Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis

Abstract

ABSTRACT Background The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. Methods This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. Results Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin–angiotensin system blockers were included. Proteinuria from baseline changed by –35%, –41%, –45% and –48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by –6%, –3%, –8% and –10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30–0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: –3.7 versus –5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. Conclusions The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.