Proximal tubule function in chronic serum sickness glomerulonephritis of rats.
Fatal immune complex glomerulonephritis can be induced in rats by chronic intravenous administration of bovine serum albumin. There are three distinct stages, mild, moderate, and severe, in the development of renal immunopathology and pathophysiology in this model of chronic serum sickness. The work described here was undertaken to evaluate aspects of proximal tubule function in those different stages. Tissue water distribution, oxidative metabolism, and transport of representative organic anions and cations were measured in renal cortical slices. In mild chronic serum sickness all functions were normal except the transport of p-aminohippurate (PAH, organic anion), which was significantly decreased. This decrease appeared to be attributable to immunization with Freund's adjuvant. In the moderate stage of chronic serum sickness, proximal tubule functions and morphology appeared essentially normal. Only Na-K-ATPase activity was somewhat lower than in controls. However, proximal tubule dysfunction was a feature of severe chronic serum sickness. A significant inhibition of anion and cation transport was observed. Reduction in transport functions occurred together with impaired oxidative metabolism and severe reduction in Na-K-ATPase activity. Abnormalities of mitochondrial structure, a decrease in number of mitochondria, and a significant increase in intracellular H2O content provided additional evidence of degenerative changes in proximal tubule cells during the severe stage of chronic serum sickness. It was concluded that decreased transport of organic ions by the basolateral membrane in proximal tubules of rats with severe chronic serum sickness resulted from a breakdown in the metabolic machinery of the tubule epithelium rather than a specific injury to organic ion transport systems.
Park
E K
EK
Hong
S K
SK
Andres
G
G
Noble
B
B
D000818:Animals; D002908:Chronic Disease; D005260:Female; D005455:Fluorescent Antibody Technique; D005620:Freund's Adjuvant; D005921:Glomerulonephritis / Q000503:physiopathology*; D005922:Glomerulonephritis, IGA / Q000473:pathology; D007105:Immune Complex Diseases / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000503:physiopathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew; D012710:Serum Albumin, Bovine; D010130:p-Aminohippuric Acid
D012710:Serum Albumin, Bovine; D005620:Freund's Adjuvant; D010130:p-Aminohippuric Acid