APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease

Abstract

Relative to European Americans, evidence supports that African Americans with end-stage renal disease (ESRD) survive longer on dialysis. Renal-risk variants in the apolipoprotein L1 gene (APOL1), associated with non-diabetic nephropathy and less subclinical atherosclerosis, may contribute to dialysis outcomes. Here, APOL1 renal-risk variants were assessed for association with dialytic survival in 450 diabetic and 275 non-diabetic African American hemodialysis patients from Wake Forest and Emory School of Medicine outpatient facilities. Outcomes were provided by the ESRD Network 6-Southeastern Kidney Council Standardized Information Management System. Dates of death, receipt of a kidney transplant, and loss to follow-up were recorded. Outcomes were censored at the date of transplantation or through July 1, 2015. Multivariable Cox proportional hazards models were computed separately in patients with non-diabetic and diabetic ESRD, adjusting for the covariates age, gender, comorbidities, ancestry, and presence of an arteriovenous fistula or graft at dialysis initiation. In non-diabetic ESRD, patients with two (vs. zero/one) APOL1 renal-risk variants had significantly longer dialysis survival (hazard ratio 0.57); a pattern not observed in patients with diabetes-associated ESRD (hazard ratio 1.29). Thus, two APOL1 renal-risk variants are associated with longer dialysis survival in African Americans without diabetes, potentially relating to presence of renal-limited disease or less atherosclerosis.

Survival Advantage of African American Dialysis Patients with End-Stage Renal Disease Causes Related to APOL1

“…These results extend the work of Ma et al [15] who made a similar observation, namely that APOL1 high risk genotypes are associated with longer hemodialysis survival in nondiabetic subjects ( n = 275, HR 0.57) but not in diabetic subjects ( n = 450, HR 1.29). In our study, which lacks APOL1 genotype data but has larger sample sizes, the AA survival advantage was observed in the APOL1 -associated nephropathy group including ESRD attributed to DM, hypertension, and APOL1-enriched GN.…”

“…APOL1 risk variants have been associated with progression to ESRD regardless of diabetes status [19]. However, Ma et al [15]found that APOL1 risk variants have been associated with longer hemodialysis survival only in nondiabetic AA patients. Hypertension-attributed ESRD (histologically likely to be arterionephrosclerosis) in AA is associated with APOL1 variants (OR 4.6 [20]).…”

“…Studies on the effect of APOL1 renal risk variants on cardiovascular disease (CVD) and death showed conflicting results [10]. Some studies reported the association between APOL1 renal risk variants and higher risk for CVD events and mortality [11, 12], whereas others observed the protective relationship between APOL1 renal risk variants and development of subclinical CVD, cerebrovascular disease, and death [13-15]. We hypothesized that AA have better survival than European Americans among dialysis patients with ESRD causes associated with APOL1 .…”

<b><i>APOL1</i></b> and Mortality in Patients on Dialysis

“…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]. …”

Strict blood pressure control associates with decreased mortality risk by APOL1 genotype

“…20, 21 Some studies have found a higher risk of atherosclerotic disease in individuals with APOL1 high-risk genotype, although this finding has not been consistent across all studies. 21-23 Since cardiovascular disease is the leading cause of mortality in patients with CKD, it is plausible that APOL1 status may associate with a differential risk of death. For example, one recent study demonstrated a 30% excess mortality risk in older blacks with the high- versus low-risk APOL1 genotype.…”