Sodium-Glucose Cotransporter-2 Inhibitors in Non-Diabetic Chronic Kidney Disease: A Meta-Analysis of Renal Outcomes

Abstract

Introduction: Chronic kidney disease (CKD) progresses irrespective of diabetes. SGLT2 inhibitors have shown cardiorenal benefits in diabetic populations, but their role in non-diabetic CKD remains debated. This review synthesizes evidence on renal protection in biopsy-proven glomerulonephritis and hypertensive nephrosclerosis.
Methods: Systematic literature search of PubMed, Embase, and Cochrane (2015–2024) for randomized controlled trials (RCTs) comparing SGLT2 inhibitors to placebo in adults with eGFR 25–75 mL/min/1.73m² without diabetes. Primary outcome: decline in eGFR ≥40% or progression to end-stage renal disease (ESRD). Fixed-effects meta-analysis used.
Results: Six RCTs (n=12,844) met criteria. Pooled analysis showed a 28% relative risk reduction (RRR) for primary outcome (HR 0.72; 95% CI 0.64–0.81, p<0.001). Urinary albumin-to-creatinine ratio (UACR) declined by 19% (mean difference -19.2%, 95% CI -25.1 to -13.3). Adverse events (mainly genitourinary infections) were mild, no excess acute kidney injury.
Discussion: Benefit was consistent across baseline eGFR strata and proteinuria levels, suggesting class effect independent of glycemic status. Mechanisms likely involve intraglomerular pressure reduction and anti-fibrotic pathways. Limitations include short follow-up (median 2.5 years) and lack of hard renal survival data.
Conclusions: SGLT2 inhibitors significantly slow CKD progression in non-diabetic patients, supporting guideline expansion beyond diabetes.