Cardiorenal Syndrome in Type 2 Diabetes Mellitus - Rational Use of Sodium-glucose Cotransporter-2 Inhibitors.

Abstract

Cardiorenal syndrome (CRS) in people with type 2 diabetes mellitus (T2DM) illustrates the bidirectional link between the heart and the kidneys, with acute or chronic dysfunction of one organ adversely impacting the function of the other. Of the five subtypes identified, type 1 and 2 CRS occur because of the adverse impact of cardiac conditions on the kidneys. Type 3 and 4 occur when renal conditions affect the heart, and in type 5, systemic conditions impact the heart and kidneys concurrently. The cardiovascular and renoprotective benefits evidenced with sodium-glucose cotransporter-2 (SGLT2) inhibitors make them a potential choice in the management of CRS. Cardiovascular protection is mediated by a reduction in cardiac workload, blood pressure, and body weight; with improvement in lipid profile, uric acid levels, and adaptive ketogenesis process. Renoprotection is facilitated by reduction in albuminuria and hypoxic stress, and restoration of tubuloglomerular feedback. The favourable effect on cardiovascular complications and death, as well as renal complications and progression to end-stage kidney disease, has been confirmed in clinical trials. Guidelines endorse first-line use of SGLT2 inhibitors after metformin in patients with T2DM with high cardiovascular risk, chronic kidney disease or both. Since most trials with SGLT2 inhibitors excluded subjects with acute illness, patients with CRS subtypes 1 and 3 have not been studied adequately, making SGLT2 initiation in clinical practice challenging. Ongoing trials may provide evidence for SGLT2 inhibitor use in CRS. This review aims to enhance understanding of CRS and provide guidance for judicious use of SGLT2 inhibitors in T2DM.