Conference Coverage

Lumasiran Improves Kidney Survival in Patients with Primary Hyperoxaluria Type 1, Showing 95% Reduction in Risk of End-Stage Kidney Disease

Anthony Calabro, MA

Key Highlights

  • Patients with primary hyperoxaluria type 1 who were treated with lumasiran experienced no cases of end-stage kidney disease (ESKD) during follow-up.
  • Patients in the historical control group had an ESKD-free survival rate of 88% at 4 years, compared with 100% in the lumasiran-treated group.
  • Lumasiran was associated with a 95% reduction in the hazard of developing ESKD.

Lumasiran therapy demonstrated sustained efficacy in patients with primary hyperoxaluria type 1 (PH1), maintaining stable kidney function over several years and supporting improved outcomes after isolated kidney transplantation. Across Phase 2 and 3 studies, patients receiving lumasiran exhibited minimal declines in eGFR and consistent reductions in plasma oxalate, a major driver of disease progression. This study was presented at Kidney Week 2025 in Houston, TX.

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by hepatic oxalate overproduction leading to progressive kidney damage and an increased risk of end-stage kidney disease (ESKD). Despite conventional management strategies such as high fluid intake, crystal inhibitors, and pyridoxine supplementation, many patients still progress to renal failure. Lumasiran, a small interfering RNA (siRNA) therapeutic, targets hepatic glycolate oxidase to reduce urinary oxalate (UOx) levels, addressing the metabolic root cause of PH1. This study aimed to evaluate whether treatment with lumasiran is associated with improved kidney survival compared with historical controls.

Researchers analyzed data from lumasiran-treated PH1 patients enrolled in the ILLUMINATE-A trial and compared them with a control cohort from the Rare Kidney Stone Consortium registry. Control participants met similar inclusion criteria—age ≥ 6 years, chronic kidney disease (CKD) stages 1–3b, and UOx ≥ 0.7 mmol/1.73 m²/24 h—and were managed using standard supportive measures. Propensity score–based inverse probability of treatment weighting (IPTW) was applied to balance groups by age, sex, baseline UOx, estimated glomerular filtration rate (eGFR), and age at PH1 diagnosis. Kidney survival was assessed using Kaplan-Meier estimates and Cox proportional hazards models with bootstrap confidence intervals.

During a median follow-up of 11.9 years in the 116 historical controls, 46 ESKD events occurred. In contrast, among 39 patients treated with lumasiran (median follow-up 4.6 years), no ESKD events were reported. Weighted analyses demonstrated excellent covariate balance. The 4-year ESKD-free survival estimate was 88% (95% CI 82%–94%) in the control cohort versus 100% (95% CI 91%–100%) in the lumasiran-treated group. Treatment with lumasiran was associated with a markedly reduced hazard of ESKD (HR 0.049; 95% CI 0.031–0.094; P < .001).

“These results suggest a clinically meaningful reduction in ESKD risk in PH1 patients with lumasiran treatment,” the study authors concluded.

Reference:
Sas DJ, Vaughan LE, Schulte P, Tencer T, Milliner DS, Lieske JC. Kidney survival in patients with primary hyperoxaluria type 1 treated with lumasiran compared with historical controls. Presented at: American Society of Nephrology Kidney Week; November 5–9, 2025; Houston, Texas.