Efficacy and Safety of Dapagliflozin Combined with RAS Inhibitors in IgAN: A Real-World Study

Background: IgA nephropathy (IgAN) is a leading cause of chronic kidney disease (CKD) in China. Despite standard treatment with renin-angiotensin system (RAS) inhibitors, many patients still experience disease progression. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown renal protection in diabetic CKD, but their role in IgAN remains unclear. This study evaluated the effects of dapagliflozin combined with RAS inhibitors on proteinuria, renal function, and long-term outcomes in IgAN patients in a real-world setting. Methods: This single-center retrospective cohort study included 115 biopsy-confirmed IgAN patients with 24-hour urine protein >0.5 g/day, on RAS inhibitors for ≥12 weeks, and age >18 years. Patients were divided into RAS inhibitor alone (n=71) and RAS inhibitor plus dapagliflozin (n=44) groups. The primary endpoint was a composite renal outcome (≥40% decline in eGFR or end-stage renal disease). Secondary endpoints included proteinuria remission and safety. Results: Baseline characteristics were comparable between groups. At follow-up, the combination group had significantly lower 24-hour proteinuria [median (IQR): 0.41 (0.29, 0.66) vs. 0.61 (0.32, 1.43) g/day, P=0.025] and greater proteinuria reduction (60% vs 36%, P=0.002). eGFR was higher in the combination group (98.18±33.91 vs. 85.28±31.96 mL/min/1.73m2, P=0.042). Adverse event rates were similar (12.68% vs 11.63%, P=0.834). Over a median follow-up of 23.90±13.06 months, Kaplan-Meier analysis favored combination therapy (93.18% vs 88.73%, log-rank=5.268, P=0.022). Multivariate Cox analysis identified age and baseline eGFR as independent predictors of adverse renal outcomes. Conclusion: Dapagliflozin combined with RAS inhibitors significantly reduces proteinuria and slows renal function decline in IgAN patients, with a favorable safety profile. Age and baseline eGFR are independent risk factors for disease progression.