937 - Impact of Donor APOL1 Variants on Long-Term Graft Survival in Living Kidney Transplantation: Interim Analysis of the BRIDGES-APOL1 Study

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Author Block: M. G. Tavares¹, L. Ferreira², G. D. Ferreira³, L. Godoi³, M. Soares³, R. Lima³, R. Finamor³, R. Demarchi Foresto², J. Medina-Pestana², L. Requião-Moura⁴, ¹Hospital do Rim – Fundação Oswaldo Ramos, São Paulo, Brazil, ²Hospital do Rim – Fundação Oswaldo Ramos, Sao Paulo, Brazil, ³Universidade Federal de São Paulo, Sao Paulo, Brazil, ⁴Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
*Purpose: To evaluate the frequency of high-risk APOL1 variants among living kidney donors and to assess the impact of these variants on long-term graft survival in recipients.
*Methods: This is an interim analysis of the BRIDGES-APOL1 study, a historical cohort including 1,225 living donor-recipient kidney transplant pairs who underwent transplantation between 2008 and 2015, with a minimum follow-up of 10 years post-transplant. This report presents data from the first 539 pairs (44%). APOL1 genotyping was performed using Sanger sequencing. Recipients were stratified according to the presence of donor APOL1 risk variants: G0/G0 vs. ≥1 variant (G0/G1, G0/G2, G1/G1, G1/G2, or G2/G2). Graft survival was estimated using the Kaplan-Meier method, and multivariable analysis was performed using Cox proportional hazards regression.
*Results: Overall, 16.8% of donors carried at least one APOL1 risk variant: 11.1% G0/G1, 4.5% G0/G2, 1.2% G1/G2, and no G2/G2 cases were identified. Among G0/G0 donors, 62.1% self-identified as White and 37.9% as Afro-Brazilian (p = 0.01). Donors had a mean age of 45.4 years, 62% were female, and 53.2% were siblings of their recipients. Apart from ethnicity, no other demographic differences were observed between G0/G0 vs. ≥1 variant. Recipients whose donors carried ≥1 APOL1 variant were more frequently Afro-Brazilian (62.6% vs. 47.3%, p = 0.008) and less likely to have received a preemptive transplant (7.7% vs. 16.7%, p = 0.03). Induction therapy with thymoglobulin or basiliximab was used in 31.9% of recipients. Maintenance immunosuppression predominantly included a calcineurin inhibitor combined with azathioprine (69.8%), with no significant differences between groups. At 10 years, death non-censored graft survival was 88.3% among recipients of G0/G0 donor kidneys and 81.7% among those with donors carrying ≥1 variant (HR = 1.622; 95% CI = 1.003-2.624; p = 0.049). In the multivariable analysis, time on dialysis before transplantation (HR per year = 1.076; 95% CI = 1.003-1.156; p = 0.042) and the presence of ≥1 APOL1 variant (HR = 1.635; 95% CI = 1.011-2.664; p = 0.045) were independently associated with death-uncensored graft loss.
*Conclusions: The prevalence of risk variants was consistent with previous studies involving relatives of dialysis patients. The presence of at least one APOL1 risk variant independently increased the long-term risk of graft loss by 63%, highlighting the potential clinical relevance of donor genetic screening in kidney transplantation.