8109361437Am J NephrolAm. J. Nephrol.American journal of nephrology0250-80951421-967029525790590615610.1159/000487715NIHMS949425ArticleRace/Ethnicity, Dietary Acid Load and Risk of ESRD among U.S. Adults with CKDCrewsDeidra C.MD, ScM1BanerjeeTanushreePhD2WessonDonald E.MD3MorgensternHalPhDSaranRajivMD, MS56BurrowsNilka RíosMPH7WilliamsDesmond E.MD, PhD8PoweNeil R.MD, MPH, MBA29for the Centers for Disease Control and Prevention Chronic Kidney Disease Surveillance Team Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore MD; Johns Hopkins Center for Health Equity, Johns Hopkins Medical Institutions, Baltimore MD, U.S.A Division of General Internal Medicine, Department of Medicine, University of California, San Francisco CA, U.S.A Diabetes Health and Wellness Institute, Baylor Scott and White Health, Dallas, TX, U.S.A Departments of Epidemiology and Environmental Health Sciences, School of Public Health, and Department of Urology, Medical School, University of Michigan, Ann Arbor MI, U.S.A Kidney Epidemiology & Cost Center, University of Michigan, Ann Arbor MI, U.S.A Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor MI, U.S.A Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA, U.S.A Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, U.S.A Department of Medicine, San Francisco General Hospital, San Francisco, California, U.S.ACorresponding Author: Deidra C. Crews, MD, ScM, Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, 301 Mason F. Lord Drive, Suite 2500, Baltimore, Maryland 21224, U.S.A2232018093201820180932019473174181Background

Dietary acid load (DAL) confers risk for CKD and CKD progression. We sought to determine the relation of DAL to racial/ethnic differences in risk of ESRD among persons with CKD.

Methods

Among 1123 non-Hispanic black (NHB) and white (NHW) National Health and Nutrition Examination Survey III participants with estimated glomerular filtration rate 15-59 ml/min/1.73 m2, DAL was estimated using the Remer and Manz net acid excretion (NAEes) formula and 24-hour dietary recall. ESRD events were ascertained via linkage with Medicare. A competing risk model (accounting for death) was used to estimate the hazard ratio (HR) for treated ESRD, comparing NHBs with NHWs, adjusting for demographic, clinical and nutritional factors (body surface area, total caloric intake, serum bicarbonate, protein intake), and NAEes. Separately, whether the relation of NAEes with ESRD risk varied by race/ethnicity was tested.

Results

At baseline, NHBs had greater NAEes (50.9 vs. 44.2 mEq/d) than NHWs. Fully, 22% developed ESRD over a median of 7.5 years. The unadjusted HR comparing NHBs to NHWs was 3.35 [95% confidence interval (CI), 2.51-4.48]; adjusted HR (for factors above): 1.68 (CI 1.18-2.38). A stronger association of NAE with risk of ESRD was observed among NHBs (adjusted HR per mEq/d increase in NAE 1.21, CI 1.12-1.31) than among NHWs (HR 1.08, CI 0.96-1.20), p interaction for race/ethnicity*NAEes=0.004.

Conclusions

Among U.S. adults with CKD, the association of DAL with progression to ESRD is stronger among NHBs than NHWs. DAL is worthy of further investigation for its contribution to kidney outcomes across race/ethnic groups.

INTRODUCTION

Blacks experience more rapid decline in kidney function than whites[1, 2] and have a greater risk of end stage renal disease (ESRD)[3, 4]. While the contributions of apolipoprotein L1 (APOL1) risk variants to racial disparities in chronic kidney disease (CKD) have received recent attention [1, 5], focus on the potential role of modifiable risk factors, such as diet, in these disparities is also warranted[6].

High dietary acid load (DAL) is associated with adverse kidney outcomes[7–9]; and interventional studies have shown that alkaline diets (e.g. rich in fruits and vegetables) confer benefits to the kidney[10–12]. Explanatory mechanisms underlying the association of DAL and kidney injury may include tubular toxicity of elevated ammonium concentration[13], increased endothelin and aldosterone[14–16], and increased angiotensin II activity[17], with the latter agents yielding the physiologic benefit of increased distal nephron acidification but with the attendant pathophysiologic consequence of long-term kidney injury.

