite 2-500, Baltimore, Maryland 21287, crebhol1@jhu.edu

PMCID: PMC11034716 NIHMSID: NIHMS1947337 PMID: 38103719

Abstract

Rationale & Objective:

Studies have shown that generally healthy individuals who consume diets rich in plant foods have a lower risk of incident chronic kidney disease (CKD) and cardiovascular disease. This study investigated the prospective associations of plant-based diets with the risk of CKD progression and all-cause mortality in patients with CKD.

Study Design:

Prospective cohort study.

Setting & Participants:

2,539 participants with CKD recruited between 2003 – 2008 into the Chronic Renal Insufficiency Cohort (CRIC) study.

Exposures:

Responses on the Diet History Questionnaire were used to calculate scores for the overall plant-based diet index, healthy plant-based diet index, and unhealthy plant-based diet index.

Outcomes:

(1) CKD progression defined as ≥50% estimated glomerular filtration rate decline from baseline or kidney replacement therapy (dialysis, transplant), (2) all-cause mortality.

Analytical Approach:

Cox proportional hazards models to compute hazard ratios (HR) and 95% confidence intervals (95% CI) adjusting for lifestyle, socioeconomic, and clinical covariates.

Results:

There were 977 CKD progression events and 836 deaths during a median follow-up period of 7 and 12 years, respectively. Participants with the highest vs. lowest adherence to overall plant-based diets and healthy plant-based diets had 26% (HR: 0.74, 95% CI: 0.62, 0.88, p-trend<0.001) and 21% (HR: 0.79, 95% CI: 0.66, 0.95, p-trend=0.03) lower risks of all-cause mortality, respectively. Each 10-point higher score of unhealthy plant-based diets was modestly associated with a higher risk of CKD progression (HR: 1.14, 95% CI: 1.03, 1.25) and all-cause mortality (HR: 1.11, 95% CI: 1.00 to 1.23).

Limitations:

Self-reported diet may be subject to measurement error.

Conclusions:

Adherence to an overall plant-based diet and a healthy plant-based diet is associated with a reduced risk of all-cause mortality among individuals with CKD. An unhealthy plant-based was associated with an elevated risk of CKD progression and all-cause mortality.

Keywords: chronic kidney disease, death, dietary intake, end-stage renal disease, plant-based diet, plant-based protein, morbidity/mortality

Plain Language Summary

Plant-based diets are healthful dietary patterns that have been linked to lower risk of chronic diseases. However, the impact of plant-based diets on clinical outcomes in patients with chronic kidney disease (CKD) is not well established. In 2,539 individuals with CKD, we examined the associations of adherence to 3 different types of plant-based diets with the risks of CKD progression and all-cause mortality. We found that following an overall plant-based diet and a healthy plant-based diet was associated with a lower risk of all-cause mortality. In contrast, following an unhealthy plant-based diet was associated with a higher risk of CKD progression and all-cause mortality. These results suggest that the quality of plant-based diets may be important for CKD management.

INTRODUCTION

Nutritional factors play an important role in the development of chronic kidney disease (CKD) and its progression, and certain dietary modifications may have a favorable impact on important clinical outcomes.¹ Prior studies in individuals with CKD have primarily focused on individual nutritional factors (total protein, potassium, phosphorus intake)rather than a holistic diet.¹ Though these nutrient-based guidelines are important to consider, an overall diet, which takes into account synergism of foods and nutrients, may be easier to understand and implement.²

To date, few studies examined the association between dietary patterns and clinical outcomes in the setting of CKD.³ We have previously reported that higher vs. lower adherence to healthy dietary patterns (Alternative Healthy Eating Index-2010, alternate Mediterranean diet, and the Dietary Approaches to Stop Hypertension (DASH) diet) was consistently associated with a lower risk of CKD progression and all-cause mortality in a large cohort of individuals with CKD.⁴

The Kidney Disease Outcomes Quality Initiative (KDOQI) guideline for nutrition in CKD recommends evaluating the association between dietary patterns with clinical outcomes (CKD progression and cardiovascular disease ) in prospective studies with sufficient duration of follow-up.⁵ Plant-based diets (high in plant foods and low in animal foods) are healthful dietary patterns that have been linked to lower risk of incident diabetes, hypertension, and cardiovascular idsease.^6–10 A recent study conducted in a general population observed that individuals who consume a diet high in healthy plant foods and low in animal foods had a lower risk of incident CKD and slower decline in estimated glomerular filtration rate (eGFR).¹¹ However, the impact of plant-based diets on clinical outcomes in patients with CKD is not well established.¹²

To address this gap, the aim of our study was to investigate the associations of plant-based diets with CKD progression and all-cause mortality in a cohort of individuals with reduced kidney function, i.e., the Chronic Renal Insufficiency Cohort (CRIC) study.

METHODS

Study Population

The CRIC study is a multicenter prospective cohort study which recruited a racially and ethnically diverse group of adults aged 21 to 74 years with mild to moderate CKD (eGFR of 20 to 70 mL/min per 1.73 m²) between 2003 to 2008.^13,14 Participants were considered ineligible if they received a prior diagnosis of polycystic kidney disease, were on active immunosuppression for glomerulonephritis, or had a serious chronic illness. Further exclusion criteria included participants who were institutionalized (e.g., prisoner, nursing home or skilled nursing facility resident), were unable or unwilling to give consent, and those who were unlikely or unable to participate in the study procedures. Participants attended annual in person visits and completed a telephone interview every six months to provide information on study outcomes and updates on general health and contact information. Participants provided informed consent, the study protocol was approved by institutional review boards at participating institutions, and research was conducted in accordance with ethical principles.

From 3,939 eligible participants, we excluded participants with missing data from the diet history questionnaire at baseline visit (Figure S1). Participants were also excluded if they reported implausible energy intake, defined as <500 or >3,500 kcal/d in women and <700 or >4,500 kcal/d in men. Further exclusion criteria included participants who were missing data on covariates, missing data required to calculate diet scores, and those with missing information for the outcome or follow-up time. A total of 2,539 participants remained for this analysis.

