Research Square · Oct 20, 2026
Association between insulin resistance surrogate indices and incident chronic kidney disease among the population with cardiovascular-kidney-metabolic syndrome stage 0-3: a cohort study
By Wu J, Lin M, Tan X et al.
Background Insulin resistance (IR) is central to the cardiovascular-kidney-metabolic (CKM) syndrome. Routine-biochemistry surrogate indices of IR are widely used, but prospective evidence that they identify high-renal-risk individuals within the CKM staging framework is lacking. We compared six such indices for association with new-onset chronic kidney disease (CKD) in middle-aged and older adults at CKM stage 0–3. Methods From the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study we included 4,068 adults aged ≥ 45 years at CKM stage 0–3 with blood data in both waves, excluding baseline eGFR < 60 mL/min/1.73 m², CKM stage 4, and missing or implausible key values. Incident CKD was defined as an eGFR ≥ 60 mL/min/1.73 m² in 2011 and an eGFR < 60 mL/min/1.73 m² in 2015 (2021 CKD-EPI creatinine equation). Six indices (TyG, cumulative TyG, TyG-WC, TyG-WHtR, TyG-BMI, METS-IR) entered logistic regression per 1-SD increase and in tertiles, with stepwise adjustment (M1 demographic and behavioural factors; M2 plus blood pressure, LDL-C, uric acid and BUN; M3 plus baseline creatinine, hypertension and diabetes). Restricted cubic splines, ROC analysis (DeLong), eight-subgroup interaction tests and three sensitivity analyses were performed. Results Over four years, 120 participants developed CKD (2.9%). All six indices were higher at baseline in incident cases (P = 0.048 to < 0.001); incidence was highest in the top tertile for all, with significant trends for five (TyG-WHtR 2.14% to 4.20%, P = 0.001). Per-SD odds ratios (ORs) were 1.19–1.42 in crude and M1 models. TyG and cumulative TyG lost significance in M2, whereas the four composite indices remained significant after full adjustment: TyG-WC 1.27 (95% CI 1.03–1.56), TyG-WHtR 1.28 (1.03–1.59), TyG-BMI 1.28 (1.04–1.58) and METS-IR 1.26 (1.03–1.54). No non-linearity was detected (P = 0.087–0.948) and AUCs were 0.563–0.592. Cumulative TyG and METS-IR associations were stronger at BMI < 24 kg/m² (interaction P = 0.035, 0.043); composite-index associations were confined to non-drinkers (interaction P = 0.016–0.041). Excluding BMI ≥ 28 kg/m² or removing uric acid did not change composite-index significance. Conclusions In CKM stage 0–3, composite indices (especially TyG-BMI and TyG-WHtR) were more robustly associated with incident CKD than TyG alone, while all indices showed limited discrimination. These low-cost indices may complement CKM staging in identifying subgroups needing eGFR monitoring.