Long-term real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors

ABSTRACT Background Sparsentan has emerged as a promising therapeutic option for immunoglobulin A nephropathy. However, data on its effectiveness in real-world settings, particularly in combination with sodium–glucose cotransporter 2 (SGLT2) inhibitors remain limited. In our previously published real-world cohort (n = 23), we demonstrated a significant reduction in proteinuria with concurrent SGLT2 inhibitor treatment. Here, we present 1-year follow-up data. Methods After 1 year, 17 patients (74%) from the initial cohort remained on sparsentan therapy. As described previously, patients had been on stable, maximally tolerated renin–angiotensin system (RAS) inhibition and stable SGLT2 inhibitor therapy before replacement of RAS inhibition with sparsentan; eligibility required an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m2 and a urine protein/creatinine ratio (UPCR) >0.75 g/g. Results Baseline median (interquartile range) eGFR (Chronic Kidney Disease Epidemiology Collaboration) was 48 ml/min/1.73 m2 (34–66) and median UPCR was 1.55 g/g (0.90–1.85). At 1-year follow-up, UPCR remained significantly reduced (P = .0001) to a median of 0.54 g/g (0.34–0.76), corresponding to a relative reduction of 61% (45–95). The median chronic eGFR slope was −1.5 ml/min/1.73 m2 per year (−7.51 to +3.75) at follow-up. Conclusions In this 1-year follow-up of our real-world cohort, sparsentan was associated with a significant and sustained reduction in proteinuria over 12 months, with a numerically less steep eGFR decline during follow-up, even in patients already receiving SGLT2 inhibitors.