Podocyte density is reduced in kidney allografts with high-risk APOL1 genotypes at transplantation.

Abstract

Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n=107) were genotyped for APOL1 variants. To determine whether allografts from high-risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high-risk and low-risk genotypes. Demographic characteristics were similar in high-risk (n=16) and low-risk (n=91) donors. Podocyte density was significantly lower in high-risk than low-risk donors (108±26 vs 127±40 podocytes/106 um3 , P=.03). Kaplan-Meier graft survival (high-risk 61% vs. low-risk 91%, p-value=0.049) and multivariable Cox models (hazard ratio=2.6; 95% CI, 0.9-7.8) revealed higher graft loss in recipients of APOL1 high-risk allografts over 48months. More rapid eGFR decline was seen in recipients of high-risk APOL1 allografts (P<.001). At 60months, eGFR was 27 vs. 51mL/min/1.73min2 in recipients of APOL1 high-risk vs low-risk kidney allografts, respectively. Kidneys from high-risk APOL1 donors had worse outcomes versus low-risk APOL1 genotypes. Lower podocyte density in kidneys from high-risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors.