RNA interference medication and transplantation procedures in patients with primary hyperoxaluria type 1

ABSTRACT Background and hypothesis Defective hepatic alanine-glyoxylate aminotransferase (AGT) leads to oxalate overproduction in primary hyperoxaluria type 1 (PH1). Nedosiran and lumasiran are RNA interference (RNAi) agents inhibiting oxalate production. In PH1 patients with kidney failure, isolated kidney transplantation (iKTx) might be possible with RNAi medication. Methods We report on 17 PH1 patients on hemodialysis, who received lumasiran (7 patients, 1–68 years, 6 females), lumasiran post-nedosiran (2 patients, both 6.5 years, male), double RNAi (dRNAi) (4 patients, 37 years, 3 infants, all male) and nedosiran (4 patients, 11–58 years, 2 female). Plasma oxalate (Pox) pre-HD was measured and systemic oxalate grading (SOG) was evaluated mainly by bone magnetic resonance imaging and speckle echocardiography, before the start of and repeatedly during treatment. Results In four patients iKTx was performed, being successful or with recurrence in two patients each. In others, development of Pox values under RNAi treatment and thus SOG increment and clinical deterioration were profound arguments for transplant decisions. Based on that, iKTx is now planned in five and liver/kidney Tx in four patients (one liver already transplanted). Three patients have died. Conclusion Pox should not be the sole parameter by which to decide on Tx procedure. In patients with minor oxalate deposition, no SOG deterioration and sensitivity to vitamin B6 or under efficacious RNAi treatment, iKTx can be considered. Severe (and deteriorating) systemic oxalosis, high Pox during RNAi treatment and maximum dialysis should lead to reconsidering combined or sequential LKTx rather than iKTx. Patients with severe systemic oxalosis at time of diagnosis still have a high mortality rate.