Urinary proteome in a snapshot: normal urine and glomerulonephritis

The analysis of the urinary proteome is a potential source of information regarding the kidney's physiopathology. A clear knowledge of the protein composition of normal urine is an essential prerequisite to looking at its pathology. Technological evolution in the field of proteomics (2-dimensional [2D] electrophoresis, equalization, mass spectrometry and exosomes) has greatly expanded the power of analysis, allowing the detection of almost 2,000 spots in normal urine, only a minor part of which has been characterized as isoforms of known proteins. The identity of most spots (80%) remains to be determined. The analysis of urine composition in nephrotic syndrome (glomerulosclerosis and membranous nephropathy) and in lupus nephritis is in progress, but has not yet furnished any relevant material. The unique exception is the presence of acidic components that suggests alteration of the charge selectivity properties of the glomerular wall in cases of heavy proteinuria. In lupus nephritis, prostaglandin-H2-isomerase and hepcidin have also been identified as activity biomarkers. Several overexpressed or underexpressed proteins have also been found in urine IgA nephropathy, but their specificity needs validation. Decreased levels of aquaporin 2 and of inter-a-trypsin-inhibitor heavy chain 4 have been associated, respectively, with hypertension and with a different response to angiotensin-converting enzyme inhibition in IgA nephropathy patients. From the present stage, mainly characterized by discovery of new proteins in urine, we should now proceed to their validation as biomarkers of diseases and possibly to clinical trials. Participation by basic scientists and clinicians together in projects launched by worldwide organizations is of vital importance.