Tissue plasminogen activator therapy of rabbit nephrotoxic nephritis.
To study the efficacy of tissue plasminogen activator (PA) therapy to prevent deteriorating renal function in experimental proliferative glomerulonephritis we used a model of nephrotoxic nephritis induced in rabbits by injection of antiglomerular basement membrane antiserum. Saline or recombinant tissue plasminogen activator (rt-PA, 1.3 mg/kg body weight) was infused daily for 7 days starting from day 7 after the injection of antiglomerular basement membrane antiserum when the disease had been already triggered. Animals were killed on day 14. Rabbits given saline had abundant deposits of fibrin and crescents in about 67% of glomeruli. rt-PA significantly protected animals from glomerular fibrin deposition and crescent formation with respect to saline-treated animals. Renal function measured as creatinine clearance was dramatically impaired in rabbits given saline. Treatment with rt-PA ameliorated the renal function impairment of nephrotoxic nephritis. rt-PA did not produce a systemic fibrinolytic state as indicated by alpha 2-antiplasmin level measurement. These results suggest that tissue PA may have important implications in preventing renal function deterioration in humans with crescentic glomerulonephritis and fibrin depositions.
Zoja
C
C
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
Corna
D
D
Macconi
D
D
Zilio
P
P
Bertani
T
T
Remuzzi
G
G
D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006400:Hematocrit; D006487:Hemostasis / Q000187:drug effects; D007106:Immune Sera; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use* / Q000633:toxicity; D000511:alpha-Macroglobulins / Q000378:metabolism
D007106:Immune Sera; D011994:Recombinant Proteins; D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; D003404:Creatinine; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin