The AST/ALT ratio as a mediator of heavy metal exposure and diabetic kidney disease (DKD) risk: A NHANES study

Abstract The potential impact of heavy metal exposure on the progression of diabetic kidney disease (DKD) remains a subject of scientific inquiry. While some studies have hinted at a correlation, definitive evidence is still lacking. It is important to note that certain links, such as the association between cadmium exposure and chronic kidney disease, have been established in prior research. This study seeks to examine the potential link between heavy metal exposure and the risk of DKD. This cross-sectional study included adult type 2 diabetes mellitus (T2DM) patients from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. The study analyzed nine types of urinary heavy metals and three types of blood heavy metals. Survey-weighted logistic regression, restricted cubic spline (RCS) analysis, weighted quantile sum regression (WQS) regression, and Bayesian kernel machine regression (BKMR) model were employed to evaluate the effects of single and mixed heavy metal exposure on DKD. Subgroup analyses were conducted based on age and gender. Mediation analysis was used to assess the mediating effect of the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. Additionally, a series of sensitivity analyses were performed. The final analysis included 5,124 individuals (2011–2018), of whom 896 (17.49%) were classified as having DKD. Weighted logistic regression indicated that urinary barium (UBa), urinary cobalt (UCo), urinary cesium (UCs), urinary thallium (UTl), blood cadmium (BCd), and blood lead (BPb) were associated with DKD. RCS analysis indicated a nonlinear relationship between UBa, UCo, UCs, UTl, BPb, and DKD. Both WQS regression and BKMR model consistently demonstrated a negative correlation between urinary mixed heavy metal exposure and the risk of DKD, while blood mixed heavy metal exposure was positively correlated with the risk of DKD, identifying UBa as the primary protective contributor and BCd as the primary risk contributor. Subgroup analysis revealed that age and gender could modify the association between heavy metal exposure and the risk of DKD. Finally, mediation analysis revealed that the AST/ALT ratio played a crucial potential mediating role in the association between heavy metal exposure and the prevalence of DKD. Our findings offer a comprehensive perspective on the relationship between heavy metals (particularly protective UBa and risk-associated BCd) and DKD risk, which holds significant implications for environmental control and early prevention of DKD, it is important to note that our cross-sectional design precludes causal inferences. Future longitudinal studies are needed to establish causality and inform intervention strategies.