Serum Trace Elements and Concurrent Renal, Hepatic, and Electrolyte Biomarkers: A Secondary Cross-Sectional Analysis of SPES

The relationships between circulating trace elements and routinely measured renal, hepatic, and electrolyte biomarkers remain incompletely characterized. We conducted a secondary cross-sectional analysis of 19 serum elements and concurrent biochemistry in 4137 adults from the Exposure Study on Susceptible People (SPES), Campania, Italy. Creatinine, alanine aminotransferase (ALT), gamma-glutamyl transferase, and potassium were primary outcomes; additional renal, hepatic, mineral, and protein-related measurements were secondary or exploratory. Associations were estimated with covariate adjustment, multiple imputation, and within-family false-discovery-rate control. Per doubling of concentration, lithium was associated with 0.54% higher creatinine (95% confidence interval, 0.22-0.86%). Antimony associations with ALT and potassium were sensitive to the handling of below-quantification concentrations and were not established among directly quantified measurements. Secondary and exploratory findings included higher bilirubin with iron and lower bilirubin with copper; higher ferritin with iron and lower ferritin with cobalt; higher uric acid with strontium, selenium, lithium, and arsenic; and higher albumin, total protein, and total calcium with selenium. Additional albumin adjustment approximately halved the selenium coefficients for total calcium and total protein. The primary associations were small, and their biological and clinical relevance remains uncertain. These cross-sectional findings identify hypotheses concerning renal handling, iron status, and overlapping protein-associated biochemistry.