CENTRAL ASIAN JOURNAL OF NEPHROLOGY

Keyword: Meta-Analysis

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Congress Abstract
Morphological Basis of the Nephroprotective Effect of SGLT2 Inhibitors in Chronic Kidney Disease: A Systematic Review and Meta-Analysis
Central Asian Journal of Nephrology, 2(2, Suppl. 1), 2026, cajn_A39, https://doi.org/10.63946/cajn/19520
ABSTRACT: Background: Chronic kidney disease (CKD) is characterized by progressive loss of kidney function associated with intraglomerular hypertension, hyperfiltration, podocyte injury, tubular damage, and tubulointerstitial fibrosis. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated nephroprotective effects beyond glycemic control. This study aimed to quantitatively assess the effect of SGLT2 inhibitors on CKD progression and to summarize the morphological mechanisms underlying their nephroprotective effects.
Methods: A systematic review and quantitative meta-analysis of randomized controlled trials (RCTs) evaluating SGLT2 inhibitors and renal outcomes was performed. The primary quantitative analysis included the CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical heterogeneity was assessed using the I² statistic and Cochran’s Q test. Published evidence on morphological and structural renal changes associated with SGLT2 inhibition was additionally analyzed.
Results: SGLT2 inhibitors reduced the risk of the primary renal composite endpoint in CREDENCE (HR 0.70; 95% CI 0.59–0.82), DAPA-CKD (HR 0.61; 95% CI 0.51–0.72), and EMPA-KIDNEY (HR 0.72; 95% CI 0.64–0.82). The pooled analysis demonstrated a significant reduction in the risk of CKD progression (HR 0.68; 95% CI 0.62–0.75), corresponding to an approximately 32% relative risk reduction. Heterogeneity between studies was low (I²=17.5%). Morphological evidence demonstrated attenuation of glomerular hyperfiltration, preservation of podocytes and the glomerular filtration barrier, reduction of tubular injury, and attenuation of tubulointerstitial fibrosis.
Conclusion: SGLT2 inhibitors are associated with a significant reduction in the risk of CKD progression. Their nephroprotective effects appear to involve complementary hemodynamic, glomerular, tubular, and tubulointerstitial mechanisms. The consistency between clinical trial findings and morphological evidence supports a multifactorial basis for SGLT2 inhibitor-mediated nephroprotection.