Dataset Information

Race, APOL1 Risk, and eGFR Decline in the General Population.

ABSTRACT: The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987-1989 (baseline) to 2011-2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th-90th percentile) unadjusted eGFR decline was 1.5 (1.0-2.2) ml/min per 1.73 m(2) per year for whites, 2.1 (1.4-3.1) ml/min per 1.73 m(2) per year for blacks with APOL1 low-risk status, and 2.3 (1.5-3.5) ml/min per 1.73 m(2) per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.

SUBMITTER: Grams ME

PROVIDER: S-EPMC5004654 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Race, APOL1 Risk, and eGFR Decline in the General Population.

Grams Morgan E ME Rebholz Casey M CM Chen Yuan Y Rawlings Andreea M AM Estrella Michelle M MM Selvin Elizabeth E Appel Lawrence J LJ Tin Adrienne A Coresh Josef J

Journal of the American Society of Nephrology : JASN 20160310 9

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, ...[more]

PMID: 26966015

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Project description:BACKGROUND AND OBJECTIVES:The natural history of kidney disease among blacks who carry the APOL1 high-risk variants varies, with only a subgroup progressing to ESRD. We aimed to determine whether the APOL1 risk variants are associated with incident proteinuria in the context of hypertension-attributed CKD, and whether subsequent kidney function decline after the onset of proteinuria differs by APOL1 risk status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using Cox models, we studied the association between APOL1 risk status and incident proteinuria (defined as a doubling of urine protein-to-creatinine ratio to a level ?0.22 g/g creatinine) among African-American Study of Kidney Disease and Hypertension (AASK) trial participants with APOL1 genotyping and without proteinuria at baseline. RESULTS:Of the 480 participants in our study, 82 (17%) had the high-risk genotypes (2 alleles), and 254 (53%) developed proteinuria over a median follow-up of 6.8 years. At baseline, mean eGFR was lower in the APOL1 high-risk group compared with the low-risk group (0 or 1 allele; 49.6 versus 53.2 ml/min per 1.73 m2, respectively; P=0.02), but median proteinuria was similar (0.04 g/g creatinine for both groups; P=0.43). Individuals with the high-risk genotypes were 1.72-fold more likely to develop incident proteinuria compared with those with the low-risk genotypes (95% confidence interval, 1.27 to 2.32), independent of age, sex, ancestry, baseline eGFR, baseline systolic BP, and randomized treatment groups. Although eGFR declined faster after the onset of proteinuria, this rate did not differ significantly by APOL1 risk status. CONCLUSIONS:Among blacks with established moderate CKD, the APOL1 high-risk variants are associated with greater risk of incident proteinuria. After proteinuria onset, kidney function declines more rapidly but does not differ by APOL1 risk status. This suggests that factors that lead to proteinuria, beyond APOL1, may additionally drive CKD progression.

Project description:BACKGROUND:Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. METHODS:In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. RESULTS:In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). CONCLUSIONS:Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Project description:Background/objectivesAPOL1 high-risk genotypes confer an increased risk for kidney disease, but their clinical significance among older adults remains unclear. We aimed to determine whether APOL1 genotype status (high risk = 2 risk alleles; low risk = 0-1 risk alleles) and self-reported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality among older adults participating in a community-based cohort study.DesignObservational longitudinal cohort study.SettingThe Atherosclerosis Risk in Communities (ARIC) study.ParticipantsCommunity-dwelling older adults (mean age = 75.8 years; range = 66-90 years).ResultsAmong 5,564 ARIC participants (78.2% White, 19.1% APOL1 low-risk Black, and 2.7% APOL1 high-risk Black), the proportion with creatinine and cystatin C-based estimated glomerular filtration rate (eGFRCrCys ) below 60 mL/min/1.73 m2 at baseline was 40.6%, 34.8%, and 43.2%, respectively. Over a mean follow-up of 5.1 years, APOL1 high-risk Blacks had a 2.67-fold higher risk for ESRD compared with low-risk Blacks (95% confidence interval [CI] = 1.05-6.79) in models adjusted for age and sex. This association was no longer significant upon further adjustment for baseline eGFRCrCys and albuminuria (hazard ratio [HR] = 1.08; 95% CI = .39-2.96). Rate of hospitalizations and risks of mortality and incident CKD did not differ significantly by APOL1 genotype status. Compared with Whites, Blacks had 1.85-fold and 3.45-fold higher risks for incident CKD and ESRD, respectively, in models adjusted for age, sex, eGFRCrCys , and albuminuria. These associations persisted after additional adjustments for clinical/socioeconomic factors and APOL1 genotype (incident CKD: HR = 1.38; 95% CI = 1.06-1.81; ESRD: HR = 3.20; 95% CI = 1.16-8.86).ConclusionAmong older Black adults, APOL1 high-risk genotypes were associated with lower kidney function and therefore higher risk of ESRD. Racial disparities in incident kidney disease persisted in older age and were not fully explained by APOL1.

Dataset Information

Race, APOL1 Risk, and eGFR Decline in the General Population.

Publications

Race, APOL1 Risk, and eGFR Decline in the General Population.

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