APOL1 and Mortality in Patients on Dialysis

Abstract

Ancestry-based disparities in medical outcomes are widely appreciated. In this issue of Cardiorenal Medicine, Lertdumrongluk et al. [1] assess mortality based on ancestry and reported the cause of end-stage kidney disease (ESKD) in patients treated at a large dialysis organization. As expected, African Americans had a significantly lower mortality rate than European Americans; the largest differences in mortality in favor of African Americans were in patients felt likeliest to have apolipoprotein L1 gene (APOL1)-associated kidney diseases. These included patients with idiopathic focal segmental glomerulosclerosis, histologically not-examined glomerular diseases presumably attributed to hypertension and/or arterionephrosclerosis (e.g., solidified glomerulosclerosis), lupus nephritis, and nephropathy due to illicit drug use. A strength of this work was the large sample size; a weakness that APOL1 genotyping was not performed. The authors estimated APOL1 genotype frequencies based upon reported causes of ESKD and these may be inaccurate [2]. Results confirmed those from a prior report where African Americans with APOL1 high-risk genotypes (G1G1, G2G2 and G1G2) had lower mortality than African Americans with low-risk genotypes and European Americans, a work that included APOL1 genotyping in a smaller cohort [3]. In the general population, African Americans experience higher mortality rates from cardiovascular disease (CVD), and at younger ages, than European Americans. Unfortunately, this results in a 3.4 years’ shorter average life expectancy. In contrast, African Americans with dialysis-dependent ESKD have 45% lower mortality than European Americans, regardless of dialysis modality (in-center hemodialysis, home hemodialysis or peritoneal dialysis) and after adjustment for comorbid illnesses, biochemical factors and health-related quality of life. This “paradoxical” survival advantage in African Americans with ESKD is reproducibly observed despite disparities in income and residential segregation [4]. Lower mortality in African Americans with ESKD, relative to European Americans, could coincide with improved access to healthcare; the Centers for Medicare and Medicaid Services support dialysis costs for many patients in the US. Outcomes in patients with ESKD appear consistent with those at Received: May 30, 2019 Accepted: June 4, 2019 Published online: June 11, 2019