Abstract / Summary
Introduction Primary hyperoxaluria type 1 (PH1) is a rare genetic disease causing severe hyperoxaluria, kidney stones, nephrocalcinosis, and progressive kidney failure (KF) followed by systemic oxalosis. Expert guidelines traditionally recommended liver-kidney transplantation (LKTx) for PH1 patients with KF unresponsive to vitamin B6, with 1-year mortality of 5-15%. Small-interfering ribonucleic acid (siRNA) therapies targeting hepatic oxalate production have shifted the treatment landscape. Eighteen patients on siRNA therapy with successful kidney-alone transplant (KATx) have been reported. Methods A multicenter retrospective case series across international centers from 11 countries included patients with: (1) confirmed PH1 diagnosis; (2) KATx as definitive kidney replacement therapy; and (3) concurrent lumasiran and/or nedosiran treatment beyond the induction phase before and/or after transplant. Results Thirty-eight patients were analyzed: at transplant, 27 received lumasiran, 6 nedosiran, and 1 both ; 60.5% carried a priori B6-responsive variants. All 25 AGXT alleles identified were pathogenic or likely pathogenic, including three not previously reported in PH1 and one requiring haplotype-level resolution. Median pre-transplant plasma oxalate was 59 μmol/L (IQR 30, range 5-100). Donors were deceased in 57.9%; 39.5% of recipients were pediatric. Median follow-up was 25 months (range 2-60). Peri-/post-transplant dialysis was used in 60.5%. Four patients diagnosed post-KATx were included; three were successfully treated with lumasiran. One-year graft survival was 95%; patient survival was 100%. Conclusions This large international series supports KATx as standard of care for carefully selected PH1 patients with assured long-term siRNA therapy and expert follow-up. Practical recommendations, including a peri-transplant checklist emphasizing expert-centered care and vigilance for emerging complications, are provided.