Plant-Based Diet Scores

Dietary intake was assessed using the National Cancer Institute Diet History Questionnaire (DHQ) at the baseline visit. The DHQ assesses frequency of intake of 124 food items.^4,15 We assessed adherence to plant-based diets using established diet indices for an overall plant-based diet score, a healthy plant-based diet score, and an unhealthy plant-based diet score (Table S1).^8,16 Foods and beverages were categorized into 17 food groups. These 17 food groups were then categorized into broader categories (healthy plant foods, unhealthy plant foods and animal foods). Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, and tea/coffee. Unhealthy plant foods included fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets and desserts. Animal foods included animal fats, dairy, eggs, fish/seafood, meat (poultry and red meat), and miscellaneous animal foods. After classifying foods into appropriate food groups, we calculated energy-adjusted consumption of each food group using the residual method.¹⁷ Intake of each food group was regressed on total energy intake to derive residuals of each food group (calculated as observed intake minus predicted intake). Residuals, which are independent of total energy intake, were used to rank participants into quintiles.¹⁷

For the overall plant-based diet index, higher intake of all plant foods was positively scored. For instance, those in the highest quintile of whole grain consumption received a score of 5 and those in the lowest quintile received a score of 1. For the healthy plant-based diet index, higher intake of only healthy plant foods received higher scores. For the unhealthy plant-based diet index, higher intake of only unhealthful plant foods received higher scores. For all plant-based diet indices, higher intake of animal foods received lower scores (negatively scored). For example, those in the highest quintile of animal fat consumption received a score of 1 whereas those in the lowest quintile received a score of 5. Plant-based diet scores were divided into tertiles for analysis, with the third tertile representing the highest level of adherence and the first tertile representing the lowest level of adherence. The tertiles have unequal numbers because there there were participants with the same plant-based diet scores.

Outcome Ascertainment

The primary outcome for our study was CKD progression defined as ≥50% decline in eGFR from the baseline visit or renal replacement therapy (dialysis or kidney transplant). Ascertainment of renal replacement therapy was conducted through follow-up visits, telephone interviews, and linkage with the U.S. Renal Data System registry. Additional information was obtained through hospital chart reviews and confirmed by dialysis units.

The secondary outcome of all-cause mortality was ascertained from interviews with next of kin, hospital chart review, death certificates, and linkage with the Social Security Death Master File.

CRIC participants were followed, for both CKD progression and all-cause mortality, until the end of 2018 (over a maximum period of 14.6 years), and they were censored at the time of withdrawal of informed consent, loss to follow-up, end of follow-up, or death. The observed longer median follow-up time for all-cause mortality relative to CKD progression is attributed to the fact that participants live with CKD (and other health conditions) for a period of time before experiencing death.

Assessment of Covariates

Sociodemographic characteristics (age, sex, race, education, income), lifestyle behaviors (smoking status, alcohol consumption, physical activity), medical history, current medication use, and height and weight measurements to calculate body mass index (BMI) were obtained at the baseline visit. eGFR (mL/min/1.73 m²) was estimated using a CRIC-specific equation that includes age, sex, race, cystatin C, and serum creatinine, along with 24-hour urine protein (g/24h) measurements.¹⁸ Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or self-reported use of antihypertensive medications. Diabetes was defined as fasting glucose measurement of ≥126 mg/dL, random glucose measurement of ≥200 mg/dL, or self-reported use of insulin or antidiabetic medication. History of any cardiovascular disease was self-reported by participants.

Statistical Analysis

Participant and nutritional characteristics were reported using descriptive statistics and compared according to tertiles of plant-based diet indices using analysis of variance (ANOVA) for continuous variables and chi-square tests for categorical variables.

We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the prospective association between plant-based diet indices and time to CKD progression and all-cause mortality. Model 1 was adjusted for clinical sites (seven sites), sex (men, women), race (non-Hispanic white, non-Hispanic black, Hispanic and others), education (less than high school, high school graduate, some college, and college graduate or higher), age (continuous), income (categorical), total energy intake (continuous), and physical activity (continuous variables), smoking status (yes/no), and alcohol use (yes/no). Model 2 was adjusted for all covariates in model 1 plus obesity status defined as BMI ≥ 30 kg/m², eGFR and 24-hour urinary protein as continuous variables, diabetes (yes/no), hypertension (yes/no), history of cardiovascular disease (yes/no), and use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (yes/no). HRs were calculated according to tertiles using tertile 1 as the reference group, representing lowest adherence to plant-based diets, and per 10-point higher plant-based diet score. We tested for linear trend across tertiles by using the median value within each tertile of the diet index. We explored the shape of the association between the overall plant-based diet index and all-cause mortality using two linear spline terms with a knot at the reference point (10^th percentile of the overall plant-based diet index, i.e., 43) in model 2. We placed the reference point at the 10^th percentile, because the shape of the association was identical for the 5^th, 10^th, 15^th, or 20^th percentiles.

As a sensitivity analysis, in fully adjusted models, we 1) tested for interaction between plant-based diets and education (less than high school, high school, some college, college graduate or higher), and plant-based diets and income (≤$50,000, >$50,000) to assess if low adherence to plant-based diets is a marker of socioeconomic status, 2) used renal replacement therapy (dialysis or kidney transplantation, n=741) as the outcome, excluding eGFR decline, 3) adjusted BMI as a continuous variable, 4) modeled 3 food categories (healthy plant foods, unhealthy plant foods, and animal foods) and 5) 17 food groups within plant-based diets indices simultaneously to assess if a particular food category or food group is related to kidney health, and 6) investigated if fiber intake or dietary acid load was associated with CKD progression and all-cause mortality. As a post-hoc analysis, we examined the association between plant-based diets and incident cardiovascular disease to assess if reduction of the risk of all-cause mortality was related to incident cardiovascular disease. We conducted subgroup analyses by individuals with comorbidities at baseline (diabetes vs. no diabetes, hypertension vs. no hypertension, history of cardiovascular disease vs. no history of cardiovascular disease).

