Collapsing FSGS in a kidney transplant with a single APOL1 risk variant: a case report

Apolipoprotein L1 (APOL1) genetic risk variants substantially increase the risk of chronic kidney disease and kidney failure among individuals of recent African ancestry. While APOL1-associated nephropathy was long considered to follow a recessive inheritance pattern, recent studies have demonstrated an additive effect, indicating that even a single risk variant may be clinically significant. A severe manifestation of APOL1-mediated kidney disease, collapsing focal segmental glomerular sclerosis, has been reported mainly in allografts from donors with two risk variants. A 60-year-old Surinamese woman of West-African descent with end-stage kidney disease of unknown origin received a kidney transplant from her daughter, with pre-existing donor-specific Class II antibodies detected. The patient experienced delayed graft function, active antibody-mediated rejection, and ultimately developed collapsing focal segmental glomerular sclerosis. Despite intensive treatment, the graft failed, necessitating transplantectomy. Genetic testing revealed a G1G1 APOL1 genotype in the recipient and G1G0 in the donor. This case suggests that both donor and recipient APOL1 genotypes can contribute to the development of APOL1-mediated kidney disease post-transplantation, and highlights the potential risk associated with even a single APOL1 risk variant in the donor as well as the possible role of the recipient’s APOL1 genotype affecting the immune system. These observations support the consideration of routine APOL1 genotyping in donors of West-African ancestry to improve transplant safety and risk assessment.