Effect of SGLT2 Inhibitors on Kidney Outcomes in IgAN Following Kidney Transplant: A Real-World Comparative Analysis

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown renal-protective effects in proteinuric kidney diseases, including native IgA nephropathy (IgAN). However, their efficacy in preventing recurrence or progression of IgAN following kidney transplantation remains unclear. This study aimed to evaluate the association between post-transplant SGLT2 inhibitor use and renal outcomes in kidney transplant recipients with a history of IgAN. Methods: We performed a retrospective cohort analysis using the TriNetX Global Collaborative Network. Adults (≥18 years) with a diagnosis of IgAN (ICD-10: N02.8, N05, N05.8) and kidney transplant status (Z94.0) were included. Patients were stratified into two cohorts: Cohort A: Patients who received an SGLT2 inhibitor (empagliflozin, dapagliflozin, or canagliflozin; n=2,068) Cohort B: Patients with no record of SGLT2 use (n=28,005) Primary outcomes included graft failure, dialysis dependence, IgAN recurrence (hematuria), proteinuria, and mortality, assessed using risk ratios and Kaplan–Meier survival analyses. Results: Dialysis dependence was significantly lower in SGLT2 users (1.9%) vs. non-users (7.8%) (RR: 0.25; 95% CI: 0.18–0.34; p<0.001). Graft failure was also reduced in SGLT2 users (0.5% vs. 1.6%) (RR: 0.30; 95% CI: 0.16–0.56; p<0.001). Recurrence of IgAN (hematuria) occurred in 0.5% of SGLT2 users vs. 0.3% in non-users (RR: 1.47; p=0.24), a difference that did not reach statistical significance. Proteinuria rates were slightly lower in the SGLT2 group (0.5% vs. 0.6%; RR: 0.84; p=0.59). Mortality appeared higher in SGLT2 users (0.5% vs. 0.05%; RR: 9.67), but event counts were small and Kaplan–Meier analysis showed no significant survival difference (p=0.97). Conclusion: In kidney transplant recipients with IgA nephropathy, SGLT2 inhibitor use was associated with a significant reduction in graft failure and dialysis dependence, without an increased risk of hematuria recurrence or proteinuria. These findings support the potential role of SGLT2 inhibitors in improving post-transplant renal outcomes in patients with IgAN, warranting further prospective studies to validate safety and long-term efficacy.