Insufficient Inhibition of Oxalate Production by Lumasiran in an Adult With Kidney Failure due to Primary Hyperoxaluria Type 1: A Case Report

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by endogenous overproduction of oxalate, which leads to kidney failure in over 60% of patients. Lumasiran is an RNAi-based therapy with promising results in PH1 patients. Case reports suggest it may even serve as a substitute for liver transplantation in PH1 patients with chronic kidney disease (CKD) stages 5-5D. Here, we present a PH1 patient with severe systemic oxalosis and dependent on dialysis who was started on lumasiran. Although lumasiran brought symptom relief of his systemic oxalosis, it did not reduce plasma oxalate to levels deemed sufficient to safely perform kidney transplantation only. A liver transplantation was therefore performed, after which plasma oxalate levels decreased further. Six months after liver transplantation the patient underwent a successful kidney transplantation. This case demonstrates good, but insufficient inhibition of endogenous oxalate production by lumasiran, raising important considerations for management of PH1 in patients with advanced CKD. Furthermore, it suggests that even in case of incomplete blockade of oxalate overproduction, lumasiran may serve as bridge therapy to combined liver-kidney transplantation, as it may stop further development of systemic oxalosis and reduce the risk of kidney graft failure due to oxalate nephropathy.