Associations between proteins and heavy metals in urine at low environmental exposures: Evidence of reverse causality

• Published in: Toxicology letters Vol. 210; no. 3; pp. 345 - 352
• Main Authors: Chaumont, Agnès, Nickmilder, Marc, Dumont, Xavier, Lundh, Thomas, Skerfving, Staffan, Bernard, Alfred
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 05.05.2012; Elsevier
• Subjects: Adolescent; adolescents; albumins; Albuminuria; Albuminuria - chemically induced; at-risk population; Basic Medicine; beta-microglobulin; binding sites; Biological and medical sciences; blood; Cadmium; Cadmium - urine; Chemical and industrial products toxicology. Toxic occupational diseases; creatinine; Cross-Sectional Studies; developed countries; Environmental Exposure; Farmakologi och toxikologi; Female; Heavy metals; Humans; Kidney - drug effects; Lead; Lead - urine; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Metals and various inorganic compounds; Metals, Heavy - toxicity; Metals, Heavy - urine; Multivariate Analysis; Nephrology. Urinary tract diseases; Pharmacology and Toxicology; protein; Proteinuria; Proteinuria - chemically induced; Regression Analysis; Retinol-binding; Retinol-binding protein; Reverse causality; risk; specific gravity; Toxicology; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; urine; β2-microglobulin; Albuminuria; U-Creat; SD; Tβ4; Lead; pI; U-Cd; BMI; Cadmium; B-Pb; U-β2m; MT; U-RBP; IQR; U-SG; ACBP; Heavy metals; B-Cd; HMW; LMW; Reverse causality; U-Alb; β2-microglobulin; Proteinuria; Retinol-binding protein; microglobulin; Biological fluid; Toxicity; Vitamin; Binding protein; Human; Urine; Urinary system disease; Transition metal; Exposure; Heavy metal; Retinol; β; Adolescent; Environment; Reversibility; Causality; β2-Microglobulin
• ISSN: 0378-4274; 1879-3169; 1879-3169
• DOI: 10.1016/j.toxlet.2012.02.005

► We assessed the renal effects of environmental exposure to metals in adolescents. ► Low-molecular-weight proteins correlated significantly with cadmium or lead in urine. ► The physiological variation in the protein renal uptake might explain these findings. Heavy metals can cause renal effects on vulnerable populations but it is uncertain whether these metals still pose health risks at the low exposure levels now prevailing in most industrialized countries. In a cross-sectional study performed on 736 adolescents, we assessed the associations between the concentrations of cadmium and lead in blood and urine and the urinary concentrations of albumin and of low-molecular-weight (LMW) proteins, retinol-binding protein (RBP) and β2-microglobulin. Multiple regression analyses were tested using urinary markers normalized to urinary creatinine or specific gravity. Median metal concentrations were in blood (μg/L): lead, 15.1, cadmium, 0.18 and in urine (μg/g creatinine): cadmium, 0.09 and lead, 0.82. Multivariate analyses revealed significant associations in urine between RBP and cadmium as well as between β2-microglobulin and lead whereas no associations were seen with metals in blood. These associations were completely abolished in subjects with increased urinary albumin, which may be explained by the competitive inhibition of LMW protein reabsorption by albumin. Given the evidence that cadmium and lead circulate mainly bound to LMW proteins, these associations observed at low exposure might simply reflect the interindividual variations in the renal uptake of proteins sharing the same affinity for tubular binding sites.