SGLT2 Inhibitors as Potential Agents for Prevention, Treatment, and/or Improved Recovery from Acute Kidney Injury

Acute kidney injury (AKI) results in rapid loss of blood filtration, reabsorption, and excretion of metabolic waste. AKI can progress to chronic kidney disease or even lead to premature death. AKI significantly worsens mortality in several of the top 20 leading causes of death as well as in populations of hospitalized patients postcoronary intervention or cardiac surgery or with sepsis. Experimental rodent models of AKI have been used to investigate the pathophysiology of the different AKI etiologies and their subtypes due to challenges of mechanistic studies and risks of acquiring kidney biopsies in human patients. The sodium-glucose cotransporter 2 (SGLT2), located on the apical membrane of early proximal tubules, is responsible for reabsorbing more than 90% of the filtered glucose back into the bloodstream. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced AKI severity and/or improved recovery when tested in rodent models of AKI. While SGLT2i are not currently approved by the FDA to treat AKI, there is clinical evidence to support their use as preventative agents. Of note, most clinical evidence for the use of SGLT2 inhibitors for AKI comes from studies in which AKI was not the primary end point. Data obtained from retrospective studies and animal models of AKI provide rationale for randomized clinical trials on SGLT2 inhibitors to prevent or improve recovery from AKI.