Uromodulin levels associate with a common UMOD variant and risk for incident CKD

Anna Köttgen, Shih Jen Hwang, Martin G. Larson, Jennifer E. Van Eyk, Qin Fu, Emelia J. Benjamin, Abbas Dehghan, Nicole L. Glazer, W. H.Linda Kao, Tamara B. Harris, Vilmundur Gudnason, Michael G. Shlipak, Qiong Yang, Josef Coresh, Daniel Levy, Caroline S. Fox

Research output: Contribution to journalArticlepeer-review

Abstract

Common variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein), associate with chronic kidney disease (CKD) and estimated GFR (eGFR). Whether uromodulin levels associate with UMOD variants or with the risk for developing CKD is unknown. We conducted an age-and gendermatched case-control study (n=200) of incident CKD (eGFR<60 ml/min per 1.73m2) within the Framingham Heart Study (FHS). Baseline urinary uromodulin concentrations were related to case-control status 9.9 yr later and to genotype at rs4293393. As a replication set, we tested the genotype association with uromodulin concentration in the Atherosclerosis Risk in Communities (ARIC) Study (n = 42). Geometric means of uromodulin concentrations were 51% higher in case than in control subjects (P = 0.016). The adjusted odds ratio of CKD per 1-SD higher concentration of uromodulin was 1.72 (95% confidence interval 1.07 to 2.77; P= 0.03) after accounting for CKD risk factors and baseline eGFR. We observed lower urinary uromodulin concentrations per each copy of the C allele at rs4293393 in both cohorts. In summary, elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region.

Original languageEnglish (US)
Pages (from-to)337-344
Number of pages8
JournalJournal of the American Society of Nephrology
Volume21
Issue number2
DOIs
StatePublished - Feb 2010

ASJC Scopus subject areas

  • Nephrology

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