We compared the characteristics of the participants who were excluded vs. included for the analyses. Compared to the participants who were included for analyses, those who were excluded were more likely to be men, Hispanic, have less than a high school education, have income <$20,000, be a current smoker, have diabetes, have hypertension, have history of cardiovascular disease, and have higher 24-hour urine protein. Age, BMI, eGFR, medication use, and plant-based diet scores were similar for those excluded vs. included.

The analysis was conducted using Stata statistical software, version 16 (StataCorp LLC, College Station, Texas).

RESULTS

Participant and Nutritional Characteristics

The overall plant-based diet index had scores ranging from 30 to 73, the healthy plant-based diet index had scores ranging from 31 to 75, and the unhealthy plant-based diet index had scores ranging from 29 to 76. Participants in the highest tertile of overall plant-based diet group were more likely to be older and women; were less likely to be obese, current smokers, and current drinkers; and had lower levels of urine protein compared to those in the lowest tertile (all P<0.001; Table 1). Those with higher adherence to the overall plant-based diet had a higher intake of healthy and unhealthy plant foods, carbohydrates, fiber, potassium, magnesium, vitamin A, vitamin C, and folate; and a lower intake of animal foods, protein, total fat, saturated fat, sodium, phosphate, zinc, vitamin B12, and dietary acid load per day compared to those in the lowest tertile of the overall plant-based diet index (all P<0.05; Table 2).

Table 1.

Participant characteristics by tertiles of the overall plant-based diet index in the Chronic Renal Insufficiency Cohort (CRIC) study^a (n=2,539)

Participant characteristic^a	Tertile 1, n=1,004	Tertile 2, n=792	Tertile 3, n=743	p-value
Median score (range)	46 (30 - 49)	52 (50 - 54)	57 (55 - 73)
Clinical center, n (%)
University of Pennsylvania	153 (15.2)	106 (13.4)	86 (11.6)	0.003
Johns Hopkins University	130 (12.9)	92 (11.6)	106 (14.3)
Case Western Reserve University	175 (17.4)	143 (18.1)	135 (18.2)
University of Michigan	174 (17.3)	126 (15.9)	120 (16.2)
University of Illinois at Chicago	142 (14.1)	95 (12.0)	91 (12.2)
Tulane University Health Science Center	95 (9.5)	63 (8.0)	54 (7.3)
Kaiser Permanente of Northern California	135 (13.4)	167 (21.1)	151 (20.3)
Age, years	56.3 (11.5)	58.5 (10.4)	59.8 (9.9)	<0.001
Male, n (%)	612 (61.0)	390 (49.2)	326 (43.9)	<0.001
Race, n (%)
Non-Hispanic white	520 (51.8)	414 (52.3)	371 (49.9)	0.06
Non-Hispanic black	401 (39.9)	310 (39.1)	302 (40.6)
Hispanic	54 (5.4)	31 (3.9)	28 (3.8)
Other	29 (2.9)	37 (4.7)	42 (5.7)
Education, n (%)
Less than high school	134 (13.3)	90 (11.4)	104 (14.0)	0.3
High school graduate	175 (17.4)	146 (18.4)	138 (18.6)
Some college	331 (33.0)	248 (31.3)	210 (28.3)
College graduate or higher	364 (36.3)	308 (38.9)	291 (39.2)
Income, n (%)
< $20,000	256 (25.5)	180 (22.7)	192 (25.8)	0.5
$20,001 - $50,000	236 (23.5)	211 (26.6)	187 (25.2)
$50,001-$100,000	220 (21.9)	182 (23.0)	170 (22.9)
> $100,000	141 (14.0)	96 (12.1)	80 (10.8)
Do not wish to answer	151 (15.0)	123 (15.5)	114 (15.3)
Body mass index (kg/m²)	32.4 (7.7)	32.1 (8.2)	31.1 (7.3)	<0.001
Obesity status (BMI ≥ 30 kg/m²), n (%)	591 (58.9)	426 (53.8)	371 (49.9)	<0.001
Physical activity (MET/wk)	207.1 (133.5)	197.2 (128.1)	198.2 (127.8)	0.2
Current smoker, n (%)	163 (16.2)	85 (10.7)	71 (9.6)	<0.001
Current drinking, n (%)	271 (27.0)	172 (21.7)	126 (17.0)	<0.001
Diabetes, n (%)	459 (45.7)	340 (42.9)	327 (44.0)	0.5
Hypertension, n (%)	848 (84.5)	684 (86.4)	613 (82.5)	0.1
History of cardiovascular disease, n (%)	326 (32.5)	247 (31.2)	238 (32.0)	0.8
Serum creatinine (mg/dL)	1.8 (0.7)	1.8 (0.6)	1.7 (0.6)	0.03
eGFR (mL/min/1.73 m²)	46.9 (18.2)	45.3 (15.7)	45.9 (16.5)	0.1
Total cholesterol (mg/dL)	182.2 (46)	183.2 (41.8)	181.4 (42)	0.7
24H urine protein (g/24h)	1.2 (2.4)	0.8 (2.0)	0.7 (1.6)	<0.001
ACE inhibitors or ARB use, n (%)	676 (67.3)	562 (71.0)	503 (67.7)	0.2
Serum potassium (mmol/L)	4.3 (0.5)	4.3 (0.5)	4.4 (0.5)	0.8
Serum bicarbonate (mEq/L)	24.5 (3.2)	24.6 (3.1)	24.8 (3.1)	0.07
Sodium bicarbonate pill use, n (%)	9 (0.9)	11 (1.4)	10 (1.3)	0.6

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Mean (standard deviation) reported for continuous variables, and n (%) reported for categorical variables, unless otherwise stated.

BMI, body mass index; ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; eGFR, estimated glomerular filtration rate using a CRIC-specific equation; MET, metabolic equivalent task

Table 2.

