A study presented at ERA 2025 validates the use of proteinuria as a surrogate endpoint for FSGS clinical trials.
New results from the PARASOL consortium highlight the successful validation of proteinuria reduction as a surrogate endpoint for kidney failure in focal segmental glomerulosclerosis (FSGS), reinforcing its utility for future clinical trials. The validation, which leveraged the UK National Registry of Rare Kidney Diseases (RaDaR) registry, marks a critical step in establishing reliable, feasible endpoints for drug development in this rare and progressive condition.
The PARASOL initiative combined data from 9 registries across North America and Europe to identify markers that predict long-term outcomes in patients with biopsy-proven or genetic FSGS. Among 1626 eligible participants in the PARASOL cohort, reduction in UPCR to below 0.7 g/g by 24 months was associated with an 85% lower hazard of kidney failure (HR, 0.15; 95% CI, 0.09–0.26), along with a survival advantage of +0.27.
Presented at the 62nd European Renal Association (ERA 2025) Congress, these findings were independently validated in 465 patients from RaDaR, a longstanding national registry with phenotyping of patients with rare kidney diseases. Despite demographic and clinical differences, including older age, lower baseline eGFR, and higher baseline proteinuria, RaDaR participants showed similar predictive value for proteinuria response. At the 0.7 g/g threshold, responders had a hazard ratio for kidney failure of 0.07 (95% CI, 0.02 to 0.27) and a +0.29 survival difference, closely mirroring the PARASOL results.
According to Daniel Gale, MBChB, PhD, director of the UK-based RaDaR Registry and the St Peter's Chair of Nephrology at University College London, validation in RaDaR represents a key milestone, demonstrating that findings from PARASOL are not confined to research settings or selective cohorts and confirming proteinuria response is a robust, reproducible surrogate endpoint that holds across diverse FSGS populations, including those captured in real-world clinical registries.
In an interview at ERA 2025, Gale noted this level of cross-cohort consistency supports the adoption of UPCR-based endpoints in clinical trials, offering a practical alternative to highly variable eGFR-based outcomes that would require much larger sample sizes to detect meaningful effects.
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