We reported in a nationally representative sample that non-Hispanic black (NHB) race was associated with higher DAL than non-Hispanic white (NHW) race[9] and high DAL was associated with increased risk of ESRD among U.S. adults with CKD.[8] However, the relationship of racial differences in DAL to racial disparities in CKD progression is unknown. Understanding these relationships could inform interventions designed to mitigate disparities in ESRD risk.

The objective of the present study was to determine the contribution of racial differences in DAL, quantified by dietary net acid excretion (NAEes), to the more rapid progression to ESRD observed among NHBs as compared to NHWs[3, 4]. We also sought to determine whether the association of DAL and risk of ESRD varied by race. Our study was conducted among a nationally representative sample of U.S. adults with CKD stages 3 or 4[18] using data from the National Health and Nutrition Examination Survey (NHANES) III, with follow up for ESRD outcomes.

METHODSStudy Population and Baseline Data

NHANES III was a national probability sample of 34,955 United States non-institutionalized civilians conducted between 1988 and 1994 by the Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS). For this analysis, we included NHB and NHW participants ≥20 years of age (n=14,223) who did not have missing data on dietary intake (n=12,279), had an eGFR ≥15 and <60 ml/min per 1.73 m2 (n=1,261), and were not pregnant (final n=1,123). NHANES III participants provided informed consent.

Sociodemographic and Clinical Measurements

Medical history and demographic data were collected through a standardized survey conducted at participants’ homes followed by a medical examination and laboratory testing that occurred in the mobile examination center.[19] Sociodemographic factors were assessed during the interview. Racial/ethnic categories were self-reported by participants. Self-reported information on socioeconomic position (education and income) was obtained during the interview portions of the survey. Income was assessed using the poverty income ratio (PIR), a ratio of household income to household poverty level.[19] Diabetes was defined by self-report or measured hemoglobin A1c ≥6.5%.[20] Hypertension was defined by self-report, a measured average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg, or reported use of antihypertensive medication.[21]

Measurement and Classification of Serum Bicarbonate and Kidney Parameters

Serum bicarbonate was measured by the phosphoenolpyruvate method using the Hitachi 737 multichannel analyzer (Boehringer Mannheim Diagnostics, Indianapolis, IN). Serum creatinine measurements which were obtained using a kinetic rate Jaffé method in NHANES III were recalibrated to standardized creatinine measurements obtained at the Cleveland Clinic Research Laboratory (Cleveland, OH) as standard creatinine=0.184+0.9603NHANES III-measured serum creatinine.[22] Random spot urine samples were obtained and frozen. Urine albumin was measured using a solid-phase fluorescence immunoassay, and urine creatinine was measured using the modified Jaffé kinetic method in the same laboratory. Estimated GFR was calculated using the isotope dilution mass spectrometry traceable four-variable MDRD Study equation for calibrated creatinine.[23] Albuminuria, which was determined by the urinary albumin-to-creatinine ratio (ACR), was expressed as milligrams of albumin per gram of creatinine using American Diabetes Association categories: normal (<30mg/g) and albuminuria (≥30 mg/g).[24]

Dietary Assessment and DAL

Dietary intake data collected in NHANES III were used to estimate the types and amounts of foods and beverages consumed during the 24-hour period before the interview (midnight to midnight) and estimate intake of energy and nutrients from those foods and beverages. The non-bicarbonate anions (protein and phosphorus) intake and the mineral cations (potassium, magnesium, and calcium) intake of foods consumed by participants were derived from the dietary intake data. Potential renal acid load (PRAL) of foods reported by the participants was calculated using the model by Remer and Manz, [PRAL (mEq/d)=0.493 protein (g) + 0.0373 phosphorus (mg)] 20.0213 potassium (mg) 20.0263 magnesium (mg) 20.01253 calcium (mg)][25]. DAL was estimated as NAEes (mEq/d) =PRAL+ organic acids (OAs), where OA was calculated as OA (mEq/d)=(BSA (m2) × 41 (mEq/d per 1.73 m2)/1.73 m2)[25], as used in our previous work.[8, 9, 26]

Outcome Ascertainment

Our primary outcome of interest was progression to ESRD. In NHANES III, ESRD was defined as initiation of chronic dialysis. ESRD events and mortality follow-up data from the time of the survey (1988–1994) through December 31, 2006 were determined from the Medicare ESRD Registry and National Death Index, which were linked to NHANES III data.[27] ESRD data are available for those NHANES respondents who agreed to provide personal identification data to NCHS and for whom NCHS was able to match with United States Renal Data System administrative records.