Nutritional characteristics by tertiles of the overall plant-based diet index in the Chronic Renal Insufficiency Cohort (CRIC) study (n=2,539)

Nutritional characteristic^a	Tertile 1, n=1,004	Tertile 2, n=792	Tertile 3, n=743	p-value
Healthy plant food (servings/day)	5.7 (3.8)	7.0 (4.2)	9.8 (5.2)	<0.001
Unhealthy plant food (servings/day)	6.9 (4.5)	7.0 (4.7)	8.1 (4.9)	<0.001
Animal food (servings/day)	9.4 (5.1)	6.7 (3.8)	5.5 (3.5)	<0.001
Total energy (kcal)	1,962.3 (792.5)	1,674.8 (756.2)	1,723.2 (740.9)	<0.001
Carbohydrates (% of energy)	45.3 (10.1)	51.4 (9.6)	56.1 (9.1)	<0.001
Protein (% of energy)	16.8 (4.1)	15.5 (3.6)	14.3 (3.0)	<0.001
Fat (% of energy)	36.8 (7.9)	33.4 (7.7)	31.3 (7.4)	<0.001
Saturated fat (% of energy)	11.8 (3.1)	10.3 (2.8)	9.3 (2.6)	<0.001
MUFA (% of energy)	14.1 (3.4)	12.7 (3.4)	11.9 (3.2)	<0.001
PUFA (% of energy)	8.1 (2.5)	7.8 (2.4)	7.7 (2.5)	0.006
Fiber (g/1000 kcal)	8.0 (2.8)	10.1 (3.5)	12.2 (4.0)	<0.001
Sodium (mg/1000 kcal)	1,627.2 (361.9)	1,590.7 (341.1)	1,556.8 (328.3)	<0.001
Potassium (mg/1000 kcal)	1,545.5 (418.0)	1,742.9 (431.1)	1,924.1 (472.0)	<0.001
Phosphate (mg/1000 kcal)	647.4 (141.9)	642.5 (142.2)	630.0 (133.3)	0.03
Calcium (mg/1000 kcal)	387.2 (158.6)	394.8 (151.2)	394.8 (130.3)	0.5
Magnesium (mg/1000 kcal)	154.9 (39.1)	176.0 (41.9)	195.4 (45.0)	<0.001
Zinc (mg/1000 kcal)	6.3 (2.5)	6.1 (2.2)	5.9 (2.0)	<0.001
Iron (mg/1000 kcal)	7.5 (2.1)	8.5 (2.5)	9.3 (2.7)	<0.001
Vitamin A (IU 1000 kcal)	4,148.5 (2,675.9)	5,330.4 (4,101.9)	6,522.4 (4,453.7)	<0.001
Vitamin C (mg/1000 kcal)	67.4 (46.8)	86.3 (54.9)	102.9 (56.9)	<0.001
Vitamin B12 (ug/1000 kcal)	2.90 (1.5)	2.61 (2.4)	2.14 (1.0)	<0.001
Folate (ug/1000 kcal)	190.9 (55.7)	221.8 (65.0)	247.7 (71.5)	<0.001
Dietary acid load (mEq/d)^b	6.4 (18.9)	−5.04 (15.7)	−14.9 (18.0)	<0.001
Whole grain (servings/day)	1.84 (2.13)	2.40 (2.50)	3.25 (3.10)	<0.001
Fruit (servings/day)	0.88 (1.24)	1.23 (1.36)	1.79 (1.51)	<0.001
Vegetable (servings/day)	1.11 (1.08)	1.22 (1.01)	1.70 (1.50)	<0.001
Nuts (servings/day)	0.57 (1.06)	0.63 (0.95)	0.94 (1.32)	<0.001
Legumes (servings/day)	0.19 (0.25)	0.26 (0.53)	0.35 (0.48)	<0.001
Coffee and tea (servings/day)	1.08 (1.63)	1.31 (1.56)	1.72 (1.80)	<0.001
Refined grain (servings/day)	2.45 (2.18)	2.50 (2.42)	2.86 (2.43)	<0.001
Potatoes (servings/day)	0.33 (0.32)	0.31 (0.32)	0.35 (0.35)	0.02
Fruit juice (servings/day)	0.50 (0.88)	0.60 (1.03)	0.75 (1.06)	<0.001
Sweetened beverage (servings/day)	2.25 (2.68)	2.26 (2.46)	2.43 (2.62)	0.3
Sweets and dessert (servings/day)	1.31 (1.66)	1.34 (1.65)	1.66 (1.66)	<0.001
Animal fat (servings/day)	0.27 (0.39)	0.15 (0.27)	0.11 (0.27)	<0.001
Dairy (servings/day)	1.47 (1.81)	1.22 (1.67)	0.99 (1.43)	<0.001
Eggs (servings/day)	0.58 (0.69)	0.38 (0.41)	0.27 (0.35)	<0.001
Fish or seafood (servings/day)	0.88 (0.93)	0.63 (0.73)	0.52 (0.63)	<0.001
Meat (servings/day)	5.99 (4.18)	4.13 (3.06)	3.43 (2.80)	<0.001
Miscellaneous animal food (servings/day)	0.25 (0.22)	0.19 (0.18)	0.17 (0.16)	<0.001

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Mean (standard deviation) reported for continuous variables, and n (%) reported for categorical variables. Food groups and components expressed as serving per day (serving/d)

MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid

Dietary acid load (potential renal acid load) =0.49×protein(g)+0.037×phosphorus(mg)−0.021×potassium(mg)−0.026×magnesium(mg)−0.013×calcium(mg).

