SGLT2 Inhibitors in Glomerulonephritis: Beyond Nephroprotection?

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for glycaemic control in type 2 diabetes, have demonstrated substantial renal and cardiovascular protective effects across various chronic kidney diseases (CKD), including glomerulonephritis. Beyond their established haemodynamic and metabolic benefits, recent evidence points to additional mechanisms of action potentially relevant to immune-mediated kidney diseases, such as the modulation of inflammation, immunometabolism, and oxidative stress. Randomised clinical trials (DAPA-CKD and EMPA-KIDNEY) and real-world observational studies consistently show that SGLT2 inhibitors reduce proteinuria and slow estimated glomerular filtration rate (eGFR) decline in patients with glomerulonephritis, including IgA nephropathy and focal segmental glomerulosclerosis. These benefits may extend to patients with stable immunosuppression. Further data are needed in this subgroup. Importantly, SGLT2 inhibitors display a favourable safety profile, even among those with immunosuppressed status. Again, further evidence is awaited in this respect. Despite these promising findings, unanswered questions remain regarding their efficacy in nephrotic syndrome, early-stage disease, and in comparison or combination with other supportive therapies. Overall, the evolving evidence supports the inclusion of SGLT2 inhibitors as a key component of supportive therapy in glomerulonephritis, with potential benefits extending beyond proteinuria reduction.