Effect of Renin Angiotensin-System Inhibitors on Reduction of Microalbuminuria in Normotensive Patients with Diabetes: A Systematic Review and Meta-Analysis

Background Evidence for treating moderately increased albuminuria [A2, urinary albumin-creatinine ratio (ACR) 30–299 mg/g] in normotensive patients with diabetes remains unclear. KDIGO supports the use of angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs), whereas ADA recommends against it in this population. We conducted a systematic review evaluating ACEi/ARB therapy in normotensive patients with diabetes with moderately increased albuminuria. Methods This systematic review was registered in PROSPERO (CRD42024571295). A comprehensive search was performed across PubMed, Embase, Cochrane, Scopus, and ClinicalTrials.gov. Randomized controlled trials involving normotensive patients with type 1 or type 2 diabetes and moderately increased albuminuria, comparing ACEi/ARB with placebo, were included. The primary outcome was a reduction in albuminuria; the secondary outcome was a change in estimated glomerular filtration rate (eGFR). Weighted mean differences (WMD) with 95% CI were calculated and pooled using a random-effects model. Results Thirteen RCTs involving 1374 participants met the inclusion criteria; nine trials used ACEi, and four used ARB. ACEi/ARB therapy significantly reduced albuminuria in both type 1 (-64.78% [95% CI -81.56, -47.99]; I2=73%, p <0.001) and type 2 diabetes (-60.09% [95% CI -80.93, -39.25]; I2=92%, p <0.0001). Four ACEi trials reported progression/regression outcomes. A 75% reduction in risk of progression to macroalbuminuria (A3) was observed (OR 0.25; 95% CI 0.13–0.49; I2=0%, p =0.99). Conclusion ACEi/ARB therapy in normotensive patients with diabetes with moderately increased albuminuria reduces albuminuria, suggesting potential renoprotection.