Abstract
Epidemiological evidence on the relationship between lead exposure and mortality in specific chronic kidney disease (CKD) populations is limited. We aimed to examine the relationship between urinary lead and blood lead concentrations and all-cause mortality in US patients with CKD. This cohort study included 2320 participants with CKD from the National Health and Nutrition Examination Survey (2005-2018), with follow-up until December 31, 2019. All-cause mortality was ascertained by matching US National Death Index records. Hazard ratios (HRs) and 95% confidence intervals (CI) for urinary lead and blood lead concentrations in relation to all-cause mortality were estimated using a weighted Cox regression model. During a median follow-up period of 79 months, a total of 625 participants with CKD succumbed to mortality. Compared to the lowest quartile, the highest quartile of urine and blood lead concentrations was associated with an increased risk of all-cause mortality, with HRs and corresponding 95% CIs of 1.77 (1.05-2.99) and 2.65 (1.38-5.10), respectively. Furthermore, each additional unit increase in urinary and blood lead concentrations was associated with HRs for all-cause mortality of 1.21 (95% CI 1.06-1.38) and 1.09 (95% CI 1.01-1.19), respectively. Kaplan-Meier survival curve analysis and restricted cubic regression spline curve analysis demonstrated significant positive associations between elevated blood lead levels, elevated urinary lead levels, and all-cause mortality risk (P < 0.05). A nonlinear concentration-response relationship was observed between blood lead level and all-cause mortality risk (P(Nonlinear) < 0.05), with an inflection point at a concentration of 1.613 µg/dL. Subgroup analysis as well as sensitivity analysis yielded consistent findings. Our findings demonstrate that elevated levels of lead in urine and blood are associated with a significantly increased mortality risk among patients with CKD, underscoring the importance of reducing lead exposure to mitigate mortality risk in individuals at high risk for CKD.