Proteins and protein fragments in nephrotic syndrome: Clusters, specificity and mechanisms

Proteinuria is the hallmark of renal diseases and the characterization of the urinary protein composition may become an important source of information for diagnosis and research. So far, protein analysis in urine has been utilized for a generic individuation of site-specific defects (glomerular vs. tubular) but there is a need for an extension of proteomics to specific urinary biomarkers in selected clinical conditions. The identification of fragments of proteins in plasma and urine may increase the spectrum of urinary biomarkers. The unique speculative application so far proposed for protein fragments is nephrotic syndrome, and specifically focal segmental glomerulosclerosis, in which case they reflect intrinsic proteolysis occurring in plasma and represent surrogate biomarkers of the disease activity. Albumin is probably the most studied protein. Several of the albumin fragments present a peculiar distribution of the fingerprint peptide pattern containing both the N-terminal region and the C-terminal domain with a complete lack of any MS signals for the internal sequence region. Their characterization utilizing new strategies based on 2-D nondenaturing electrophoresis is now in progress. Studies on a direct characterization of proteases in plasma and urine will also define the participation of proteases to the genesis of renal diseases.