Dataset Information

APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension).

ABSTRACT: OBJECTIVE:Among African Americans, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease. APPROACH AND RESULTS:In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with APOL1 genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m2) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between APOL1 genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, APOL1 high-risk variants were associated with increased cardiovascular mortality. CONCLUSIONS:Among African Americans with hypertension-attributed chronic kidney disease, APOL1 risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.

SUBMITTER: Chen TK

PROVIDER: S-EPMC5570668 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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<i>APOL1</i> Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension).

Chen Teresa K TK Appel Lawrence J LJ Grams Morgan E ME Tin Adrienne A Choi Michael J MJ Lipkowitz Michael S MS Winkler Cheryl A CA Estrella Michelle M MM

Arteriosclerosis, thrombosis, and vascular biology 20170601 9

<h4>Objective</h4>Among African Americans, the apolipoprotein L1 (<i>APOL1</i>) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease.<h4>Approach and results</h4>In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate t ...[more]

PMID: 28572159

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Project description:BackgroundAnemia is common in chronic kidney disease (CKD) and associated with poor outcomes. In cross-sectional studies, lower estimated glomerular filtration rate (eGFR) has been associated with increased risk for anemia. The aim of this study was to determine how hematocrit changes as eGFR declines and what factors impact this longitudinal association.MethodsWe followed 1094 African-Americans with hypertensive nephropathy who participated in the African-American Study of Kidney Disease and Hypertension. Mixed effects models were used to determine longitudinal change in hematocrit as a function of eGFR. Interaction terms were used to assess for differential effects of age, gender, baseline eGFR, baseline proteinuria, malnutrition and inflammation on eGFR-associated declines in hematocrit. In sensitivity analyses, models were run using iGFR (by renal clearance of I(125) iothalamate) in place of eGFR.ResultsAt baseline, mean hematocrit was 39% and 441 (40%) individuals had anemia. The longitudinal relationship between eGFR and hematocrit differed by baseline eGFR and was steeper when baseline eGFR was <45 mL/min/1.73 m(2). For example, the absolute decline in hematocrit per 10 mL/min/1.73 m(2) decline in longitudinal eGFR was -3.7, -1.3 and -0.5% for baseline eGFR values of 20, 40 and 60 mL/min/1.73 m(2), respectively (P < 0.001 comparing the longitudinal association between baseline eGFR = 40 or 60 versus baseline eGFR = 20 mL/min/1.73 m(2)). Similarly, male sex, younger age (<65 years) and higher baseline proteinuria (protein-to-creatinine ratio >0.22) were associated with greater hematocrit declines per unit decrease in longitudinal eGFR compared with female sex, older age and low baseline proteinuria, respectively (P-interaction <0.05 for each comparison). The longitudinal eGFR-hematocrit association did not differ by body mass index, serum albumin or C-reactive protein.ConclusionsMen, younger individuals and those with low baseline eGFR (<45 mL/min/1.73 m(2)) or baseline proteinuria are particularly at risk for eGFR-related declines in hematocrit.

Project description:Rationale & objectivePatients with a high-risk Apolipoprotein L1 (APOL1) genotype are more likely to develop chronic kidney disease and kidney failure. It is unclear whether this increased risk is entirely mediated by the development of proteinuria.Study designRetrospective observational study of the African American Study of Kidney Disease and Hypertension cohort and Chronic Renal Insufficiency Cohort.Exposures & predictorsSelf-identified race (Black/non-Black) and presence of high-risk APOL1 genotype. The primary model was adjusted for age, sex, diabetes, estimated glomerular filtration rate, and urinary protein-creatinine ratio.OutcomesTime to kidney failure defined as time to dialysis or transplantation.Analytical approachWe used Cox proportional hazard models to study how proteinuria mediates the association between APOL1 and kidney failure. We modeled proteinuria at baseline and as a time-varying covariate.ResultsA high-risk APOL1 genotype was associated with a significantly higher risk of kidney failure, even for patients with minimal proteinuria (HR, 1.87; 95% CI, 1.23-2.84). The association was not significant among patients with high proteinuria (HR, 1.22; 95% CI, 0.93-1.61). When modeling proteinuria as a time-varying covariate, a high-risk APOL1 genotype was associated with higher kidney failure risk even among patients who never developed proteinuria (HR, 2.04; 95% CI, 1.10-3.77). Compared to non-Black patients, Black patients without the high-risk genotype did not have higher risk of kidney failure (HR, 0.96; 95% CI, 0.85-1.10).LimitationsTwo datasets were combined to increase statistical power. Limited generalizability beyond the study cohorts. Residual confounding common to observational studies.ConclusionsA high-risk APOL1 genotype is significantly associated with increased kidney failure risk, especially among patients without baseline proteinuria. Although our results suggest that the risk is partially mediated through proteinuria, higher kidney failure risk was present even among patients who never developed proteinuria. Providers should consider screening for the high-risk APOL1 genotype, especially among Black patients without proteinuria in populations with chronic kidney disease.

Project description:Background and objectivesTrajectories of eGFR in patients with CKD are highly variable. Only a subset of patients with CKD experiences a steady decline in eGFR. The objective of our study was to investigate whether eGFR trajectory patterns differ by APOL1 risk status.Design, setting, participants, & measurementsOur study was a longitudinal observational study of 622 participants in the African American Study of Kidney Disease and Hypertension with APOL1 genotyping and sufficient follow-up for estimating GFR trajectories. The predictor was APOL1 high-risk status (having two copies of the G1 or G2 risk alleles) versus low-risk status (zero or one copy of the risk alleles), and the outcome was four eGFR trajectory patterns on the basis of the joint probabilities of linearity and progression: steady decline, unsteady decline, steady stable, and unsteady stable.ResultsOver a median follow-up of 9 years, 24.0% of participants experienced steady eGFR decline, 25.9% had an unsteady decline, 25.6% were steady and stable, and 24.6% were unsteady but stable. Those experiencing steady decline had lower eGFR and higher urine protein-to-creatinine ratio at baseline than participants with the other eGFR trajectory patterns. The APOL1 high-risk group was associated with a greater odds for the steady decline pattern than the APOL1 low-risk group (unadjusted odds ratio, 2.45; 95% confidence interval, 1.62 to 3.69). This association remained significant after adjusting for demographic factors, baseline eGFR, urine protein-to-creatinine ratio, treatment assignment, and follow-up time (adjusted odds ratio, 1.59; 95% confidence interval, 1.00 to 2.52).ConclusionsAmong patients with CKD attributed to hypertension, those with the APOL1 high-risk genotype were more likely to experience a steady decline trajectory in eGFR than those without the APOL1 high-risk genotype. These findings suggest a persistent underlying pathophysiologic process in those patients with the APOL1 high-risk genotype.

Dataset Information

APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension).

Publications

<i>APOL1</i> Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension).

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