Statistical Analyses

Baseline characteristics of study participants stratified by NHB and NHW race/ethnicity were compared using chi-squared tests for categorical variables. For continuous variables, we checked normality assumptions and used one-way analysis of variance for normally distributed variables. In cases where the assumptions were not met, we used the Kruskal-Wallis test for continuous variables. We investigated the association of race with the development of ESRD, while accounting for the competing risk of death prior to ESRD using the method by Fine and Gray.[28] We estimated the hazard ratio of ESRD with linear and quadratic terms for NAEes in our multivariable Cox regression models to assess relation of DAL and the rate of ESRD among race groups. We assessed the proportionality of each categorical covariate by plotting log(-log(survival)) versus log of survival time and survival function versus survival time. We tested proportionality of continuous variables using Schoenfeld residual plots and examined their statistical significance. Product terms were used to examine possible effect modification by race/ethnicity (race/ethnicity*NAEes). All analyses included the NHANES survey sample weights to account for the complex sample design of the survey, and we followed the analytical guidelines for NHANES III data as proposed by the Centers for Disease Prevention and Control.[29] Results were considered statistically significant if P<0.05. All analyses were performed using SAS 9.2 (SAS Institute, Inc., Cary, NC).

Sensitivity Analysis

We conducted sensitivity analyses wherein we defined CKD stages 3 and 4 using eGFR calculated from the creatinine-based CKD-EPI equation[30] and repeated our primary analyses.

RESULTSParticipant Characteristics

A total of 1,123 NHB and NHW NHANES III participants with an estimated glomerular filtration rate (eGFR) between 15 and 59 ml/min/1.73 m2 were included in our study. There were no major differences in the sociodemographic and clinical characteristics of the participants who were included and those who were excluded, except age–those included had a mean age of 69.5 years compared to 75.4 years for those excluded.

NHBs and NHWs differed on several characteristics examined (Table 1). NHBs were younger, more likely to live in poverty, less likely to have completed more than high school and more likely to have diabetes and/or hypertension than were NHWs. Compared with NHWs, NHBs had a greater baseline prevalence of albuminuria and a slightly lower median eGFR. The median estimated DAL, calculated as NAEes, was 46.3 mEq/d [interquartile range (IQR) 34.6–58.4 mEq/day] for the full sample, and NHBs had higher PRAL and NAEes than NHWs.

Associations of Race and Dietary Acid Load with risk of ESRD

A total of 248 (22.1%) participants developed ESRD over a median of 7.5 (IQR 4.5 to 12.4) years of follow-up, including 154 (43.9%) NHBs and 94 (12.2%) NHWs. In unadjusted Cox regression models accounting for the competing risk of death, NHBs had greater risk of ESRD than NHWs [hazard ratio (HR) 3.35, 95% confidence interval (CI) 2.51-4.48] (Table 2). Subsequent models adjusting for covariates yielded an attenuated association of NHB race with risk of ESRD, with a HR of 1.68, 95% CI 1.18-2.38 in our final model, which was adjusted for socio-demographic (age, sex and poverty income ratio), clinical (diabetes, hypertension, eGFR and ACR) and nutritional (body surface area, total caloric intake, serum bicarbonate, protein intake and NAEes) factors. Effect modification by race/ethnicity×NAEes was observed, with a p value of 0.004 for the interaction in our final model. We proceeded by fitting separate models for NHBs and NHWs (Table 3). The estimated adjusted HR of ESRD for each 1 mEq/day increase in NAEes was 1.21 (95% CI 1.12-1.31) among NHBs and 1.08 (95% CI 0.96-1.20) among NHWs.

Sensitivity Analyses

When we defined CKD stages 3 and 4 using GFR estimated from the CKD Epidemiology Collaboration (CKD-EPI) equation (n=991) (Table 4), results were similar to our models using the Modification of Diet in Renal Disease (MDRD) Study equation. In unadjusted Cox regression models accounting for the competing risk of death, NHBs had greater risk of ESRD than NHWs (HR 2.48, 95% CI 1.81-3.39). In our fully adjusted model, the HR was 1.91, 95% CI 1.28-2.84, and effect modification by race/ethnicity×NAEes was observed (p interaction 0.03). In race/ethnicity-specific models, the adjusted HR for ESRD associated with NAEes was 1.28 (95% CI 1.17-1.40) among NHBs and 1.10 (95% CI 0.90-1.28) among NHWs.

