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

Anna Köttgen1, Shih-Jen Hwang, Martin G Larson

  • 173 Mount Wayte Avenue, Suite #2, Framingham, MA 01702, USA.

Journal of the American Society of Nephrology : JASN
|December 5, 2009
PubMed

Insights

Elevated uromodulin levels in urine predict the future onset of chronic kidney disease (CKD). These higher concentrations are also linked to specific UMOD gene variants, suggesting a genetic component to kidney disease risk.

Area of Science:

  • Nephrology
  • Genetics
  • Biomarkers

Background:

  • Common variants near the UMOD gene correlate with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR).
  • The relationship between uromodulin levels, UMOD gene variants, and CKD risk remains unclear.

Purpose of the Study:

  • To investigate the association between urinary uromodulin concentrations and the risk of developing CKD.
  • To examine the relationship between UMOD gene variants and urinary uromodulin levels.

Main Methods:

  • An age- and gender-matched case-control study of 200 participants from the Framingham Heart Study (FHS) with incident CKD.
  • Analysis of baseline urinary uromodulin concentrations and genotyping at the rs4293393 polymorphism.
  • Replication of genotype association in the Atherosclerosis Risk in Communities (ARIC) Study.

Main Results:

  • Urinary uromodulin concentrations were 51% higher in CKD cases compared to controls.
  • A 1-SD increase in uromodulin concentration was associated with a 1.72-fold increased odds of developing CKD.
  • Lower urinary uromodulin concentrations were observed with each copy of the C allele at rs4293393 in both study cohorts.

Conclusions:

  • Elevated urinary uromodulin concentrations precede the clinical onset of CKD.
  • Urinary uromodulin levels are associated with a common UMOD gene polymorphism, indicating a potential genetic influence on CKD risk.

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