Applications
By virtue of organ tissue perfusion, blood plasma is the most generally useful material for the discovery of markers of human disease. However, the relatively high concentration of plasma proteins, as well as their wide concentration range, spanning at least nine orders of magnitude, often limit the study of blood biomarkers. Of the human body fluids amenable to routine clinical evaluation, urine has the advantage of being obtained frequently and non-invasively. It is relatively abundant, and as a result of being a filtrate of plasma, relatively simple in composition. Indeed, the use of urine for the discovery of markers of human disease dates to antiquity, when physicians used urine to diagnose diabetes mellitus. Furthermore, studies of urine may permit the detection of molecular species that are rapidly eliminated from blood circulation by virtue of their biological properties, such as hormones and cytokines, and therefore difficult to detect in blood plasma.
Methods to profile urine with increasing depth reaching several thousands of unique peptides and proteins have been applied to discover markers of a variety of common and rare diseases, involving both the urogenital tract, as well as distal organs, whose proteins are filtered from blood plasma. Specific investigations have uncovered novel markers of renal transplant rejection, acute kidney injury, nephritis, nephrotic syndrome, diabetic nephropathy, and ureteropelvic junction obstruction. Likewise, urine proteomic studies have described markers of bladder carcinoma, cystitis, and prostate carcinoma.
Urine proteomics has also been applied to the discovery of markers of non-urogenital disease, including coronary artery disease, ovarian cancer, pre-eclampsia, and pancreatitis. Approximately 10% of proteins detected by deep profiling of the human urinary proteome using physicochemical protein capture and LC-MS/MS have no reported expression in the urogenital tract, suggesting that they are likely found in urine as a result of filtration from blood plasma. This enables far-reaching studies to aid the diagnosis, improve stratification of therapy, and identify novel therapeutic targets for a variety of childhood and adult diseases.