Chronic cardiorenal syndrome: cardio-renal protective effect of SGLT2i

Chronic cardiorenal syndrome (types 2 and 4) arises from chronic dysfunction of either the heart or kidneys, leading to progressive deterioration of the other organ. The coexistence of cardiac and renal dysfunction significantly complicates treatment strategies and is associated with high morbidity and mortality, with currently limited effective therapeutic options. Given the demonstrated cardiorenal protective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i), it is important to explore their potential mechanisms and clinical application value in the treatment of non-diabetic chronic cardiorenal syndrome.

This review systematically analyzes the multiple mechanisms of SGLT2i and integrates the latest clinical trial evidence to evaluate their potential application in the management of non-diabetic chronic cardiorenal syndrome. It specifically examines their cardiorenal protective pathways beyond glucose-lowering effects, including diuretic and natriuretic actions, improved hemodynamics, inhibition of neurohormonal overactivation, modulation of inflammation and oxidative stress, and enhancement of vascular endothelial function.

Recent clinical studies confirm that SGLT2i exert cardiorenal protection through multiple mechanisms and demonstrate potential for improving prognosis in non-diabetic patients with cardiorenal syndrome. Combination therapy with mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists shows synergistic therapeutic advantages.

SGLT2i provide a novel therapeutic strategy for chronic cardiorenal syndrome, with their multi-target mechanisms offering new perspectives for combined cardiorenal protection. However, further clinical research is required to optimize treatment protocols and address practical challenges in their application.