Diverging trajectories of cardiorenal protection: From early benefit to late attenuation with multifactorial target achievement across cardiovascular kidney-metabolic syndrome stages

BACKGROUND The extent to which achieving multiple metabolic treatment targets confers sustained cardiorenal protection across all stages of cardiovascular - kidney - metabolic (CKM) syndrome remains uncertain. METHODS This multicenter retrospective study used data from the China Renal Data System (CRDS) to investigate the association between achieving multiple metabolic targets (blood pressure, fasting blood glucose, LDL-C control) and cardiorenal outcomes across stages of CKM syndrome. RESULTS The proportion of patients meeting all three metabolic targets decreased markedly with advancing CKM stage. Kaplan-Meier curves showed increasing risks of cardiovascular-renal events and mortality across higher stages (P < 0.001). After adjustment, higher metabolic scores were linked to lower risks: for cardiovascular-renal outcomes, HR 0.82 (95% CI 0.77-0.87) for score 1, 0.72 (0.68-0.77) for score 2, and 0.65 (0.57-0.73) for score 3. Stratified analysis showed significant risk reduction in early CKM stages but not in advanced stages. Restricted cubic spline models indicated nonlinear associations between LDL-C and both outcomes, and between FBG, systolic BP, and mortality, after full adjustment (all P < 0.05). CONCLUSIONS The findings underscore the need for stage-specific management strategies in CKM syndrome.