Premium
Podocyte density is reduced in kidney allografts with high‐risk APOL1 genotypes at transplantation
Author(s) -
Chen Dhruti P.,
Zaky Ziad S.,
Schold Jesse D.,
Herlitz Leal C.,
ElRifai Rasha,
Drawz Paul E.,
Bruggeman Leslie A.,
Barisoni Laura,
Hogan Susan L,
Hu Yichun,
O’Toole John F.,
Poggio Emilio D.,
Sedor John R.
Publication year - 2021
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.14234
Subject(s) - medicine , hazard ratio , podocyte , kidney , kidney transplantation , urology , genotype , proportional hazards model , transplantation , glomerulosclerosis , endocrinology , gastroenterology , proteinuria , confidence interval , gene , biology , genetics
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/10 6 um 3 , 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 48 months. More rapid eGFR decline was seen in recipients of high‐risk APOL1 allografts ( P < .001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min 2 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.