[Mechanism of reduction in proteinuria by cyclosporine A: effects on the glomerular anionic sites].
To consider the mechanism of reduction of proteinuria by cyclosporine A (CYA) in the patient with intractable nephrotic syndrome, the effect of CYA on proteinuria and anionic sites (AS) of the glomerular basement membrane (GBM) was studied in puromycin aminonucleoside (PA) nephrotic rats. In addition the rats exogenously given human recombinant interleukin-2 (hrIL-2) every day repeated the same proteinuria were used. The PA nephrotic rats were made by single injection of PA 150 mg/kg excrete of urinary protein as compared 10 mg/day of urinary protein in the controls. The increase of urinary protein in the PA rats was inhibited by CYA10-20 mg/kg administrated orally from the day of PA injection for 15 days. To evaluate AS, the kidney were treated with a polyethyleneimine (PEI) staining method and the deposits in the lamina rara externa (LRE) of the GBM were counted on the electron micrographs. On the 15th day, in the PA rats, AS decreased greatly but were normal in the CYA-treated rats. On one hand, rats injected of hr IL-2 2.5 X 10(5)U/rat intraperitoneally for 14 days showed slight proteinuria on the 14th day, and the proteinuria was also inhibited by oral administration of CYA 25 mg/kg. As reduced in the rats treated with hrIL-2 as well as PA. The findings indicate that the proteinuria in the PA nephrotic rats and rats treated with hrIL-2 might result from reduction of AS and that the improvement of proteinuria in these rats by CYA might be due to the recovery of AS in the GBM.
Tanabe
T
T
Second Department of Internal Medicine, Hokkaido University School of Medicine, Japan.
D000818:Animals; D000838:Anions; D001485:Basement Membrane / Q000378:metabolism; D003524:Cyclosporins / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D009402:Nephrosis, Lipoid / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology; D011692:Puromycin Aminonucleoside; D051381:Rats; D011919:Rats, Inbred Strains
D000838:Anions; D003524:Cyclosporins; D011692:Puromycin Aminonucleoside