DISCUSSION

Among a nationally representative sample of NHB and NHW U.S. adults with CKD, we found that NHBs had greater DAL than NHWs. DAL contributed little to explaining NHBs greater risk of progression to ESRD beyond traditional risk factors, although the association of DAL with risk of ESRD was stronger among NHBs than among NHWs. Our findings were robust to adjustment for multiple potential confounders of the associations of race/ethnicity, diet and CKD progression, including albuminuria and total caloric intake, and to definition of CKD (using MDRD versus CKD-EPI).

This is among the first studies examining the role of diet in racial disparities in CKD progression. Our work advances the findings of prior studies documenting poorer diet quality among blacks, including their lower likelihood of following a Dietary Approaches to Stop Hypertension (DASH) trial-accordant diet than whites[31, 32], despite there being shown the potential of blacks to derive the greatest blood pressure lowering benefit from the diet.[33] The DASH diet, which is high in fruits and vegetables, moderate in low-fat dairy products, and low in animal protein, but with substantial amounts of plant protein from legumes and nuts[34], is low in DAL[35], and is associated with lower risk of CKD[32] and kidney function decline[36]. Lower rates of blacks, as compared to whites, following diets low in DAL may be, in part, due to their greater socioeconomic barriers to healthful eating. For example, in 2011, 35% of African Americans lived below the US federal poverty threshold ($22,350 annually for a family of four), compared to 13% of whites.[37] Other potential reasons for poorer diet quality among African Americans compared to whites include African Americans’ perceptions of healthful dietary practices, cultural and familial norms, and preferences.[38–40]

Our finding of a stronger association between DAL and risk of ESRD among NHBs could be due to unaccounted for differences between NHBs and NHWs with CKD in the United States–including cause of CKD. In our study, NHBs with CKD were about 7 years younger, were more likely to have diabetes and/or hypertension, and were substantially more likely to have albuminuria than NHWs. It is therefore very likely that the causes of CKD differed between the two race groups. We would expect, for example, given the estimated prevalence of high risk APOL1 alleles among persons with CKD who are African American (19%)[5], that a substantial proportion of our NHB study population had high risk APOL1 alleles and therefore a greater prevalence of focal segmental glomerulosclerosis[41] than NHWs. In a study examining potential modifiers of the association of high risk APOL1 variants with CKD progression among African Americans with hypertension-attributed kidney disease, high risk APOL1 variant status was associated with a 2.3 times greater hazard of CKD progression among individuals with lower DAL (as estimated by net endogenous acid production). In contrast, among individuals with higher DAL, high risk APOL1 variant status was minimally associated with CKD progression [HR 1.41, 95% CI 0.97-2.07][42], suggesting that in the setting of poor diet quality, CKD progression is less attributable to this genetic risk factor. Based upon this study and ours, the relation of dietary factors to the APOL1-associated risk of CKD progression among African Americans may warrant further study.

Another potential explanation for our findings is related to the potential effects of DAL on blood pressure. Based upon data from animal models[15, 43, 44], high DAL is postulated to lead to increases in angiotensin II, endothelin-1 and aldosterone, which can ultimately lead to blood pressure elevation as well as kidney fibrosis. NHBs with CKD and hypertension have poorer blood pressure control than NHWs with the same conditions[45], which in part, might be mediated by dietary factors, among other factors.

The limitations of our study warrant consideration. First, error in measuring diet in NHANES could have biased our findings, particularly if it varied by race/ethnicity. Second, we lacked longitudinal measures of dietary patterns and other potential time-varying mediators of the association of diet with CKD progression, including blood pressure and glycemic control. Third, we lacked several measures that may have differentially influenced NHBs and NHWs risk of progression to ESRD. These include constitutional factors such as the aforementioned genetic risk factors, as well as social determinants of health closely linked to diet and/or race that were not examined in our study, such as residential segregation[46] and discrimination[47]. Fourth, we were unable to account for differences in rates of pre-emptive kidney transplantation, which is performed for relatively few U.S. patients each year (2192 patients in 2009) but at unequal rates across race/ethnicities.[48] We do not believe this substantially influenced our results, however, as we observed similar racial differences in progression to ESRD (defined by dialysis initiation) as have been previously reported.[3, 49, 50] Fifth, our study only included NHBs and NHWs. Future studies with greater representation of multiple race/ethnicity groups might further examine this question. The strengths of our study included its longitudinal design; the examination of a potentially modifiable contributor to racial disparities in CKD progression and a potential pathophysiologic mechanism to account for DAL and progression to ESRD; and the consideration of mortality during follow up.

