Long-term transplantation outcomes in patients with Primary Hyperoxaluria Type 1 included in the European Hyperoxaluria Consortium (OxalEurope) Registry

Abstract Introduction In primary hyperoxaluria type 1 (PH1) oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver-kidney transplantation has been recommended in patients with kidney failure. However, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation for patients with vitamin B6-responsive genotypes. Methods We used the OxalEurope registry for retrospective analyses of PH1 patients who underwent transplantation. Crude Kaplan-Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed. Results A total of 267 PH1 patients underwent transplantation between 1978 and 2019. Data of 244 patients (159 combined liver-kidney transplantations, 48 isolated kidney transplantations, 37 sequential liver-kidney transplantations) were eligible for comparative analyses. Comparing combined liver-kidney transplantations to isolated kidney transplantations, adjusted mortality was similar in patients with B6-unresponsive genotypes, but lower following isolated kidney transplantation in patients with B6-responsive genotypes (aHR 0.07 95%CI 0.01-0.75, P= 0.028). Combined liver-kidney transplantation yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P=0.025, P Conclusion Combined or sequential liver-kidney transplantation remains the preferred transplantation modality in PH1 patients with B6-unresponsive genotypes, but isolated kidney transplantation could be an alternative approach in patients with B6-responsive genotypes.