Divergent Renal Benefits of Sodium-Glucose Cotransporter-2 Inhibitors and Mineralocorticoid Receptor Antagonists in Nondiabetic Kidney Disease
Abstract
Introduction: Nondiabetic kidney disease (NDKD) is a major contributor to chronic kidney disease worldwide. Although renin-angiotensin system inhibitors (RASi) remain standard therapy, sodium-glucose cotransporter-2 inhibitors (SGLT2i), non-steroidal mineralocorticoid receptor antagonists (non-steroidal MRAs), and glucagon-like peptide-1 receptor agonists are now recommended in clinical guidelines. However, direct comparative evidence to guide their prioritization in NDKD is limited.
Methods: We performed a systematic review and Bayesian network meta-analysis of randomized controlled trials enrolling adults with NDKD. The primary endpoint was the annualized change in estimated glomerular filtration rate (eGFR) slope; secondary endpoints included urine protein-to-creatinine ratio (UPCR), blood pressure, and biochemical safety parameters.
Results: Eighteen trials were included. SGLT2i, as add-on to RASi, produced the greatest preservation of kidney function compared with RASi alone (mean difference [MD] 12.1 mL/min/1.73 m2/year; 95% credible interval [CrI] 3.9 to 20.4). Non-steroidal MRA achieved the largest reduction in proteinuria versus RASi (UPCR MD -0.4 g/g; 95% CrI: -1.0 to -0.2). SGLT2i also yielded the greatest systolic blood pressure reduction versus RASi (MD -9.1 mm Hg vs. RASi; 95% CrI: -11.7 to -6.5). Surface-under-the-cumulative-ranking probabilities identified SGLT2i as most effective for eGFR slope preservation (99.8%) and non-steroidal MRA as most effective for…
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