title: Prospects for urinary proteomics: exosomes as a source of urinary biomarkers.
abstract: Recent progress in biotechnology offers the promise of better medical care at lower costs. Among the techniques that show the greatest promise is mass spectrometry of proteins, which can identify proteins present in body fluids and tissue specimens at a large scale. Because urine can be collected in large amounts in a non-invasive fashion, the potential exists to use mass spectrometry to discover urinary biomarkers that are early predictors of renal disease, or useful in making therapeutic choices. Recently, the authors demonstrated that both membrane proteins and cytosolic proteins from renal epithelia are highly enriched in low-density urinary structures identified as exosomes. Exosomes were found to contain many disease-associated proteins including aquaporin-2, polycystin-1, podocin, non-muscle myosin II, angiotensin-converting enzyme, Na+ K+ 2Cl- cotransporter (NKCC2), thiazide-sensitive Na-Cl cotransporter (NCC), and epithelial sodium channel (ENaC). Potentially, other disease biomarkers could be discovered by mass spectrometry-based proteomic studies in well-defined patient populations. Herein is described the advantages of using urinary exosomes as a starting material for biomarker discovery. In addition, the purpose of this review is to present an overall strategy for biomarker discovery in urine using exosomes and for developing cost-effective clinical assays for these biomarkers, which can potentially be used for early detection of disease, as a means of differential diagnosis, or as a means of guiding therapy. Finally, potential barriers that need to be overcome before urinary proteomics can be applied clinically, are emphasized.
authors.affiliation: Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1603, USA.
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
authors.forename: Trairak
authors.initials: T
authors.lastname: Pisitkun
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.forename: Peter
authors.initials: P
authors.lastname: Gross
authors.forename: Joergen
authors.initials: J
authors.lastname: Frokiaer
authors.forename: Nam Sun
authors.initials: NS
authors.lastname: Wang
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Gonzales
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
authors.forename: Mark A
authors.initials: MA
authors.lastname: Knepper
mesh_terms: D015415:Biomarkers / Q000652:urine*; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000652:urine*; D040901:Proteomics / Q000639:trends*; D014556:Urine / Q000737:chemistry
chemical_list: D015415:Biomarkers