Dietary approaches may warrant further consideration as therapeutic targets for CKD patients, including those at high risk for progression. Together with other interventions, such as blood pressure control, DAL may be an important target for addressing the greater risk of CKD progression among NHBs. Evidence pointing to the potential benefits of healthful diets in slowing CKD progression is mounting; however, many individuals face barriers to following such dietary patterns, including food insecurity[51] and a lack of healthful foods in neighborhood stores[46]. Thus, dietary interventions targeting populations at high risk of CKD progression, such as NHBs, might better serve these populations if contextual factors posing challenges to making lifestyle modifications are addressed[38].

This work was supported by contract NU58DP006255-01-00 of the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Dr. Crews was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Grant K23-DK097184.

Disclosures: The authors report no conflicts of interest relative to this manuscript.

PeraltaCABibbins-DomingoKVittinghoffELinFFornageMKoppJBWinklerCAAPOL1 Genotype and Race Differences in Incident Albuminuria and Renal Function DeclineJ Am Soc Nephrol201627388789326180129PeraltaCAVittinghoffEBansalNJacobsDJrMuntnerPKestenbaumBLewisCSiscovickDKramerHShlipakMTrajectories of kidney function decline in young black and white adults with preserved GFR: results from the Coronary Artery Risk Development in Young Adults (CARDIA) studyAm J Kidney Dis201362226126623473985McClellanWMWarnockDGJuddSMuntnerPKewalramaniRCushmanMMcClureLANewsomeBBHowardGAlbuminuria and racial disparities in the risk for ESRDJ Am Soc Nephrol20112291721172821868498

System USRD: Annual Data Report.

