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Uranium associations with kidney outcomes vary by urine concentration adjustment method

Journal of Exposure Science & Environmental Epidemiology volume 24, pages 58–64 (2014)Cite this article

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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.

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Abbreviations

BMI:

body mass index

Cd:

cadmium

Cr:

creatinine

CV:

coefficient of variation

DU:

depleted uranium

eGFR:

estimated glomerular filtration rate

GFR:

glomerular filtration rate

ICP-MS:

inductively coupled plasma–mass spectrometer

IQC:

internal quality control

ln- :

natural logarithm

MDL:

method detection limit

MDRD:

Modification of Diet in Renal Disease

NAG:

N-acetyl-β-D-glucosaminidase

NHANES:

National Health and Nutrition Examination Survey

NIST:

National Institute of Standards and Technology

NU:

natural uranium

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Acknowledgements

This research was supported by National Institute of Environmental Health Sciences grant 2 ES007198 (Dr Weaver), Korea Research Foundation-2000-00545 (Dr Lee) from the Korea Research Foundation, and the Education and Research Center for Occupational Safety and Health at the Johns Hopkins Bloomberg School of Public Health ((T42 OH0008428) National Institute for Occupational Safety and Health). The funding sources had no involvement in study design; data collection, analysis or interpretation; manuscript writing; or decisions to submit the work for publication.

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Authors and Affiliations

  1. Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA

    Rebecca Shelley, Jacqueline Agnew, Brian S Schwartz & Virginia M Weaver

  2. Institute of Industrial Medicine, SoonChunHyang University, Asan, South Korea

    Nam-Soo Kim & Byung-Kook Lee

  3. New York State Department of Health, Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, Albany, New York, USA

    Patrick J Parsons & Amy J Steuerwald

  4. Department of Environmental Health Sciences, School of Public Health, University at Albany, Albany, New York, USA

    Patrick J Parsons & Amy J Steuerwald

  5. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA

    Bernard G Jaar, Genevieve Matanoski & Brian S Schwartz

  6. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Bernard G Jaar, Brian S Schwartz & Virginia M Weaver

  7. Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

    Bernard G Jaar, Jeffrey Fadrowski & Virginia M Weaver

  8. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

    Jeffrey Fadrowski

  9. Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA

    Andrew C Todd

  10. Biostatistical Consulting, Cincinnati, Ohio, USA

    David Simon

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Correspondence to Virginia M Weaver.

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Shelley, R., Kim, NS., Parsons, P. et al. Uranium associations with kidney outcomes vary by urine concentration adjustment method. J Expo Sci Environ Epidemiol 24, 58–64 (2014). https://doi.org/10.1038/jes.2013.18

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