<i>APOL1</i> Risk Variants, Race, and Progression of Chronic Kidney Disease

TLDR

Black patients with chronic kidney disease in the United States have a higher risk of progressing to end‑stage renal disease than white patients. This study investigates how APOL1 risk variants influence chronic kidney disease progression. The authors analyzed 693 black patients in the AASK trial and 2,955 white and black patients in the CRIC cohort, comparing outcomes between those with two high‑risk APOL1 alleles and those with zero or one allele. Patients with two high‑risk APOL1 alleles experienced a higher rate of kidney failure—hazard ratio 1.88 in AASK and accelerated eGFR decline and composite outcomes in CRIC—indicating that APOL1 variants drive the greater progression seen in black patients regardless of diabetes status. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and other agencies.

Abstract

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.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.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).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.).