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.