The role of SGLT2 inhibitors in renal protection beyond diabetes
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This systematic review examines the role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in renal protection beyond diabetes, particularly in non-diabetic chronic kidney disease (CKD). Searches were conducted in PubMed, SciELO, Google Scholar and Cochrane, including randomized clinical trials, meta-analyses, preclinical studies and mechanistic reviews. Available evidence shows that SGLT2i, such as empagliflozin and dapagliflozin, slow eGFR decline, reduce albuminuria and decrease adverse renal outcomes, with significant risk reductions demonstrated in large-scale trials. In the EMPA-KIDNEY trial, empagliflozin reduced cardiorenal events by 28% (HR = 0.72; 95% CI: 0.64–0.82), with consistent effects in non-diabetic patients. Meta-analyses confirm sustained renal benefits and an acceptable safety profile, despite an increased risk of urogenital infections in non-diabetic individuals. At the molecular level, proposed mechanisms include restoration of tubuloglomerular feedback, AMPK activation, suppression of inflammatory and profibrotic pathways (NF-κB, TGF-β) and metabolic reprogramming via ketone body–mediated inhibition of mTORC1. These findings support SGLT2i as a promising therapeutic strategy for CKD irrespective of diabetic status.
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