Diagnostic significance of SDS-PAA-electrophoresis of urinary proteins: different forms of proteinuria and their correlation to renal diseases

Abstract

Different types of urinary protein excretion may be recognized by determination of the proteins molecular weight. Beside chromatography different electrophoretic procedures have been applied to urinary proteins to study the underlying renal disease. The various zone electrophoreses separate merely by surface charge, proteins however covered by sodium dodecyl sulfate (SDS) migrate according to their molecular radius. So by SDS-polyacrylamide electrophoresis (SDS-PAe) macromolecular proteinurias (Mr 60,000- greater than 300,000 daltons) due to glomerular damage may be distinguished from micromolecular forms (Mr 10,000-70,000 d) due to tubular dysfunction. By densitometric quantitation of the separated Ig and transferrin an index of the glomerular selectivity is obtained, i.e. the capacity of the glomerular system, to retain serum proteins of a Mr above 150,000 d. By this procedure proliferative and degenerative glomerulopathies may be distinguished from minimal change disease, focal glomerular sclerosis and early membranous nephropathy; serial determinations of this selectivity index in the latter two disease entities show a gradual deterioration of glomerular protein handling with time. A glomerular proteinuria of even "physiological" quantity has been proved as early sign of renal involvment in systemic diseases; it may be detected earlier as for example the retinopathy in juvenile diabetics. Micromolecular proteinurias also occur at least in two forms: the typical tubular proteinuria (MW 10,000-70,000 d) is associated with acute or chronic severe tubular dysfunction as in interstitial nephritis and acute kidney failure; rejection episodes of kidney transplants lead to transient tubular proteinurias, too. The second form of micromolecular proteinuria (Mr 40,000-70,000 d) has been found frequently in association with a glomerular in diabetic and hypertensive glomerulosclerosis. By measuring clearances of the microproteins, the proteinuria with this pattern could be established as form independant from glomerular and tubular proteinurias. The constancy of the two micromolecular proteinurias led to the hypothesis of at least two selective mechanism of tubular protein resorption. SDS-PAe additionally allows the differentiation of extrarenal proteinurias, as caused by overflow, paraproteins, postrenal Ig-secretion or bleeding etc. In comparing clinical and in part histological data of about 2,000 patients suffering from kidney diseases the analysis of urinary proteins by this method has been proved as valuable non-invasive tool for diagnosis and follow-up.