Triglyceride-glucose index and triglyceride-to-high-density lipoprotein cholesterol ratio as novel predictors of acute kidney injury: an analysis of the UK biobank

The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized markers of insulin resistance, but their associations with acute kidney injury (AKI) risk remain understudied in large populations. Using data from the UK Biobank (UKB) and the UK Biobank Pharma Proteomics Project (UKB-PPP), this study investigated whether these indices are linked to AKI risk. A total of 427,659 participants from the UKB were retrospectively analyzed and stratified into quintiles based on TyG index or TG/HDL-C ratio. Among them, 22,447 (5.25%) developed AKI. Kaplan-Meier analysis revealed a progressive increase in AKI risk across rising quintiles of both indices (p < 0.001). In fully adjusted models, the highest quintiles of the TyG index and TG/HDL-C ratio were significantly associated with increased AKI risk compared to the lowest quintiles, with hazard ratios of 1.16 (95% CI: 1.11–1.22) and 1.05 (95% CI: 1.00–1.10), respectively. Mediation analysis within the UKB-PPP cohort identified 11 proteins that significantly mediated the relationship between these metabolic indices and AKI. These findings suggest that both the TyG index and TG/HDL-C ratio are potential predictors of AKI, and that protein mediators may partly underlie these associations.