Introduction:
Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by hepatic oxalate overproduction leading to progression to chronic kidney disease (CKD). Lumasiran is the first RNA interference (RNAi) therapy that reduces hepatic oxalate production, administered to patients with PH1. The aim of the study was to evaluate lumasiran efficacy and kidney outcome in children with PH1.
Methods:
Four children (2M/2F), including 2 siblings with genetically confirmed PH1 treated with subcutaneous (sc) lumasiran at a dose of 3 mg/kg (n=3) and 6 mg/kg (n=1) were included to the single-center prospective study. The median follow-up was 9.5 (IQR: 6.0; 23.5) months.
Results:
Children with PH1 presented with nephrocalcinosis and urolithiasis (n=2) and one patient each had nephrocalcinosis and urolithiasis. Pathogenic compound heterozygous AGXT variants were identified in 2 siblings: c.121G>A (p.Gly41Arg); c.508G>A (p.Gly170Arg) and one patient each had homozygous AGXT variants: c.1020A>G (p.Ile340Met) and c.508G>A (p.Gly170Arg). The indication for lumasiran therapy was a decrease in eGFR on pyridoxin to CKD-2 (n=2), CKD-3a (n=1) and CKD-3b (n=1). The median age of children at start of lumasiran was 10.3 (IQR: 6.3; 16.0) years. The number of sc injections varied from 4 to 10 at the last follow-up. The median baseline urinary oxalate level was 0.94 (IQR: 0.66; 1.56) mmol/1.73 m2/day. The mean reduction of urinary oxalate level from baseline to the last follow-up was 78.8%. The median eGFR at the last follow up did not differ significant from baseline level: 62.4 (IQR: 42.1; 73.0) vs. 61.0 (IQR: 40.4; 77.7) ml/min/1.73 m2 (p=0.875). Lumasiran-related adverse effects included mild injection site reactions (hyperemia, transient pain, muscle twitching).
Conclusions:
Lumasiran showed sustained urinary oxalate reductions in PH1 children with CKD 2-3b with stable eGFR level and acceptable safety profile. Prescribing RNAi treatment to PH1 children at an earlier age could prevent a decline in kidney function.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.