Implications of Complete Proteinuria Remission at any Time in Focal Segmental Glomerulosclerosis: Sparsentan DUET Trial.
In the DUET trial of sparsentan for focal segmental glomerulosclerosis, achieving complete remission of proteinuria at any time during follow-up, even if not sustained, was associated with a significantly slower rate of eGFR decline.
Background
Focal segmental glomerulosclerosis is a rare glomerular disease with high unmet clinical need, and there is growing interest in proteinuria as a surrogate endpoint for regulatory approval of new therapies. Sparsentan is a dual endothelin and angiotensin receptor antagonist studied in the DUET trial; this analysis assessed whether achieving complete remission of proteinuria relates to long-term kidney outcomes.
Study design
The analysis included all 108 patients who received at least one dose of sparsentan in the DUET trial and its open-label extension, followed for a median of 47.0 months. Evaluations every 12 weeks captured blood pressure, edema, proteinuria, and kidney function. Complete remission was defined as a first-morning urine protein-to-creatinine ratio of 0.3 g/g or less.
Key findings
During follow-up, 46 patients (43%) experienced at least one complete remission, with 61% of these occurring within 12 months of starting sparsentan. A higher sparsentan dose and baseline subnephrotic-range proteinuria were associated with greater likelihood of complete remission. Achieving at least one complete remission was associated with a significantly slower rate of eGFR decline compared with patients who did not achieve remission. The antiproteinuric effect of sparsentan was additive to that of concomitant immunosuppressive treatment, and no unanticipated adverse events occurred.
Clinical implications
The authors conclude that sparsentan can be administered safely over extended periods with a sustained antiproteinuric effect, and that achieving complete remission at any time, even if not maintained, may indicate a favorable treatment response and predict improved kidney function outcomes. This supports the value of proteinuria remission as a meaningful treatment target in focal segmental glomerulosclerosis.
Category
Research
Source
Kidney Int Rep
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