APOL1 Genotype and Renal Function of Black Living Donors

Abstract

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m²; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m²; P=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m² per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.

Keywords: human genetics; kidney donation; renal function.

Graphical abstract

Figure 1.

Lower pre- and post-donation eGFR in donors with high-risk APOL1 genotype than low-risk APOL1 genotype. Part A shows that the predonation and postdonation eGFRs were lower in donors carrying two APOL1 renal risk alleles (or high-risk genotype) than those carrying zero or one APOL1 renal risk allele (or low-risk genotype). Part B shows that a greater fraction of donors with two APOL1 renal risk alleles (high-risk genotype) had postdonation eGFR<60 ml/min per 1.73 m². eGFR was calculated via the CKD-EPI formula.

Figure 2.

Rate of decline in postdonation eGFR is greater among donors with high-risk versus low-risk APOL1 genotype. Serum creatinine values spanning the period from 12 months after donation (to allow for renal compensation) to last follow-up were abstracted on all participating donors. eGFR was calculated at each of the time points via the CKD-EPI formula using serum creatinine and age of the donor at these time points. A shows that the donors carrying two APOL1 renal risk alleles (or high-risk genotype) had faster decline in postdonation eGFR than those carrying zero or one APOL1 renal risk allele (or low-risk genotype). B shows the postdonation eGFR trajectory on 19 APOL1 high-risk genotype donors.

Figure 3.

Similar rate of decline in eGFR between donors and matched nondonors grouped by APOL1 genotype. eGFR was calculated for donors and nondonors via the CKD-EPI formula from serum creatinine values spanning the period from 12 months postdonation (to allow for renal compensation in the donors) and at the subsequent examination year, which is at every 5 years (for nondonors), to the last follow-up. There was no difference in change in eGFR between donors and nondonors stratified by APOL1 renal risk status. A depicts comparison of eGFR between donors and nondonors with zero or one APOL1 renal risk allele (low-risk genotype), and B depicts comparison of eGFR between donors and nondonors with two APOL1 renal risk alleles (high-risk genotype).