Glomerular and tubular membrane antigens reflecting cellular adaptation in human renal failure.

The excretion profiles of the following marker proteins of glomerular and tubular origin were studied in patients suffering from chronic renal disease (GN, N = 36, GFR: 8 to 120 ml/min/1.73 m2): angiotensinase A (ATA), a glomerular endothelial glycoprotein, tubular ala(-leu-gly)-amino-peptidase-M (APM), gamma-glutamyl transpeptidase (GGT), and the major brush border surface glycoprotein (SGP-antigen) of 240 kD. In addition, urinary excretion of proteins from kidney tissue and serum from 30 patients undergoing chronic hemodialysis (RCDT) were analyzed. Compared to the controls, ATA, APM and GGT activities were significantly higher in urine specimens of patients with GFR greater than 25 ml/min, whereas the urinary APM, GGT and SGP concentrations were decreased, and correlated with the GFR. Urinary GGT activity was negatively correlated with ATA activity but positively correlated with the decrease in GFR. Urine ATA activity of RCDT patients was higher compared to normal controls (2P = 0.001). Urinary excretion of serum proteins of RCDT patients, as assessed by SDS-polyacrylamide gel electrophoresis, disclosed heavy tubular proteinuria, indicating predominant tubular rather than glomerular alterations in handling of proteins. Histochemical evaluation of kidney sections from RCDT patients revealed clusters of hypertrophic nephrons with increased glomerular and tubular concentration of immunoreactive membrane proteins. However, there was a general decrease in renal cell-marker concentrations as observed by quantitative image analyses. These results indicate that renal injury is associated with a modulation in the synthesis of tubular and glomerular cell markers.