Urinary Proteins of Tubular Origin: Basic Immunochemical and Clinical Aspects

Abstract

A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal β-N-acetyl-glucosaminidase (β-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, γ-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein ‘SGP-240’ and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cz’s-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both ‘soluble’ and high-molecular-weight membrane particles (vacuolar blebs, > 10⁶ dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular ‘histuria’ which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase.