Professor of Pediatrics UPMC Childrens Hospital of Pittsburgh Pittsburgh, Pennsylvania, United States
Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, resulting nephrocalcinosis, kidney stones, kidney failure and systemic oxalosis. Lumasiran is a liver-directed RNA interference therapeutic agent which was FDA approved November 2020 for the treatment of PH1. It reduces hepatic oxalate production by targeting glycolate oxidase and dramatically reduces oxalate excretion Objective: To describe clinical outcomes with lumasiran in clinical practice Design/Methods: A retrospective single center study of non-ESKD patients with a genetic diagnosis of PH1 treated with lumasiran. Data were collected regarding demographics, clinical characteristics, treatments, biochemistries, 24 hour oxalate excretion, urological surgeries (Surg), kidney stone events requiring emergency department visits or hospitalization, and radiological evidence of nephrocalcinosis (NC) were collected pre-and-post start of lumasiran treatments (Tx). The patient perspective was also assessed. Results: Four male pediatric patients with PH1 were treated with lumasiran at ages 1- 11yrs. Three presented with kidney stones of which one had severe AKI. One was an asymptomatic twin. All had nephrocalcinosis prior to treatment. One patient presenting 7 years prior to lumasiran treatment had 8 kidney stone events and 2 surgeries. Post treatment all patients had no further kidney stone events or surgeries, eGFR remained stable or improved, nephrocalcinosis resolved on imaging, and 24-hour urine oxalate decreased by >50% (Table). Patients tolerated the treatment well and found the therapy highly efficacious.
Conclusion(s): PH1 is heterogenous disease with a spectrum of age and clinical presentation. Lumasiran resulted in a significant improvement in clinical, radiological, and biochemical outcomes, and had high patient satisfaction.
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