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Submitted on May 1, 2006
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, MD 20892-1603
Corresponding Author: knepperm{at}nhlbi.nih.gov
A myriad of proteins and peptides can be identified in normal human urine. These derive from a variety of sources including glomerular filtration of blood plasma, cell sloughing, apoptosis, proteolytic cleavage of cell surface GPI-linked proteins, and secretion of exosomes by epithelial cells. Mass spectrometry-based approaches to urinary protein and peptide profiling can, in principle, reveal changes in excretion rates of specific proteins/ peptides that can have predictive value in the clinical arena, e.g. in the early diagnosis of disease, in classification of disease with regard to likely therapeutic responses, in assessment of prognosis, and in monitoring response to therapy. These approaches have potential value, not only in diseases of the kidney and urinary tract, but also in systemic diseases that are associated with circulating small-protein and peptide markers that can pass the glomerular filter. Most large-scale biomarker discovery studies reported thus far have used one of two approaches to identify proteins and peptides whose excretion in urine change in specific disease states: 1) 2-dimensional electrophoresis with mass spectrometric and/or immunochemical identification of proteins, and 2) top-down mass spectrometric methods (SELDI-TOF-MS and CE-MS). These studies have been chiefly in the areas of nephrology, urology, and oncology. We review these applications, focusing on two areas of progress, viz. in bladder cancer and in acute rejection of renal transplants. Progress has been limited so far. However, with the advent of powerful LC-MS/MS methods along with methods for quantifying LC-MS/MS output, there is hope for an accelerated discovery and validation of disease biomarkers in urine.
Revised on July 10, 2006
Accepted on July 12, 2006
Discovery of urinary biomarkers
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