title: Uranium associations with kidney outcomes vary by urine concentration adjustment method.
abstract: Uranium is a ubiquitous metal that is nephrotoxic at high doses. Few epidemiologic studies have examined the kidney filtration impact of chronic environmental exposure. In 684 lead workers environmentally exposed to uranium, multiple linear regression was used to examine associations of uranium measured in a 4-h urine collection with measured creatinine clearance, serum creatinine- and cystatin-C-based estimated glomerular filtration rates, and N-acetyl-β-D-glucosaminidase (NAG). Three methods were utilized, in separate models, to adjust uranium levels for urine concentration--μg uranium/g creatinine; μg uranium/l and urine creatinine as separate covariates; and μg uranium/4 h. Median urine uranium levels were 0.07 μg/g creatinine and 0.02 μg/4 h and were highly correlated (rs=0.95). After adjustment, higher ln-urine uranium was associated with lower measured creatinine clearance and higher NAG in models that used urine creatinine to adjust for urine concentration but not in models that used total uranium excreted (μg/4 h). These results suggest that, in some instances, associations between urine toxicants and kidney outcomes may be statistical, due to the use of urine creatinine in both exposure and outcome metrics, rather than nephrotoxic. These findings support consideration of non-creatinine-based methods of adjustment for urine concentration in nephrotoxicant research.
authors.affiliation: Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shelley
authors.affiliation: Institute of Industrial Medicine, SoonChunHyang University, Asan, South Korea.
authors.forename: Nam-Soo
authors.initials: NS
authors.lastname: Kim
authors.affiliation: 1] Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New York State Department of Health, Albany, New York, USA [2] Department of Environmental Health Sciences, School of Public Health, University at Albany, Albany, New York, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Parsons
authors.affiliation: Institute of Industrial Medicine, SoonChunHyang University, Asan, South Korea.
authors.forename: Byung-Kook
authors.initials: BK
authors.lastname: Lee
authors.affiliation: Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Agnew
authors.affiliation: 1] Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [3] Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Jaar
authors.affiliation: 1] Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New York State Department of Health, Albany, New York, USA [2] Department of Environmental Health Sciences, School of Public Health, University at Albany, Albany, New York, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Steuerwald
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Matanoski
authors.affiliation: 1] Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA [2] Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fadrowski
authors.affiliation: 1] Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA [2] Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA [3] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schwartz
authors.affiliation: Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Todd
authors.affiliation: Biostatistical Consulting, Cincinnati, Ohio, USA.
authors.forename: David
authors.initials: D
authors.lastname: Simon
authors.affiliation: 1] Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [3] Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Weaver
mesh_terms: D000328:Adult; D003404:Creatinine / Q000097:blood / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007854:Lead / Q000032:analysis / Q000097:blood; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D016273:Occupational Exposure; D013977:Tibia / Q000737:chemistry; D014501:Uranium / Q000652:urine*
chemical_list: D007854:Lead; D014501:Uranium; D003404:Creatinine