Participants in the highest tertile of the healthy plant-based diet were more likely to be older and to have a college degree or higher level of education; and less likely to be white, obese, and current smokers (all P<0.05; Table S2). Those in the highest tertile of the healthy plant-based diet index consumed more healthy plant foods (such as whole grains, fruits, vegetables, nuts, legumes), fiber, potassium, phosphate, calcium, magnesium, iron, folate, vitamin A, and vitamin C; and consumed less unhealthy plant foods (such as refined grains, sweets and desserts), animal foods (such as animal fat and meat), sodium, vitamin B12, and dietary acid load in comparison to the lowest tertile of the healthy plant-based diet index (all P<0.05; Table S3).

Those in the highest tertile of the unhealthy plant-based diet were more likely to be younger, men, current smokers, to have a high school education or less, and to have a lower income; and they were less likely to be white and to have diabetes compared to the lowest tertile (all P<0.05; Table S4). Participants in the highest tertile of the unhealthy plant-based diet consumed lower amounts of healthy plant foods (such as fruits, vegetables, nuts, legumes), animal foods, fiber, sodium, potassium, calcium, magnesium, zinc, iron, vitamin A, vitamin B12, and folate; and consumed higher amounts of unhealthy plant foods (such as refined grains, sweets and desserts), and dietary acid load (all P<0.05; Table S5). The number of participants on sodium bicarbonate pills was small (approximately 1%). Serum levels of potassium, bicarbonate, and sodium bicarbonate pill use was not significantly different by any of the plant-based diet indices (all P>0.05), except participants in the highest vs. lowest tertiles of the healthy plant-based diet had a higher level of serum bicarbonate(24.9 vs. 24.4 mEq/L, respectively).

Plant-Based Diets and CKD Progression

During a median follow-up of 7 years, there were 977 cases of CKD progression. There was a lower incidence rate of CKD progression for higher levels of adherence to the overall plant-based diet index and the healthy plant-based diet index, and a higher incidence rate of CKD progression for higher levels of the unhealthy plant-based diet index (Table 3). After adjusting for sociodemographic, lifestyle, and clinical factors in model 1 and model 2, there was no statistically significant association between tertiles of any of the plant-based diet indices and CKD progression. In the continuous analysis, a 10-point higher score for the unhealthy plant-based diet index was associated with a 14% higher risk of CKD progression (Model 2 HR: 1.14, 95% CI, 1.03, 1.25, p=0.008).

Table 3.

Risk of CKD progression by tertiles of plant-based diet scores and per 10-point increase in diet score

Diet index	Tertiles of Plant-Based Diet Scores^a			P for trend	Per 10-point higher in Diet Score
Diet index	Tertile 1	Tertile 2	Tertile 3	P for trend	HR (95% CI)	P value
*Overall plant-based diet index*
n	1004	792	743
IR per 1000 PY	56.9 (51.6 to 62.8)	50.2 (44.8 to 56.2)	49.4 (43.9 to 55.6)
Model 1^b	1	0.93 (0.79 to 1.08)	0.94 (0.81 to 1.11)	0.4	0.98 (0.88 to 1.08)	0.7
Model 2^c	1	1.03 (0.88 to1.21)	1.12 (0.96 to 1.32)	0.2	1.04 (0.94 to 1.16)	0.4
*Healthy plant-based diet index*
n	930	883	726
IR per 1000 PY	56.1 (50.7 to 62.0)	53.09 (47.8 to 59.0)	47.3 (41.9 to 53.5)
Model 1^b	1	1.00 (0.86 to 1.16)	0.87 (0.73 to 1.02)	0.1	0.94 (0.86 to 1.04)	0.2
Model 2^c	1	0.97 (0.83 to 1.23)	0.86 (0.73 to 1.02)	0.1	0.93 (0.84 to 1.02)	0.1
*Unhealthy plant-based diet index*
n	961	801	777
IR per 1000 PY	45.3 (40.7 to 50.5)	57.25 (51.3 to 63.8)	57.15 (51.2 to 63.8)
Model 1^b	1	1.10 (0.94 to 1.28)	0.94 (0.80 to 1.11)	0.5	0.99 (0.90 to 1.08)	0.8
Model 2^c	1	1.12 (0.96 to 1.31)	1.11 (0.94 to 1.31)	0.3	1.14 (1.03 to 1.25)	0.008

Open in a new tab

P for trend was obtained from an interaction term between follow-up time and tertiles of plant-based diet indices as an ordinal variable.

Values given as n or HR (95% CI).

Model 1 was adjusted for clinical site, age, sex, race, education, income, and total energy intake, physical activity, smoking status, and alcohol use.

Model 2 was adjusted for covariates in model 1 plus obesity status (categorical variable with cut off at 30 kg/m²), kidney function (eGFR), 24-hour urinary protein, diabetes, hypertension, history of cardiovascular disease, and use of ACE inhibitors or ARBs.

IR, incidence rate; PY, person-years; HR, hazard ratio; 95% CI, 95% Confidence Interval.

Plant-Based Diets and All-Cause Mortality

During a median follow-up of 12 years, there were 836 deaths. The mortality rate was lowest for those in the highest tertile of adherence to the overall plant-based diet index and healthy plant-based diet index and higher for those in tertile 2 and tertile 3 of adherence to the unhealthy plant-based diet index relative to tertile 1 (Table 4).

Table 4.

Risk of all-cause mortality by tertiles of plant-based diet scores and per 10-point higher in plant-based diet score

