Association of Collapsing Glomerulopathy with Donor APOL1 Risk Variants in Kidney Allografts from Black Donors

Introduction: Collapsing glomerulopathy (CG) in the kidney allograft is an infrequent complication, encountered more often in recipients of kidneys from Black donors. Despite its poor prognosis, the genetic susceptibility of this complication remains incompletely understood. Methods: We performed a retrospective study from two major North American transplant centers. We assessed 47 recipients of kidney allografts from Black donors that developed CG and were followed for a median of 2.9 years after transplantation. Donor APOL1 genotypes were available in 44 patients with CG and compared to 560 recipients of kidneys from Black donors who did not develop CG. Results: Transplant recipients with CG were 55% of Black race and 40% female, and CG developed at a median 9.5 of months post-transplantation. Donors harboring zero, one, and two APOL1 kidney-risk variants (KRVs) comprised 16%, 41%, and 43% of CG cases and 45%, 43%, and 12% of controls, respectively. Combining cases and controls, receipt of a kidney from donors with two KRVs was associated with a higher risk of CG compared to donors with zero KRVs [adjusted odds ratio=12.51 (95% confidence interval: 4.83 – 32.39), P<0.001 ]. Receipt of a kidney with one KRV was also associated with a higher risk of CG compared to donors with no KRVs, although with lower effect than those with two KRVs [adjusted odds ratio=3.39 (1.36 – 8.46), P=0.009 ]. Recipients of kidneys from donors with two KRVs, but not with one KRV, had lower graft survival when compared to donors with zero KRVs [adjusted hazard ratio=1.49 (1.03 – 2.16), P=0.04 ]. Conclusions: While the association of CG in the kidney allograft with donor APOL1 KRVs suggests possible dose-dependent effects, lower graft survival was only observed in recipients of kidneys with two KRVs. Identification of additional risk factors for CG may improve utilization of kidneys from Black donors, including these with APOL1 KRVs.