Antiproteinuric effect of SGLT2 inhibitors in non-diabetic glomerulopathies is dependent on body mass index

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are emerging as an essential part of the standard of care for proteinuria in patients with chronic kidney disease. To date, no study has specifically evaluated the effects of body mass index (BMI) on the antiproteinuric efficacy of SGLT2. Here we report the impact of BMI on the antiproteinuric efficacy of SGLT2i in non-diabetic patients with glomerular diseases. Methods This is a retrospective, multicenter, international observational cohort study that included non-diabetic patients with biopsy-proven glomerular disease and proteinuria more than 0.5 g/24h who received SGLT-2i between 2016 and 2023. Laboratory values, including proteinuria and estimated glomerular filtration rate (eGFR), were obtained at baseline and after 3 to 6 months. Changes in laboratory values over time were analyzed using the paired signed-rank test. Results A total of 300 patients met the inclusion criteria. Median age was 51.82 [41, 62.65] years; 64.7% were male, 92.7% were white. The most common glomerular disease was IgA nephropathy (40.3%). Median eGFR was 52.26 [36.41, 74.01] ml/min/1.73 m². Median proteinuria was 1.60 [1.15, 2.91] g/24hr, and median serum albumin was 4.08 [3.80, 4.30] g/dl. Proteinuria reduction after SGLT2i initiation was significant only in overweight and obese patients (p<0.001 vs. 0.18). Patients with normal BMI did not experience the expected early drop in eGFR (p=0.16). Conclusion SGLT-2i are ineffective in proteinuria reduction in patients with BMI<25 kg/m², which contrasts with the significant proteinuria reduction in overweight and obese patients with glomerulopathies.