Sodium glucose cotransporter 2 inhibition and renal ischemia: implications for future clinical trials

Sodium glucose cotransporter 2 inhibitors are increasingly being recognized for renal protective effects that are largely independent of hemoglobin A1c-lowering or glucosuria-related endpoints. Accordingly, there is growing interest in potential renal benefits with sodium glucose cotransporter 2 inhibitors in nondiabetic patients to take advantage of natriuresis-mediated effects on blood pressure, proteinuria, and renal function. In this issue of Kidney International, Zhang et al. report renoprotective effects with the sodium glucose cotransporter 2 inhibitor lusogliflozin in an ischemia-reperfusion injury model under nondiabetic conditions, thereby providing important mechanistic insights into the use of these agents in chronic kidney disease.