ParsaAKaoWHXieDAstorBCLiMHsuCYFeldmanHIParekhRSKusekJWGreeneTHAPOL1 risk variants, race, and progression of chronic kidney diseaseN Engl J Med2013369232183219624206458CrewsDCPfaffTPoweNRSocioeconomic factors and racial disparities in kidney disease outcomesSeminars in nephrology201333546847524119852SciallaJJAppelLJAstorBCMillerER3rdBeddhuSWoodwardMParekhRSAndersonCAAfrican American Study of Kidney D, Hypertension Study GNet endogenous acid production is associated with a faster decline in GFR in African AmericansKidney international201282110611222475819BanerjeeTCrewsDCWessonDETileaAMSaranRRios-BurrowsNWilliamsDEPoweNRCenters for Disease C, Prevention Chronic Kidney Disease Surveillance THigh Dietary Acid Load Predicts ESRD among Adults with CKDJournal of the American Society of Nephrology : JASN20152671693170025677388BanerjeeTCrewsDCWessonDETileaASaranRRios BurrowsNWilliamsDEPoweNRCenters for Disease C, Prevention Chronic Kidney Disease Surveillance TDietary acid load and chronic kidney disease among adults in the United StatesBMC Nephrol20141513725151260GorayaNSimoniJJoCWessonDEDietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathyKidney international2012811869321881553GorayaNSimoniJJoCHWessonDETreatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rateKidney Int20148651031103824694986GorayaNSimoniJJoCHWessonDEA comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonateClinical journal of the American Society of Nephrology : CJASN20138337138123393104NathKAHostetterMKHostetterTHIncreased ammoniagenesis as a determinant of progressive renal injuryAm J Kidney Dis19911766546572042643PhisitkulSKhannaASimoniJBroglioKSheatherSRajabMHWessonDEAmelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFRKidney Int201077761762320072112WessonDESimoniJAcid retention during kidney failure induces endothelin and aldosterone production which lead to progressive GFR decline, a situation ameliorated by alkali dietKidney Int201078111128113520861823WessonDESimoniJBroglioKSheatherSAcid retention accompanies reduced GFR in humans and increases plasma levels of endothelin and aldosteroneAm J Physiol Renal Physiol20113004F83083721270096WessonDEJoCHSimoniJAngiotensin II-mediated GFR decline in subtotal nephrectomy is due to acid retention associated with reduced GFRNephrol Dial Transplant201530576277025527741KDOQI Clinical Practice Guidelines for chronic kidney disease: evaluation, classification and stratification[http://www2.kidney.org/professionals/KDOQI/guidelines_ckd/toc.htm]Plan and operation of the Third National Health and Nutrition Examination Survey, 1988-94Series 1: Programs and collection procedures1Vital Health Stat19941407International Expert CInternational Expert Committee report on the role of the A1C assay in the diagnosis of diabetesDiabetes care20093271327133419502545ChobanianAVBakrisGLBlackHRCushmanWCGreenLAIzzoJLJrJonesDWMatersonBJOparilSWrightJTJrThe Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 reportJAMA2003289192560257212748199CoreshJSelvinEStevensLAManziJKusekJWEggersPVan LenteFLeveyASPrevalence of chronic kidney disease in the United StatesJAMA2007298172038204717986697LeveyASCoreshJGreeneTMarshJStevensLAKusekJWVan LenteFChronic Kidney Disease Epidemiology CExpressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine valuesClin Chem200753476677217332152MolitchMEDeFronzoRAFranzMJKeaneWFMogensenCEParvingHHSteffesMWAmerican Diabetes ANephropathy in diabetesDiabetes care200427Suppl 1S798314693934RemerTManzFPotential renal acid load of foods and its influence on urine pHJ Am Diet Assoc19959577917977797810RebholzCMCoreshJGramsMESteffenLMAndersonCAAppelLJCrewsDCDietary Acid Load and Incident Chronic Kidney Disease: Results from the ARIC StudyAmerican journal of nephrology201542642743526789417Statistics NCfHThe Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality File: Matching MethodologyHyattsville, MDNational Center for Health Statistics2005FineJPGrayRJA proportional hazards model for the subdistribution of a competing riskJournal of the American Statistical Association199994446496509National Center for Health StatisticsAnalytical and Reporting Guidelines: The Third National Health and Nutrition Examination Survey, 1988-1994Hyattsville, Maryland1996LeveyASStevensLASchmidCHZhangYLCastroAF3rdFeldmanHIKusekJWEggersPVan LenteFGreeneTA new equation to estimate glomerular filtration rateAnn Intern Med2009150960461219414839MellenPBGaoSKVitolinsMZGoffDCJrDeteriorating dietary habits among adults with hypertension: DASH dietary accordance, NHANES 1988-1994 and 1999-2004Arch Intern Med2008168330831418268173CrewsDCKuczmarskiMFMillerER3rdZondermanABEvansMKPoweNRDietary habits, poverty, and chronic kidney disease in an urban populationJournal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation2015252103110SvetkeyLPSimons-MortonDVollmerWMAppelLJConlinPRRyanDHArdJKennedyBMEffects of dietary patterns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trialArch Intern Med199915932852939989541AppelLJMooreTJObarzanekEVollmerWMSvetkeyLPSacksFMBrayGAVogtTMCutlerJAWindhauserMMA clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research GroupN Engl J Med199733616111711249099655SciallaJJAndersonCADietary acid load: a novel nutritional target in chronic kidney disease?Adv Chronic Kidney Dis201320214114923439373LinJHuFBCurhanGCAssociations of diet with albuminuria and kidney function declineClin J Am Soc Nephrol20105583684320299364U.S. Census BureauCurrent Population Reports, P60-243, Income, Poverty, and Health Insurance Coverage in the United States: 2011Washington, DC2012JohnsonAEBoulwareLEAndersonCAChit-ua-areeTKahanKBoyerLLLiuYCrewsDCPerceived barriers and facilitators of using dietary modification for CKD prevention among African Americans of low socioeconomic status: a qualitative studyBMC nephrology20141519425481019AirhihenbuwaCOKumanyikaSAgursTDLoweASaundersDMorssinkCBCultural aspects of African American eating patternsEthn Health1996132452609395569TirodkarMAJainAFood messages on African American television showsAm J Public Health200393343944112604491GenoveseGFriedmanDJRossMDLecordierLUzureauPFreedmanBIBowdenDWLangefeldCDOleksykTKUscinski KnobALAssociation of trypanolytic ApoL1 variants with kidney disease in African AmericansScience2010329599384184520647424ChenTKChoiMJKaoWHAstorBCSciallaJJAppelLJLiLLipkowitzMSWolfMParekhRSExamination of Potential Modifiers of the Association of APOL1 Alleles with CKD ProgressionClin J Am Soc Nephrol201510122128213526430087WessonDEJoCHSimoniJAngiotensin II receptors mediate increased distal nephron acidification caused by acid retentionKidney Int201282111184119422832514PhisitkulSHackerCSimoniJTranRMWessonDEDietary protein causes a decline in the glomerular filtration rate of the remnant kidney mediated by metabolic acidosis and endothelin receptorsKidney Int200873219219917978813PlantingaLCMillerER3rdStevensLASaranRMesserKFlowersNGeissLPoweNRCenters for Disease C, Prevention Chronic Kidney Disease Surveillance TBlood pressure control among persons without and with chronic kidney disease: US trends and risk factors 1999-2006Hypertension2009541475619470881FrancoMDiez RouxAVGlassTACaballeroBBrancatiFLNeighborhood characteristics and availability of healthy foods in BaltimoreAm J Prev Med200835656156718842389BeydounMAPoggi-BurkeAZondermanABRostantOSEvansMKCrewsDCPerceived Discrimination and Longitudinal Change in Kidney Function Among Urban AdultsPsychosomatic medicine201779782483428445210GramsMEMassieABCoreshJSegevDLTrends in the timing of pre-emptive kidney transplantationJ Am Soc Nephrol20112291615162021617118WhittleJCWheltonPKSeidlerAJKlagMJDoes racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease?Arch Intern Med19911517135913642064486HsuCYLinFVittinghoffEShlipakMGRacial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United StatesJ Am Soc Nephrol200314112902290714569100JohnsTSEstrellaMMCrewsDCAppelLJAndersonCAEphraimPLCookCBoulwareLENeighborhood socioeconomic status, race, and mortality in young adult dialysis patientsJournal of the American Society of Nephrology : JASN201425112649265724925723