Diet Index	Tertiles of Plant Based Diet Scores^a			P for Trend	Per 10-point higher in Diet Score
Diet Index	Tertile 1	Tertile 2	Tertile 3	P for Trend	HR (95% CI)	p value
*Overall plant-based diet index*
n	1004	792	743
IR per 1000 PY	34.2 (30.8 to 37.9)	28.9 (25.6 to 32.8)	28.0 (24.6 to 31.9)
Model 1^b	1	0.84 (0.71 to 0.99)	0.73 (0.62 to 0.87)	<0.001	0.83 (0.75 to 0.93)	<0.001
Model 2^c	1	0.84 (0.71 to 0.99)	0.74 (0.62 to 0.88)	<0.001	0.83 (0.74 to 0.92)	<0.001
*Healthy plant-based diet index*
n	930	883	726
IR per 1000 PY	30.5 (27.2 to 34.1)	31.6 (28.2 to 35.4)	29.9 (26.3 to 34.0)
Model 1^b	1	0.99 (0.83 to 1.17)	0.84 (0.70 to 1.00)	0.1	0.87 (0.78 to 0.96)	0.006
Model 2^c	1	0.95 (0.81 to 1.12)	0.79 (0.66 to 0.95)	0.03	0.83 (0.75 to 0.92)	<0.001
*Unhealthy plant-based diet index*
n	961	801	777
IR per 1000 PY	28.3 (25.2 to 31.7)	33.2 (29.5 to 37.3)	31.2 (27.6 to 35.1)
Model 1^b	1	1.03 (0.87 to 1.21)	1.03 (0.86 to 1.23)	0.6	1.02 (0.92 to 1.13)	0.7
Model 2^c	1	1.06 (0.90 to 1.25)	1.16 (0.97 to 1.38)	0.07	1.11 (1.00 to 1.23)	0.049

Open in a new tab

P for trend was obtained from an interaction term between follow-up time and tertiles of plant-based diet indices as an ordinal variable.

Values given as n or HR (95% CI).

Model 1 was adjusted for clinical site, age, sex, race, education, income, and total energy intake, physical activity, smoking status, and alcohol use.

IR, incidence rate; PY, person-years; HR, hazard ratio; 95% CI, 95% Confidence Interval.

Higher adherence to the overall plant-based diet index was associated with lower risk of all-cause mortality (model 2 HR for tertile 2 vs. 1: 0.84, 95% CI: 0.71, 0.99; HR for tertile 3 vs. 1: 0.74, 95% CI: 0.62, 0.88; p-trend <0.001). For each 10-point higher overall plant-based diet score, there was a 17% lower risk of all-cause mortality (HR: 0.83, 95% CI: 0.74, 0.92, p<0.001). There was an approximately linear inverse association between adherence to an overall plant-based diet and all-cause mortality (Figure 1).

Figure 1. — Adjusted hazard ratios and 95% CIs for all-cause mortality, according to the continuous overall plant-based diet index. The histogram shows the distribution of scores for the plant-based diet index in gray. The solid line represents the adjusted hazard ratio (log scale) for the association between overall plant-based diet index and all-cause mortality, modeled using linear spline terms with 1 knot at the 10th percentile of the overall plant-based diet index (score, 43), which was used as the reference point. The dashed lines represent the 95% confidence interval (log scale). Hazard ratios were adjusted for clinical site, age, sex, race, education, income, total energy intake, physical activity, smoking status, alcohol use, obesity status (categorical variable with cut off at 30 kg/m2), kidney function (eGFR), 24-hour urinary protein, diabetes, hypertension, history of cardiovascular disease, and use of ACE inhibitors or ARBs.

There was a consistent, statistically significant inverse association between adherence to a healthy plant-based diet and all-cause mortality. In model 2, those with the highest adherence to a healthy plant-based diet had a 21% lower risk of all-cause mortality (model 2 HR for tertile 3 vs. 1: 0.79, 95% CI: 0.66, 0.95, p-trend=0.03). For each 10-point higher score for the healthy plant-based diet, there was a 17% lower risk of all-cause mortality (model 2 HR: 0.83, 95% CI: 0.75, 0.92, p<0.001).

There was a slightly higher risk of all-cause mortality at higher levels of adherence to the unhealthy plant-based diet (model 2 HR per 10 points higher: 1.11, 95% CI: 1.00, 1.23, p=0.049).

In sensitivity analysis, there was no significant interaction between plant-based diets and education, and plant-based diets and income for CKD progression and all-cause mortality (P for interaction >0.05). In stratified analyses, the direction of association was consistent across all strata of education and income. When we used renal replacement therapy without eGFR decline as the outcome, the associations were comparable to the association with CKD progression. In the continuous analysis, a 10-point higher score for the unhealthy plant-based diet index was associated with a 10% higher risk of renal replacement therapy (Model 2 HR: 1.10, 95% CI: 0.99, 1.23, p=0.09). However, there was no significant association between any of the plant-based diet scores and renal replacement therapy. The results did not change when we adjusted BMI as a continuous variable, instead of a categorical variable.

When the food categories within plant-based diet scores were modeled together, per serving higher in healthy plant foods were associated with a 2% lower risk of all-cause mortality (HR: 0.98, 95% CI: 0.96 to 0.99, p=0.02) (Table S6). Per serving higher in vegetable intake was associated with 7% lower risk of all-cause mortality (HR: 0.93, 95% CI: 0.86 to 1.00, p=0.05). Per serving higher in sugar-sweetened beverage, dairy, and egg was associated with 3% (HR: 1.03, 95% CI: 1.00 to 1.06, p=0.03), 4% (HR: 1.04, 95% CI: 1.00 to 1.09, p=0.04), and 17% (HR: 1.17, 95% CI: 1.04 to 1.33, p=0.01) higher risk of all-cause mortality, respectively (Table S7). Individuals with higher vs. lower fiber intake (≥median vs. < median) had 20% (HR: 0.80, 95% CI: 0.70 to 0.91, p=0.001) and 27% (HR: 0.73, 95% CI: 0.63 to 0.84, p<0.001) lower risk of CKD progression and all-cause mortality, respectively (Table S8). Per interquartile range higher in potential renal acid load was not significantly associated with CKD progression and all-cause mortality.

In post-hoc analysis, there were 737 incident cases of cardiovascular disease over a median follow-up of 11 years. Per 10-point higher in unhealthy plant-based diet index was associated with 12% higher risk of incident cardiovascular disease (model 2 HR: 1.12, 95% CI: 1.00 to 1.25, p=0.04) (Table S9). We observed a significant trend for the association between healthy plant-based diet index and incident cardiovascular disease (p for trend=0.04), but there was no significant association between overall plant-based diet index, healthy plant-based diet index, and incident cardiovascular disease (p>0.05 for all tests). The associations between plant-based diet scores, CKD progression, and all-cause mortality were largely consistent across diabetes status, hypertension status, and history of cardiovascular disease (P for interaction >0.05 for all tests) (Figure S2). Only the association between healthy plant-based diet and all-cause mortality differed by history of cardiovascular disease (P for interaction=0.02).

