Abstract
BackgroundA 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.MethodsIn 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.ResultsAmong 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).ConclusionsThis 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.
Highlights
A common variant of the UMOD gene was linked with prevalent chronic kidney disease (CKD) in large, genomics consortia
A common variant in the region of the UMOD gene was recently discovered in association with chronic kidney disease (CKD) in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium of 19,877 participants of European ancestry
In the Heart and Soul Study, a well-characterized cohort of persons with established coronary artery disease (CAD), we evaluated whether baseline urine uromodulin concentrations would distinguish participants with and without subsequent progression to CKD after 5 years of follow-up
Summary
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. A common variant in the region of the UMOD gene was recently discovered in association with chronic kidney disease (CKD) in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium of 19,877 participants of European ancestry. Patients with cardiovascular disease are a population at high risk for developing CKD [6,7] Atherosclerosis in both large arteries and in the microvasculature appears to contribute to declining kidney function [8,9]. In the Heart and Soul Study, a well-characterized cohort of persons with established coronary artery disease (CAD), we evaluated whether baseline urine uromodulin concentrations would distinguish participants with and without subsequent progression to CKD after 5 years of follow-up. In the Heart and Soul Study, a well-characterized cohort of persons with established coronary artery disease (CAD), we evaluated whether baseline urine uromodulin concentrations would distinguish participants with and without subsequent progression to CKD after 5 years of follow-up. [10] In addition, we evaluated whether UMOD genotype was associated with urine concentrations of uromodulin in these participants
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