Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Non-Diabetic Chronic Kidney Disease

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular morbidity and mortality in patients with type 2 diabetes. Furthermore, recent clinical studies have revealed that SGLT2 inhibitors decrease the risk of renal function impairment in patients with type 2 diabetes. However, the effects of SGLT2 inhibitors on non-diabetic chronic kidney disease (CKD) remains unclear. Regarding long-term clinical outcomes, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial explicitly showed improvements in cardiovascular outcomes in patients presenting with heart failure, even in the absence of diabetes. The reduction in heart failure in patients without diabetes was confirmed following empagliflozin administration in the EMPagliflozin outcomE tRial in patients with chrOnic heart failure with Reduced ejection fraction (EMPEROR-Reduced) trial. A recent systematic review and meta-analysis of DAPA-HF and EMPEROR-Reduced showed improvements in the composite renal endpoint regardless of the presence of diabetes or baseline estimated glomerular filtration rate. The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) trial evaluated patients with CKD with or without type 2 diabetes, irrespective of whether SGLT2 inhibitor dapagliflozin was added for renin-angiotensin system blockade as background renoprotective therapy. In this trial, dapagliflozin reduced the hazard ratio for a composite renal and cardiovascular death endpoint in patients with CKD attributed to various causes, with or without type 2 diabetes.

Keywords: Chronic kidney disease (CKD); Hypoxia-inducible factor (HIF); Inflammation; Oxidative stress; Sodium-glucose cotransporter 2 (SGLT2) inhibitors; Tubuloglomerular feedback (TGF).