12. The Urinary Proteomics: A Tool to Discover New and Potent Biomarkers for Kidney Damage

The increasing number of patients suffering from chronic renal failure represents one of the major challenges to which nephrologists are faced worldwide today. For a better therapeutic outcome of this disease earlier detection is urgently warranted in routine clinical practice. Urine is a kind of messenger of the urinary system function. Kidney damage or dysfunction results in release of peptides and proteins in urine (Figure 12.1.), this renders urine analyses of wide clinical interest for evaluation of kidney and urinary tract disorders. Urinary diagnostic can help to detect diseases that do not produce striking signs or symptoms at an earlier stage. Following parameter are routinely analysed for urine: method of collection, urine specific gravity, colour, turbidity, pH, glucose, ketones, bilirubin ictotest, blood and epithelial cells, and detection of proteins. Urinary proteins are of particular importance as their amount and composition reflect renal function and disorder (1). The estimation of protein amount in urine is of big importance for diagnostic as proteinuria is a marker for renal disfunction (2) and responsible for the progression of renal failure (3). Different methods were established to estimate the protein amount in urine, several of them found their way in routine diagnostic for evaluation of proteinuria. However, all these assays still not fulfil the conditions required for an adequate diagnostics. New techniques such as the analysis of the diseased renal proteome are highly promising to overcome some of these problems (4-9). Proteomics has enormous potential to improve the quality of urinproteins based diagnostic, as well as providing practical insights that will impact medical practice and therapy. Beside direct analysis of renal tissue, mass spectrometric approaches to urinary peptide/protein profiling are promising to have potential value in the none-invasive diagnosis, monitoring or prediction of renal and urinary tract diseases. Figure 12.1. Origin of urine proteins: in the urinary system high molecular weight proteins (> 40 kDa) are hold back in the glomerular part, whereas the low molecular weight proteins are absorbed in tubulus. Glomerular proteinuria led to increased release ... 12.2 Defining proteomics and clinical proteomics Proteomics is the systematic study of proteomes, which describes the entire protein content of one or all cells of an organism as ell as of bodily fluids such as blood, urine and sweat. While the genome of an organism is considered to be mostly static, the proteome shows dynamic properties with protein profiles changing in dependence of a variety of extra- and intracellular stimuli (i.e. cell cycle, temperature, differentiation, stress, apoptotic signals). Proteomics can be divided into three main areas: primarily, protein micro-characterization for large-scale identification of proteins and their post-translational modifications; secondly, differential display proteomics for comparisons of protein levels with potential application to a wide range of diseases; and thirdly studies of protein-protein interactions. Clinical proteomics is the part of proteomics that aims to characterize the interconnection between different tissues in organs or between organ and circulatory systems together, with clinical applications for diagnosis and therapy as ultimate target. Clinical proteomics include a large number of areas e.g. cancer proteomics, biomarker discovery, toxicoproteomics, pharmacoproteomics, stem cells proteomics, fluids proteomics… In clinical application, a comparative approach of normal and abnormal status of cells, tissues or bodily fluids is employed to identify proteins that exhibit quantitative changes in a disease-specific manner for use as diagnostic markers or therapeutic targets. Clinical proteomics still is a new promising analytic discipline with the following main aims: a) discovery of biomarkers allowing an early detection, risk management or therapeutic monitoring of diseases for the establishment of individualized treatment procedures, b) identification of protein targets for the development of new mechanistic intervention therapies with the promise of an improved clinical outcome.