CARDIOVASCULAR-KIDNEY-METABOLIC SYNDROME STAGES AND RISKS OF INCIDENT CHRONIC KIDNEY DISEASE: A NATIONWIDE COHORT STUDY IN CHINA

The growing recognition of the pathophysiological connections between obesity and metabolic risk factors such as diabetes, chronic kidney disease (CKD), and cardiovascular diseases (CVD) has led to the widespread acceptance of the conception of cardiovascular-kidney-metabolic (CKM) syndrome, which is defined as a systemic disorder characterized by pathophysiological interactions among metabolic risk factors, CKD, and the cardiovascular system, leading to multiorgan dysfunction and a high rate of adverse cardiovascular outcomes and has gradually become a public health concern. Previous studies has revealed that the coexistence of metabolic abnormalities and CKD is significantly associated with adverse cardiovascular outcomes. However, the interaction between CVD and metabolic risk factors in relation to renal function progression remains unclear. Meanwhile, most current evidence derives from Western populations, while studies focusing on Asian cohorts—especially Chinese populations—are notably scarce. Given the distinct genetic backgrounds, lifestyle patterns, and disease profiles in China, the generalizability of previous findings to this population remains questionable. This study therefore aims to investigate the association between CKM syndrome staging and incident CKD in a representative sample of middle-aged and older Chinese adults. Elucidating these relationships in an understudied population may inform the development of targeted prevention and improved risk stratification strategies.

This was a prospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS), including participants aged ≥45 years with complete baseline (2011) and follow-up (2015) data. Incident CKD was defined as a new-onset estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Participants were stratified by CKM stages based on established criteria. Multivariable logistic regression adjusted for demographics, comorbidities, and lifestyle factors was used to evaluate the independent associations between CKM stages and incident CKD risk.

The study included 5,978 participants, with a mean age of 58.6 years (SD ± 9.0) and 44.0% male. During the 4-year follow-up period, incident CKD developed in 269 participants, yielding an overall incidence rate of 4.50% (95% CI 3.98-5.07). After full adjustment, CKM stage 2 (OR 2.11, 95% CI 1.20 to 3.69, P = 0.009) and stage 4 (OR 2.08, 95% CI 1.12 to 3.89, P = 0.021) were independently associated with increased risks of incident CKD, while CKM stage 1 patients and non-CKM patients showed no significant difference in CKD incidence (OR 1.19, 95% CI 0.66 to 2.14, P = 0.557).

Table 1. Baseline Characteristics by CKM Stage​

Table 2. Incident of chronic kidney disease by different CKM stages

Table 3. Association between CKM stages and risk of incident CKD across different adjustment models

This nationwide prospective cohort study provides compelling evidence that advanced stages of cardiovascular-kidney-metabolic (CKM) syndrome are significantly associated with an increased risk of incident chronic kidney disease among middle-aged and older adults in China. Our findings demonstrate that CKM stage 2 and beyond hold substantial clinical predictive value for the development of CKD.