Potential Role of SGLT-2 Inhibitors in Improving Allograft Function and Reducing Rejection in Kidney Transplantation

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have demonstrated renoprotective and cardioprotective benefits beyond their antiglycemic effects. Their potential utility in kidney transplant recipients (KTRs) for preserving graft function and reducing rejection risk is currently under active investigation. Preliminary studies indicate that SGLT-2i therapy stabilizes estimated glomerular filtration rate (eGFR), decreases glomerular hyperfiltration, and improves metabolic outcomes in KTRs. Emerging clinical evidence also suggests that SGLT-2i may be associated with reduced rates of acute rejection, although direct immunosuppressive actions remain unclear. Experimental findings further suggest that SGLT-2i modulates gene regulation pathways involved in inflammation, oxidative stress, and fibrosis, contributing to improved allograft outcomes. Current safety data in KTRs are reassuring, without significant increases in urinary tract infections or adverse graft events. Nevertheless, long-term prospective studies specific to transplant populations are lacking. This review summarizes available evidence regarding the mechanisms of action, clinical efficacy, and safety profile of SGLT-2i in kidney transplantation, emphasizing their metabolic, hemodynamic, inflammatory, and immunomodulatory effects.