title: Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C.
abstract: Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) μg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs=0.5; p<0.001). After adjustment, ln (urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln (urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient=4.1 mL/min/1.73 m2; 95% confidence interval=1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.
authors.affiliation: Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615N. Wolfe St., Rm. 7041, Baltimore, MD 21205, USA. vweaver@jhsph.edu
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Weaver
authors.forename: Nam-Soo
authors.initials: NS
authors.lastname: Kim
authors.forename: Byung-Kook
authors.initials: BK
authors.lastname: Lee
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Parsons
authors.forename: June
authors.initials: J
authors.lastname: Spector
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fadrowski
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Jaar
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Steuerwald
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Todd
authors.forename: David
authors.initials: D
authors.lastname: Simon
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D002104:Cadmium / Q000633:toxicity / Q000652:urine*; D003404:Creatinine / Q000097:blood*; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D055316:Cystatin C; D002104:Cadmium; D003404:Creatinine