Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Abstract

Background and objectives The urinary excretion of uromodulin is influenced by common variants in the UMOD gene, and it may be related to NaCl retention and hypertension. Levels of uromodulin are also dependent of the renal function, but other determinants remain unknown.Design, setting, participants, & measurements We tested associations between the urinary excretion of uromodulin; medical history and medication; serum and urinary levels of electrolytes, glucose, and uric acid; and the genotype at the UMOD/Protein Disulfide Isomerase-Like, Testis Expressed locus (rs4293393 and rs12446492); 943 participants from the CARTaGENE Cohort, a random sample from the Canadian population of 20,004 individuals, were analyzed. Participants with available genotyping were obtained from a substudy addressing associations between common variants and cardiovascular disease in paired participants with high and low Framingham risk scores and vascular rigidity indexes.Results The population studied was 5469 years old, with 51% women and eGFR of 9614 ml/min per 1.73 m 2 . Uromodulin excretion was 25 (11-42) mg/g creatinine. Using linear regression, it was independently higher among patients with higher eGFR, the TT genotype of rs4293393, and the TT genotype of rs12446492. The fractional excretions of urate and sodium showed a strong positive correlation with uromodulin, likely linked to the extracellular volume status. The presence of glycosuria and the use of uricosuric drugs, which both increased the fraction excretion of urate, were independently associated with a lower uromodulin excretion, suggesting novel interactions between uric acid and uromodulin excretion. ConclusionsIn this large cohort, the excretion of uromodulin correlates with clinical, genetic, and urinary factors. The strongest associations were between uric acid, sodium, and uromodulin excretions and are likely linked to the extracellular volume status.

Tamm Horsfall Glycoprotein and Uromodulin

“…There were several other interesting findings from the Canadian study (2). Consistent with prior studies, uromodulin excretion was significantly higher in individuals with the rs4293393T variant.…”

“…Two new publications (1,2) in this issue of the Clinical Journal of the American Society of Nephrology (CJASN) further add to this knowledge. In this editorial, we will review recent developments in this area and provide a context for the two new investigations.…”

“…These studies help us understand the relationship between uromodulin excretion and excretion of urinary solutes, eGFR, and clinical conditions (1,2). The correlation between eGFR, kidney mass, and uromodulin excretion rate suggests that urinary uromodulin might be a biomarker for renal tubular mass and function.…”

“…Each study was a large cross-sectional survey in which urinary samples were obtained, and the urinary uromodulin concentration was determined. The Canadian study by Troyanov et al (2) included 943 participants randomly selected from 20,000 individuals in the CARTaGENE Study, Quebec's populationbased biobank for public health and personalized genomics. A strength of this investigation was the ability to perform genetic analysis of the uromodulin SNP rs4293393.…”

Urinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study

“…Finally, a number of studies have shown that uromodulin levels are affected by UMOD polymorphisms. 31,32 While the focus of this study was not on uromodulin genotype, further studies need to evaluate if uromodulin genotype is associated with clinical UTI in humans.…”