DISCUSSION

In individuals with CKD, greater adherence to overall and healthy plant-based diets was associated with a lower risk of all-cause mortality, but not CKD progression and incident cardiovascular disease. Each 10-point higher score of unhealthy plant-based diets was associated with an elevated risk of CKD progression, all-cause mortality, and incident cardiovascular disease. These associations were consistent across individuals with diabetes, hypertension, and history of cardiovascular disease.

Our results on diet and all-cause mortality are consistent with prior studies. In individuals without CKD, higher adherence to a healthy plant-based and vegetarian diet was associated with a lower risk of incident CKD.¹¹ In a meta-analysis of 15,286 participants, dietary patterns rich in vegetables and fruits, legumes, whole grains, and fiber together with lower consumption of red meat, sodium, and refined sugars were consistently associated with lower risk of mortality in individuals with CKD.³ Similarly, in the CRIC population, greater adherence to a priori-defined healthy dietary patterns (Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, DASH diet, and Mediterranean diet) was associated with a lower risk of all-cause mortality.⁴ Our findings contribute to the literature by adding that dietary patterns that are generally high in plant foods, and dietary patterns that are high in healthful plant foods and low in unhealthful plant foods and animal foods can have health benefits in individuals with CKD.

Dietary acid load is an important mechanism through which plant-based diets may be associated with a lower risk of mortality in individuals with CKD. In our study, although potential renal acid load was not associated with CKD progression and all-cause mortality, per serving higher in foods high in dietary acid load (dairy, eggs) was associated with a greater risk of all-cause mortality. Participants with higher adherence to an overall plant-based diet and a healthy plant-based diet consumed more vegetables, fruits, nuts and legumes, and relatively low animal fat, dairy, eggs, seafood, and meat. Studies have reported that vegetables and nuts are associated with a lower risk of CKD progression by affecting phosphate and acid-base homeostasis thus resulting in lower dietary acid load.^19–21 A high acid load from dietary sources can be detrimental to the already damaged nephrons in CKD patients. In the setting of metabolic acidosis, the reduced number of nephrons compensate by increasing ammonia production and distal tubular acid excretion causing tubular toxicity. These adaptations further worsen kidney function and lead to progression of CKD.^22–24 Metabolic acidosis increases muscle catabolism and bone resorption, thus increasing the risk of pathological fractures.²⁵ Plant sources of protein including legumes and nuts have been associated with lower serum FGF-23 levels and higher levels of serum bicarbonate.¹⁹ FGF-23 is a hormone responsible for excretion of phosphate in the urine in the setting of low eGFR and has been observed to be a potent risk factor for mortality in patients with CKD.²⁶ Other studies have also demonstrated that plant protein may reduce metabolic acidosis in CKD patients.^27,28 The lack of an association between potential renal acid load and kidney and mortality outcomes in our study population may be attributed to inaccuracy in estimating acid load, because net endogenous acid production estimated using objective biomarkers (urea nitrogen, urinary potassium) was associated with higher risk of CKD progression in the CRIC Study.²⁹

Additionally, individuals with greater adherence to overall and healthy plant-based diets had higher intake of magnesium, which can lead to lower production of inflammatory cytokines and mitigation of endothelial dysfunction.³⁰ Consistent with this hypothesis, a study of 1,110 adults with CKD in the National Health and Nutrition Examination Survey (NHANES) reported that low adherence to a DASH diet was associated with a higher risk of CKD progression, and dietary potassium and magnesium mediated the association.³¹ We observed that the risk of CKD progression and mortality was higher for individuals with greater adherence to unhealthy plant-based diets (low in potassium and magnesium), highlighting the importance of consuming healthy plant foods (fruits, vegetables, whole grains, nuts, legumes, tea and coffee), and reducing the intake of sweetened beverage, dairy, and eggs.

We did not find a significant association between overall and healthy plant-based diets and CKD progression or incident cardiovascular disease. Prior studies on dietary patterns and CKD progression showed mixed results. In the CRIC study and NHANES, greater adherence to healthy dietary patterns was associated with a lower risk of CKD progression or end-stage kidney disease.^4,31 However, a meta-analysis found no significant association between healthy dietary patterns and risk of end-stage kidney disease in individuals with CKD.³ It is possible that overall and healthy plant-based diets may not be effective for delaying CKD progression, though studies of dietary components (red meat, sugar-sweetened beverages, fruits, and vegetables) suggest that diets high in plant foods and low in animal products can have positive impacts on kidney function.^32–34 Additionally. the range of plant food intake may be narrow in our study, considering that individuals with CKD may have been counseled to restrict the intake of certain plant foods which may be high in potassium.⁵ We were not able to directly compare the plant food intake to other studies,^11,16,32,33 because plant-based diet scores are rank-based and cohort-specific. In the future, it would be worthwhile deriving absolute cutoffs for healthy plant food, unhealthy plant food, and animal food intake to provide more precise dietary recommendations.

Unhealthy plant-based diets were high in refined grains, potatoes, fruit juices, sugar-sweetened beverages, sweets and desserts, and low in healthy plant foods, animal foods, which resulted in low fiber and micronutrient intake (vitamin A, folate, potassium magnesium). In our study, consumption of sugar-sweetened beverage was significantly associated with all-cause mortality, whereas higher fiber intake was associated with a lower risk of CKD progression and all-cause mortality. Previous studies linked unhealthy plant-based diets to adverse health outcomes, including incident diabetes, hypertension, and coronary heart disease.^7,8,16 In addition to low diet quality, it is important to note that those with greater adherence to unhealthy plant-based diets consume more ultraprocessed foods (foods formulated using industrial substances such as sugar-sweetened beverages, sweets, and desserts). In the CRIC cohort, greater consumption of ultraprocessed foods was associated with a higher risk of all-cause mortality and CKD progression.³⁴ Changes in the gut microbiota, which could increase inflammation and production of uremic toxins, and compounds generated during processing (glycation end-products) have been suggested as potential mechanisms through which highly processed foods are associated with adverse health outcomes.³⁴ Taken together, our findings provide support for reducing consumption of unhealthy plant foods, such as sugar-sweetened beverages, and increasing consumption of fiber-rich foods to lower the risk of CKD progression.

