TyG-BMI and risk of CKD progression: Mediation by oxidative stress, fibrosis, and metabolic dysfunction

Abstract

To investigate the association between the triglyceride-glucose-body mass index (TyG-BMI) and chronic kidney disease (CKD) progression in individuals across the cardiovascular-kidney-metabolic spectrum, and to evaluate the potential mediation by biomarkers of oxidative stress, inflammation, and fibrosis. This study included 9265 adults stratified into cardiovascular-kidney-metabolic stages 0 to 4. Logistic regression and restricted cubic splines assessed the relationship between TyG-BMI and CKD progression. Mediation analysis quantified the indirect effects of the uric acid-to-high-density lipoprotein ratio, fibrosis-4 index, and red cell distribution width-to-albumin ratio. The primary finding of this study is that elevated TyG-BMI significantly increases the risk of chronic kidney disease (CKD) progression. Specifically, for each unit increase in TyG-BMI, the risk of CKD progression rose by 16% (OR = 1.16; 95% CI:1.01-1.30). This association was quantitatively and significantly mediated by the uric acid-to-high-density lipoprotein ratio, the fibrosis-4 index, and the red cell distribution width-to-albumin ratio, indicating the involvement of oxidative, fibrotic, and inflammatory pathways. Our analysis suggests that elevated TyG-BMI may be associated with an increased risk of CKD progression, potentially mediated through oxidative, inflammatory, and fibrotic pathways. These findings warrant further investigation to confirm the potential clinical relevance of TyG-BMI and the implicated pathways.

Keywords: cardiovascular-kidney-metabolic; fibrosis-4 index (FIB-4); mediation analysis; metabolic dysfunction; triglyceride-glucose body mass index (TYG-BMI); uric acid-to-HDL ratio (UHR).

Figure 1.

Flow chart of the participants’ selection. CKD = chronic kidney disease, CKM = cardiovascular-kidney-metabolic, GED = general educational development, NHANES = National Health and Nutrition Examination Survey

Figure 2.

Dose-response relationships between cardiometabolic indices and chronic kidney. The solid line represents the estimated utility values, and the 2 dashed lines represent the 95% confidence interval of the estimated utility values. The nodes are set to 4, corresponding to the 5th, 35th, 65th, and 95th percentiles. The model was adjusted for age, sex, race/ethnicity, systolic blood pressure, smoking status, and history of cardiovascular disease, marital status, education level, family poverty-income ratio (PIR), alcohol use, drugs for hypertension, diabetes, and depression status. BMI = body mass index, CI = confidence interval, FIB-4 = fibrosis-4 index, LDL = low-density lipoprotein, OR = odds ratio, PIR = family poverty-income ratio, RAR = red cell distribution width-to-albumin ratio, UHR = uric acid-to-high-density lipoprotein ratio.

Figure 3.

Analysis of the mediating effect. The model was adjusted for age, sex, race/ethnicity, systolic blood pressure, smoking status, and history of cardiovascular disease, marital status, education level, family poverty-income ratio (PIR), alcohol use, drugs for hypertension, diabetes, and depression status. BMI = body mass index, FIB-4 = fibrosis-4 index, LDL = low-density lipoprotein, PIR = family poverty-income ratio, RAR = red cell distribution width-to-albumin ratio, UHR = uric acid-to-high-density lipoprotein ratio.