Initial effect of sodium-glucose cotransporter-2 inhibitors on kidney function in patients with immunoglobulin A nephropathy

Background: Optimized supportive therapy, including maximal renin-angiotensin-aldosterone system (RAAS) inhibition, is not always adequate in patients with IgA nephropathy (IgAN). This study evaluated the early effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on kidney function in patients with IgAN receiving RAAS inhibitors. Methods: Adult patients who were newly diagnosed with IgAN during 2020-2024, with baseline estimated glomerular filtration rate (eGFR) ≥35 mL/min/1.73 m2 , urine protein-to-creatinine ratio (UPCR) ≥0.8 g/g, and receiving RAAS inhibitors for ≥28 days were selected. The primary exposure was the incident use of SGLT2i. Changes in UPCR, urine albumin-to-creatinine ratio (UACR), and eGFR at 12 months were examined using mixed-effect models for repeated measures with inverse probability of treatment weighting. Results: SGLT2i use was associated with an early eGFR decline (mean difference, -5.39 mL/min/1.73 m2 ; 95% confidence interval [CI], -9.51 to -1.26) but was not significantly associated with the reduction in UPCR (geometric mean ratio [GMR], 0.90; 95% CI, 0.68-1.18) or UACR (GMR, 0.94; 95% CI, 0.67-1.34) at 12 months compared with non-users. However, subgroup and sensitivity analyses suggested a potential relationship between SGLT2i use and the reduction in proteinuria in patients with S0 lesions according to the Oxford Classification and baseline systolic blood pressure ≥130 mmHg, indicating possible benefits despite the absence of consistent statistical significance across analyses. Conclusion: In this real-world IgAN cohort, although SGLT2i use was not significantly associated with proteinuria reduction at 12 months, differential subgroup responses suggest that antiproteinuric benefits may be greater in patients without segmental glomerulosclerosis or with elevated systolic blood pressure.