Klotho: A possible mechanism of action of SGLT2 inhibitors preventing episodes of acute kidney injury and cardiorenal complications of diabetes

Diabetes and cardiorenal comorbidities are major global health concerns, with high economic burdens and mortality rates. Sodium glucose co-transporter-2 inhibitors (SGLT2is) are novel US Food and Drug Administration (FDA)-approved antihyperglycemics with unexpected protective potential against cardiorenal diseases in patients with or without type 2 diabetes mellitus (T2DM). Despite initial concerns, the incidence of episodes of acute kidney injury (AKI) was significantly lower in patients taking SGLT2i compared with other therapies or placebo. Evolving data suggest a link between SGLT2is and the anti-aging protein Klotho in the amelioration of diabetes and cardiorenal diseases. Here, we consider Klotho and SGLT2is as a novel therapeutic approach for the management of AKI and other cardiorenal complications in patients with or without diabetes.