Abstract: TH-PO1090
Kidney Survival in Patients with Primary Hyperoxaluria Type 1 Treated with Lumasiran Compared with Historical Controls
Session Information
- CKD: Therapies, Innovations, and Insights
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Sas, David J., Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
- Vaughan, Lisa E., Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, United States
- Schulte, Phillip, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, United States
- Tencer, Tom, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
- Milliner, Dawn S., Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
- Lieske, John C., Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
Background
Primary hyperoxaluria type 1 (PH1) is associated with risk of end-stage kidney disease (ESKD) from excess hepatic oxalate production and urinary excretion. The novel small inhibitory RNA lumasiran reduces urinary oxalate (UOx) excretion in PH1 patients (pts). To estimate the potential magnitude of ESKD reduction, we compared lumasiran-treated PH1 pts to historical controls not receiving lumasiran.
Methods
Lumasiran-treated PH1 pts were from the ILLUMINATE-A trial. The control cohort comprised PH1 pts from the Rare Kidney Stone Consortium registry who satisfied similar inclusion criteria (age ≥6 years [y], CKD stages 1 to 3b, UOx ≥0.7 mmol/1.73m2/24h). Controls were managed with high fluid intake and crystal inhibitors, and most (85%) received pyridoxine. Lumasiran’s effect on kidney survival was estimated by inverse probability of treatment weighting (IPTW) using propensity scores and included the variables age, sex, UOx, eGFR, and age at PH1 diagnosis. Kaplan-Meier ESKD-free survival estimates are reported with 95% confidence intervals (CIs). IPTW Cox proportional hazards regression evaluated the association between treatment group and time to incident ESKD, with bootstrap 95% CIs and P value.
Results
During median follow-up of 11.9 y (95% CI: 9.5-13.8), 46 ESKD events occurred in 116 control pts. No ESKD events occurred during median follow-up of 4.6 y (95% CI: 4.2-4.6) in 39 lumasiran-treated pts. In the weighted sample, pt characteristics were well balanced. Estimated ESKD-free survival at 4 y was 88% (95% CI: 82%-94%) in the control cohort and 100% (95% CI: 91%-100%) in the lumasiran cohort (Figure 1). Lumasiran treatment was associated with reduced ESKD hazard compared with controls (HR [95% CI]: 0.049 [0.031-0.094], P<0.001).
Conclusion
These results suggest a clinically meaningful reduction in ESKD risk in PH1 pts with lumasiran treatment.
Funding
- Commercial Support – Alnylam Pharmaceuticals