Renoprotective effects of dapagliflozin versus pentoxifylline in stage 2–3 non-diabetic chronic kidney disease patients

Abstract Background Chronic kidney disease (CKD) is a major contributor to global morbidity and mortality, with limited therapeutic options in non-diabetic populations [1, 2]. Sodium–glucose cotransporter-2 (SGLT2) inhibitors and pentoxifylline exert renoprotective effects via distinct hemodynamic and anti-inflammatory mechanisms [3-4]; however, direct comparative data in non-diabetic CKD remain scarce. Objective To compare the renoprotective efficacy of dapagliflozin versus pentoxifylline in patients with stage 2–3 non-diabetic CKD, with clearly predefined primary and secondary outcomes. Methods This randomized controlled trial included 210 patients allocated into three groups: dapagliflozin (Group A), pentoxifylline (Group B), and standard therapy (Group C). The primary outcome was the change in estimated glomerular filtration rate (eGFR) over 12 months. Secondary outcomes included serum creatinine, blood urea nitrogen (BUN), protein-to-creatinine ratio, urinary albumin-to-creatinine ratio, renal ultrasonographic grading (standardized assessment), and urinary sediment analysis. CKD etiology was documented and incorporated into adjusted analyses. A revised multivariate regression model was applied with reporting of effect sizes (odds ratios and confidence intervals). Results Dapagliflozin demonstrated the most pronounced improvement in renal function, with eGFR increasing from 42.16 to 46.54 mL/min/1.73 m² (p < 0.001). Significant reductions were observed in serum creatinine (1.71 to 1.26 mg/dL, p < 0.001) and BUN (30.51 to 23.51 mg/dL, p < 0.001). Proteinuria and albuminuria were significantly reduced in Group A compared with Groups B and C. Pentoxifylline showed moderate but statistically significant improvements in proteinuria and inflammatory-related markers. In contrast, standard therapy was associated with deterioration in renal parameters. Adjusted regression analysis identified dapagliflozin (OR = 2.216, p < 0.001) and pentoxifylline (OR = 1.951, p = 0.002) as independent predictors of renal improvement. Conclusion Both dapagliflozin and pentoxifylline improve renal outcomes in non-diabetic CKD; however, dapagliflozin provides superior and more consistent benefits across functional and biochemical domains. These findings support its broader use in non-diabetic CKD populations [5].