Baseline Characteristics of National Health and Nutrition Examination Survey (NHANES) III Participants with Chronic Kidney Disease Stages 3 or 4, Overall and by Race/Ethnicity

CharacteristicAll(n=1123)%Non-Hispanic Blacks(n=351)%Non-Hispanic Whites(n=772)%P-value
Mean age in years (SD)73.3 (11.8)68.01 (10.2)74.7 (11.2)0.04
 20-493.96.23.4
 50-7027.448.022.0
 >7068.745.874.6
Male sex42.947.541.80.15
*Poverty Income Ratio<0.0001
 ≤118.140.712.3
 >1 to ≤232.329.932.8
 >2 to ≤319.714.721.0
 >3 to ≤413.79.014.9
 >416.25.619.0
Level of Education<0.0001
 High School or less50.968.846.4
 Some College37.126.639.8
 College or greater11.94.613.8
Diabetes (yes)18.433.314.60.0001
Hypertension (yes)80.489.378.10.001
Estimated GFR, median in ml/min per 1.73m2 (IQR)50.6 (43.9-55.5)50.1 (41.0-55.3)50.8 (44.6-55.5)0.02
Albuminuria (≥30 mg/g)30.4%46.3%26.3%0.03
Total Calories >2000 Kilocalories/day20.8%15.3%22.2%0.06
Potential Renal Acid Load, median in mEq/day (IQR)46.3 (34.7-58.4)50.4 (39.7-66.8)43.9 (32.3-56.0)0.001
Body Mass Index, median in kg/m2 (IQR)27.4 (24.1-30.9)27.8 (25.2-31.6)26.8 (23.9-30.4)0.05
Body Surface Area, median in m2 (IQR)1.86 (1.69-2.04)1.95 (1.71-2.07)1.83 (1.67-1.99)0.05
Net Acid Excretion, median in mEq/day (IQR)46.3 (34.6-58.4)50.9 (40.4-66.8)44.2 (31.9-56.9)0.007

Chronic kidney disease defined using Modification of Diet in Renal Disease study equation to estimate glomerular filtration rate. Poverty income ratio is the ratio of family income to federal poverty threshold. Hypertension was defined by self-report, average systolic blood pressure ≥140 or average diastolic blood pressure ≥90 mmHg, or use of medications. Diabetes was defined by self-report or measured hemoglobin A1c ≥6.5%.