There are notable strengths of this study. We included a large sample size of participants with CKD, which is novel considering that prior literature on plant-based diets has focused on generally healthy individuals. Prior studies were limited in their representation of individuals with diabetes, whereas about half of our study population consisted of individuals with diabetes, which is a common co-morbidity of CKD. Participants were recruited from various sites, thereby providing geographic, racial, and economic diversity. Participants were observed for a long follow-up period; and clinically relevant measures of CKD progression and mortality were rigorously collected.

There are, however, several limitations associated with our study. First, participants self-reported dietary intake, which may be subject to measurement error. The DHQ was developed many years ago, and, as such, does not reflect newer plant-based food items that have been recently introduced in the food supply. Second, study participants were excluded due to missing covariates, dietary data, or outcome data. Such exclusions may have limited generalizability of our findings. Third, dietary patterns were only assessed at baseline, and our analysis did not account for potential changes in diet over time. Lastly, residual confounding may exist within our observational study.

For future research, it would be beneficial to conduct studies which can incorporate data on currently available plant-based foods in the U.S. food supply. It would also be beneficial to investigate whether a plant-based diet intervention is effective in improving kidney parameters and other cardiometabolic health metrics.

In conclusion, higher adherence to an overall plant-based diet and a healthy plant-based diet was associated with a reduced risk of all-cause mortality but not CKD progression or incident cardiovascular disease in a population of kidney disease patients. Per 10-point higher in unhealthy plant-based diets was associated with a higher risk of all-cause mortality, CKD progression, and incident cardiovascular disease. Adhering to a plant-based diet may prolong life. It is unclear if overall and healthy plant-based diets can delay CKD progression once kidney disease has become overt, but unhealthy plant-based diets may be detrimental to kidney health. These results suggest quality of plant-based diets may be important for CKD management. In individuals with CKD, efforts to increase consumption of high-quality plant-based diets should be facilitated by promoting equitable access to healthy plant foods.

Supplementary Material

Figure S1. Flow chart of study participant selection

Figure S2. Associations between plant-based diet scores (per 10-point higher) and risk of CKD progression by presence of comorbidities.

Table S1. Description of food items within each food group for creating plant-based diet scores

Table S2. Baseline characteristics by tertiles of healthy plant-based diet index in the Chronic Renal Insufficiency Cohort study

Table S3. Nutritional characteristics by tertiles of healthy plant-based diet index in the Chronic Renal Insufficiency Cohort Study

Table S4. Baseline characteristics by tertiles of unhealthy plant-based diet index in the Chronic Renal Insufficiency Cohort study

Table S5. Nutritional characteristics by tertiles of unhealthy plant-based diet index in the Chronic Renal Insufficiency Cohort study

Table S6. Association between food categories (per serving higher) within plant-based diet scores in the Chronic Renal Insufficiency Cohort Study

Table S7. Association between 17 food groups (per serving higher) within plant-based diet scores in the Chronic Renal Insufficiency Cohort Study

Table S8. Associations between fiber intake (≥ median vs. < median, 1g/1000 kcal higher), potential renal acid load (PRAL), CKD progression, and all-cause mortality

Table S9. Risk of incident CVD by tertiles of plant-based diet scores and per 10-point increase in diet score

NIHMS1947337-supplement-1.pdf^{(828.4KB, pdf)}

Acknowledgements:

The authors thank the staff and participants of the Chronic Renal Insufficiency Cohort (CRIC) Study for their important contributions. We thank Dr Edward Horwitz for serving as a supervising co-investigator for CRIC research activities at one of the clinical sites (The MetroHealth System) and providing, input into CRIC study design.

Support:

Funding for the Chronic Renal Insufficiency Cohort Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award (CTSA) National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) grant UL1TR000003, Johns Hopkins University grant UL1 TR-000424, University of Maryland grant GCRC M01 RR-16500, the Clinical and Translational Science Collaborative of Cleveland, grant UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research grant UL1TR000433, University of Illinois at Chicago CTSA grant UL1RR029879, Tulane Center of Biomedical Research Excellence for Clinical and Translational Research in Cardiometabolic Diseases grant P20 GM109036, and Kaiser Permanente NIH/National Center for Research Resources University of California San Francisco-Clinical & Translational Science Institute grant UL1 RR-024131. Dr. Rebholz was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R03 DK128386) and the National Heart, Lung, and Blood Institute (R01 HL153178). Dr. Kim was supported by a grant from the NHLBI (K01 HL168232). Dr. Dobre was supported by R01 HL141846 from the National Heart, Lung, and Blood Institute. The funders had no role in study design, data collection, analysis, reporting, or the decision to submit for publication.

Financial Disclosure:

Dr. Appel receives payments from Wolters Kluwer for chapters in UpToDate on the relation of blood pressure with weight, exercise, smoking, and sodium intake. Dr. Navaneethan reported receiving personal fees from ACI clinical (event adjudication committee), AstraZeneca (Data safety monitoring board) Bayer, Boehringer Ingelheim/Eli Lilly, GlaxoSmithKline, Intercept (event adjudication committee), Vertex (event adjudication committee), and Vifor. Dr. Dobre received consultancy fee from CareDx, Inc. The other authors declare that they have no relevant financial interests.

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Additional Information: Author LJA is a CRIC Investigator.

Disclaimer: Some of the data reported here have been supplied by the US Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government.

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