BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by excessive oxalate production that leads to nephrocalcinosis or nephrolithiasis and progressive kidney failure, associated with systemic oxalosis that is not reversed by dialysis. Pharmacological treatment is limited. Combined or sequential liver and kidney transplant is standard of care for PH1. Recently approved RNA-interference (RNAi) therapy with lumasiran or nedosiran targeting glycolate oxidase and lactate dehydrogenase A, respectively, reduces hepatic oxalate synthesis. This makes kidney-only (isolated) transplantation (iKT) a potentially successful, novel approach for managing PH1 patients with advanced kidney disease combined with hyperhydration, urine alkalinization, and vitamin B6 (where applicable). METHODS: We analyzed the course of a young PH1 kidney transplant recipient at our institution and performed a literature review of patients with small interfering RNA-enabled iKT. CASE PRESENTATION: A patient with PH1 due to a homozygous, pathogenic variant in AGXT exon 1 (c.121G>A; p.Gly41Arg) received a deceased donor kidney transplant after 6.5 years of hemodialysis and 4.3 years of RNAi therapy with lumasiran. He maintained good kidney allograft function 9 months post-transplant despite the occurrence of an asymptomatic calyceal stone within the graft prior to transition to adult nephrology care. At 14 months, he experienced a T cell-mediated rejection, associated with a rise in serum creatinine and plasma oxalate, and a partially obstructing stone. A review of all 10 accessible cases of RNAi-supported iKT, including our own, revealed several instances of kidney stone formation (20%), stent obstruction (20%), and mild, mostly transient crystal deposition in the graft (37.5%). CONCLUSIONS: This report enriches the limited experience of RNAi-enabled kidney-only transplantation in PH1. RNA interference therapy has the potential to challenge the current standard of dual liver and kidney transplantation in children and young adults with this devastating disease but requires uninterrupted access to the drug with individualized, eGFR and oxalate level adjusted dosing, continued vigilance, and reporting of long-term outcomes.
Habeeb et al. (Fri,) studied this question.