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Open Access Research article

Uromodulin concentrations are not associated with incident CKD among persons with coronary artery disease

Michael G Shlipak12*, Yongmei Li1, Caroline Fox3, Josef Coresh4, Carl Grunfeld25 and Mary Whooley12

Author Affiliations

1 Division of General Internal Medicine, San Francisco VA Medical Center; San Francisco, CA, USA

2 Department of Medicine University of California, San Francisco; San Francisco, CA, USA

3 National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA; Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (CSF), USA

4 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

5 Division of Metabolism and Endocrine Sections, San Francisco VA Medical Center; San Francisco, CA, USA

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BMC Nephrology 2011, 12:2  doi:10.1186/1471-2369-12-2

Published: 14 January 2011

Abstract

Background

A common variant of the UMOD gene was linked with prevalent chronic kidney disease (CKD) in large, genomics consortia. One community-based study found that urine concentrations of the uromodulin protein forecast risk of incident CKD. This study within persons with known coronary artery disease (CAD) evaluated whether uromodulin concentrations could distinguish CKD risk.

Methods

In the Heart and Soul Study, the UMOD snp (12917707) was genotyped in 879 individuals with baseline creatinine clearance (CrCl) measured from a 24-hour urine collection. Uromodulin protein was measured from stored urine specimens among a subset of 120 participants, balanced by genotype. Incident CKD cases (N = 102) were defined by an initial CrCl > 70 ml/min and a 5-year follow-up CrCl <60 ml/min; controls (N = 94) were matched on age, sex, and race.

Results

Among 527 self-described White participants with DNA, 373 (71%) were homozygous for the dominant allele (G/G), 133 (25%) were heterozygous (G/T) and only 21 (4%) were homozygous for the minor allele (T/T). The T/T genotype had an approximately 11 ml/min higher CrCl than the other 2 groups, but this difference did not reach statistical significance (p = 0.20). The T/T genotype had significantly lower uromodulin levels than the common G/G genotype, and the G/T genotype had intermediate levels. However, uromodulin concentrations were similar between cases and controls (44 vs. 48 mg/dL, p = 0.88).

Conclusions

This study among a cohort of persons with established CAD found no association between urine uromodulin and incident CKD, although UMOD genotype was associated with urine uromodulin concentrations.