Comparative acute nephrotoxicity of FK-506 and ciclosporin in an isolated in situ autoperfused rat kidney model.
The acute hemodynamic effects of ciclosporin A (Cs-A; 40 and 20 mg/kg), FK506 (1.5 and 0.4 mg/kg), and their vehicles were studied in an in situ autoperfused rat kidney model. Cs-A (60 +/- 7 and 66 +/- 5% of the initial value, respectively; p < 0.05 vs. control group) and FK506 (89 +/- 3 and 77 +/- 3% of the initial value respectively; p < 0.05 vs. control group) induced a significant fall in renal blood flow. Cs-A significantly increased the renal vascular resistance, whereas FK506 had no effect. The glomerular filtration rate (inulin clearance) declined significantly in all groups. Cremophore and FK506 vehicle had no hemodynamic effect on the glomerular filtration rate. In our model, FK506 had less vasoactive effects on the renal hemodynamics than Cs-A.
Bagnis
C
C
Service de Néphrologie, Hôpital Pitié-Salpêtrière, Paris, France.
Deray
G
G
Dubois
M
M
Adabra
Y
Y
Jacquiaud
C
C
Jaudon
M C
MC
Jacobs
C
C
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D014677:Pharmaceutical Vehicles / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D016559:Tacrolimus / Q000633:toxicity*; D014655:Vascular Resistance / Q000187:drug effects
D007166:Immunosuppressive Agents; D014677:Pharmaceutical Vehicles; D016572:Cyclosporine; D016559:Tacrolimus