Abstract
BACKGROUND: Population aging is a pivotal trend observed globally, and the exposure to heavy metals can exacerbate the aging process and lead to kidney damage. However, the impact of combined heavy metal exposure on renal function among older individuals remains elusive. Our study employs machine learning techniques to delve into the effects and underlying mechanisms of mixed exposure to heavy metals on the renal function of the aging population. METHODS: This study extracted comprehensive data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2020. A total of 3,175 participants aged 60 years and above, with complete information on six metals - lead, cadmium, manganese, cobalt, mercury, and selenium, along with relevant covariates, were included in the study. To assess the impact of single or mixed metal exposure on the renal function of older adult individuals, various statistical techniques were employed: multiple logistic regression, weighted quantitative sum (WQS) regression, Bayesian kernel machine regression (BKMR), and mediation effects analysis. RESULTS: Multiple logistic regression revealed that selenium and manganese were protective factors for chronic kidney disease (CKD). Cobalt was a risk factor for CKD. High concentrations of lead, cadmium, and cobalt were risk factors for urinary albumin creatinine ratio (ACR). WQS analyses revealed that mixed metal exposure was positively correlated with estimated glomerular filtration rate (eGFR) but negatively correlated with CKD. Selenium and manganese can neutralize the effects of other metals on eGFR. Mixed metal exposure was positively correlated with ACR, with lead and cadmium having a substantial effect. Mediation analysis showed that uric acid (UA) had a mediating effect of 9.7% and -19.7% in the association between mixed metals exposure and proteinuria and CKD, respectively. CONCLUSION: The impact of heavy metals on renal function in the older adult differs from that of adolescents and adults. This study suggests that elevated levels of mixed metals exposure are linked to proteinuria and CKD, with UA serving as a mediating factor.