Effect of statin therapy on renal and lipid outcomes in CKM syndrome stage 2: a meta-analysis of randomized controlled trials

Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined multisystem disorder integrating metabolic, renal, and cardiovascular dysfunction. CKM syndrome stage 2 represents an early, potentially reversible phase that offers a critical window for intervention. This meta-analysis evaluated the effects of statin therapy on renal and lipid outcomes in this population. 7 randomized controlled trials involving 490 participants were included. In the primary analysis, statin therapy showed a directionally favorable but non-significant trend toward improved estimated glomerular filtration rate (eGFR) and reduced 24-hour urinary total protein excretion (24h UTP), with no significant change in serum creatinine (Scr). Statins significantly reduced LDL-C (MD = - 52.18) and total cholesterol (MD = - 52.70), while changes in HDL-C and triglycerides were not significant. Subgroup analyses indicated numerically greater renal and lipid benefits with high-intensity regimens, longer treatment duration (≥ 26 weeks), and lower baseline eGFR, though no significant subgroup interactions were detected. Sensitivity analysis including a borderline CKM syndrome 2-3 trial characterized by higher renal risk, longer duration, and high-intensity atorvastatin rendered both renal and lipid outcomes statistically significant without altering effect direction. These findings suggest that statin therapy confers robust lipid-lowering efficacy and potential renoprotective effects in early CKM syndrome stages, particularly under conditions of greater baseline metabolic or renal burden. Statins may therefore serve as an early metabolic-renal intervention, warranting further validation in larger, stage-specific clinical trials.