Abbreviations: SD, standard deviation; GFR, glomerular filtration rate; IQR, interquartile range

Hazard Ratios for Chronic Kidney Disease Progression to End Stage Renal Disease (ESRD) Comparing Non-Hispanic Blacks to Non-Hispanic Whites in the National Health and Nutrition Examination Survey (NHANES) III

ModelsBaseline Variables IncludedHazard Ratio (95% Confidence Interval) for ESRD accounting for the competing risk of deathn=1123, ESRD events=248
1Non-Hispanic Blacks versus Non-Hispanic Whites, unadjusted3.35 (2.51-4.48)
2Model 1 + net acid excretion*3.21 (2.40-4.30)
3Model 2 + age, sex3.25 (2.41-4.39)
4Model 3 + poverty income ratio2.62 (1.92-3.58)
5Model 4 + body surface area, total caloric intake, serum bicarbonate, protein intake3.52 (2.55-4.85)
6Model 5 + diabetes, hypertension2.64 (1.90-3.65)
7Model 6 + estimated GFR, urinary albumin-to-creatinine ratio1.68 (1.18-2.38)

Model includes both linear and quadratic terms for net acid excretion.

Abbreviations: GFR, glomerular filtration rate.

Race/Ethnicity Stratified Hazard Ratios for the Association of Net Acid Excretion with Risk of Chronic Kidney Disease Progression to End Stage Renal Disease in the National Health and Nutrition Examination Survey III

Non-Hispanic Blacksn=351, ESRD events=154Hazard Ratio (95% Confidence Interval)per unit (mEq/d) increase in Net Acid ExcretionNon-Hispanic Whitesn=772, ESRD events=94Hazard Ratio (95% Confidence Interval)per unit (mEq/d) increase in Net Acid Excretion
Net Acid Excretion* (unadjusted)1.31 (1.20-1.44)1.02 (0.97-1.06)
+ age, sex1.26 (1.16-1.38)1.03 (0.98-1.08)
+poverty income ratio1.24 (1.17-1.35)1.03 (0.98-1.08)
+body surface area, total caloric intake, serum bicarbonate, protein intake1.20 (1.11-1.30)1.06 (0.99-1.13)
+ diabetes, hypertension1.17 (1.09-1.26)1.04 (0.97-1.12)
+estimated GFR, urinary albumin-to-creatinine ratio1.21 (1.12-1.31)1.08 (0.96-1.20)

Model includes both linear and quadratic terms for net acid excretion.

Abbreviations: GFR, glomerular filtration rate

Baseline Characteristics of National Health and Nutrition Examination Survey (NHANES) III Participants with Chronic Kidney Disease Stages 3 or 4 [Defined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation], Overall and by Race/Ethnicity

CharacteristicAll(n=991)%Non-Hispanic Blacks(n=309)%Non-Hispanic Whites(n=682)%P-value
Mean age in years (SD)73.2 (11.8)67.7 (12.7)74.5 (11.2)0.03
 20-504.06.73.3
 50-7027.548.822.2
 >7068.544.574.5
Male sex42.946.342.00.27
Poverty Income Ratio<0.0001
 <=117.139.611.5
 1-232.229.332.9
 2-319.815.220.9
 3-414.09.815.0
 >416.96.119.6
Education<0.0001
 <High School50.667.846.4
 Some College37.427.339.9
 >College12.05.013.7
Diabetes (yes)18.032.914.30.0001
Hypertension (yes)80.488.478.50.003
Estimated GFR, median in ml/min per 1.73m2 (IQR)47.3 (41.6-55.5)50.2 (41.1-55.2)50.8 (44.5-55.6)0.04
Albuminuria (>30 mg/gm)29.945.126.1<0.0001
Total Calories >2000 Kcal/day21.716.523.10.09
Net Acid Excretion, median in mEq/day (IQR)47.3 (41.6-53.6)47.4 (41.2-52.9)47.2 (41.7-53.8)0.67

CKD-EPI equation was used in sensitivity analysis to define chronic kidney disease, given its reported greater precision over the Modification of Diet in Renal Disease study equations51. Poverty income ratio is the ratio of family income to poverty threshold. Hypertension was defined by self-report, average systolic blood pressure >140 or average diastolic blood pressure >90 mmHg, or use of medication.