Triglyceride-Glucose Index and Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio as Novel Predictors of AKI: A Large-Scale Prospective Study

Background: Our study aimed to comprehensively investigate the associations of the Triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio with the risk of AKI ,based on the data from the UK Biobank. Methods: A total of 427,659 individuals remained for the final analysis. According to the TyG index levels, patient data were divided into 5 quartiles. The primary outcome of this study was incident AKI, defined based on the International Classification of Diseases edition 10. Participant follow-up started at inclusion in the UK Biobank and was censored on December 31, 2022 or on the date of the first AKI. The analysis involved the utilization of Cox proportional hazard models, log-rank tests, and Kaplan-Meier cumulative incidence graphs. Mediation analyses were carried out to examine the impact of hypertension, diabetes, and dyslipidemia on the relationships between the risk of AKI, the the TyG index, and TG/HDL-C ratio. Results: Of 427,659 included participants, 22,447 (5.25%) participants developed incident AKI. The median TyG index and TG/HDL-C ratio were 8.68 (IQR 8.31–9.08) and 2.43 (IQR 1.51–3.96), respectively. The risk of AKI elevated progressively with the increased quartiles of both the TyG index and TG/HDL-C ratio, as indicated by Kaplan-Meier curves. Elevated quartiles of the TyG index or TG/HDL-C ratio exhibited strong associations with AKI risk in comparison to lower quartiles, demonstrating respective hazard ratios (95% CI) of 1.16 (1.11-1.22) and 1.05 (1.00-1.10) (p<0.001). After full covariate adjustment,the adjusted smoothed plots displayed U-shaped associations between TyG index and incident AKI,and the relation between TG/HDL-C ratio and the hazard of incident AKI followed a reverse J-shape (p for nonlinearity < 0.001). The results did not change by the sensitivity analysis. In mediation analyses, variables like hypertension, type-2 diabetes, and dyslipidemia emerged as notable intermediaries in the connections between the incident AKI, the TyG index, and the TG/HDL-C ratio (intermediation proportions: 83.5%,74.5% ). Conclusion: Association was detected between the increased TyG index or ratio of TG to HDL-C and increased AKI risks. These associations were mainly influenced by a higher incidence of hypertension, type-2 diabetes, and dyslipidemia. Funding: Government Support – Non-U.S.