title: Development and characterization of a pseudo multiple reaction monitoring method for the quantification of human uromodulin in urine.
abstract: BACKGROUND
  Uromodulin is the most abundant protein in healthy human urine. Recently it has been suggested as a specific biomarker of renal tubular damage. We have developed a novel pseudo multiple reaction monitoring (pseudo MRM) for the protein's quantification in human urine.
  
  
  RESULTS
  Selection of two peptides allowed quantification of uromodulin in human urine. The pseudo MRM quantified uromodulin in healthy individuals between 21 and 1344 nM and in autosomal dominant tubulointerstitial kidney disease-UMOD patients between 2 and 25 nM.
  
  
  CONCLUSIONS
  The pseudo MRM allows greater confidence in assay specificity than traditional MRM methods and quantified uromodulin at concentrations higher than achievable by ELISA. Differences in urinary uromodulin concentration related to the rs4293393 promoter variant in the UMOD gene was confirmed. This method will be used to further investigate uromodulin as a biomarker of renal injury.
authors.affiliation: Division of Molecular & Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland.|Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hammond
authors.affiliation: Proteomics Core Facility, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland.
authors.forename: Suzette
authors.initials: S
authors.lastname: Moes
authors.affiliation: Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis.|Institute of Physiology, Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Youhanna
authors.affiliation: Division of Physiology, Department of Physiology & Medical Physics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Jennings
authors.affiliation: Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis.|Institute of Physiology, Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Division of Molecular & Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland.|Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis.
authors.forename: Alex
authors.initials: A
authors.lastname: Odermatt
authors.affiliation: Proteomics Core Facility, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056, Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Jenö
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D059748:Proteolysis; D053719:Tandem Mass Spectrometry / Q000379:methods; D016482:Urinalysis / Q000379:methods*; D058949:Uromodulin / Q000032:analysis / Q000652:urine*
chemical_list: D015415:Biomarkers; D058949:Uromodulin
keywords: MS; Tamm-Horsfall protein; autosomal-dominant tubulointerstitial kidney disease-UMOD; biomarker; multiple reaction monitoring; protein quantification; pseudo multiple reaction monitoring; selected reaction monitoring; thick ascending limb