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UMOD-ulating CKD risk: untangling the relationship between urinary uromodulin, blood pressure, and kidney disease

Michael Turner1, Natalie Staplin2

  • 1Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Kidney International
|November 22, 2021
PubMed

Insights

Higher urinary uromodulin is genetically linked to reduced kidney function and increased blood pressure. Decreased kidney function partially explains the link to higher blood pressure, but not vice versa.

Area of Science:

  • Nephrology
  • Cardiovascular Science
  • Genetic Epidemiology

Background:

  • Uromodulin (UMOD) is a key urinary protein with established roles in kidney physiology.
  • Observational studies suggest links between UMOD levels, kidney function, and blood pressure, but causality remains unclear.

Purpose of the Study:

  • To investigate the causal relationship between genetically predicted urinary uromodulin levels and kidney function.
  • To explore the causal relationship between genetically predicted urinary uromodulin levels and blood pressure.
  • To determine the mediating role of kidney function in the association between uromodulin and blood pressure.

Main Methods:

  • Utilized Mendelian randomization (MR) analysis, a genetic epidemiology technique, to infer causality.
  • Employed bidirectional and multivariable MR models to assess the interplay between uromodulin, kidney function, and blood pressure.
  • Examined the validity of MR assumptions and the implications of the findings.

Main Results:

  • Genetically predicted higher urinary uromodulin levels were associated with lower estimated glomerular filtration rate (eGFR), indicating reduced kidney function.
  • Genetically predicted higher urinary uromodulin levels were associated with higher systolic blood pressure.
  • Multivariable MR indicated that reduced kidney function partially mediated the association between uromodulin and higher blood pressure.

Conclusions:

  • Urinary uromodulin influences kidney function and blood pressure through distinct but interconnected pathways.
  • Findings support a causal role for uromodulin in kidney disease pathogenesis and hypertension.
  • Further research is warranted to explore therapeutic strategies targeting uromodulin.

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