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Nephrol Dial Transplant (1996) 11: 507-513
© 1996 European Renal Association-European Dialysis and Transplant Association

research-article

Prevention of cyclosporin nephrotoxicity with a platelet-activating factor (PAF) antagonist

C. Bagnis1, G. Deray1,, M. Dubois2, E. Pirotzky5, C. Jacquiaud3, W. Baghos1, B. Aupetit4, P. Braquet5 and C. Jacobs1

1Department of Nephrology, Hôpital Pitié Salpêtrière Paris 2INSERM, Ecole de Chirurgie Paris 3Department of Biochemistry, Hôpital Pitié-Salpêtrière Paris 4Department of Biochemistry, Faculté de Médecine Pitié-Salpêtrière Paris 5Institute Henri Beaufour Research Labs Les Ulis, France

Correspondence and offprint requests to: Correspondence and offprint requests to: G. Deray MD, Service de Néphrologie, Hôpital Pitié-Salpêtrière, 83, Boulevard de I'Hôpital, 75013 Paris, France

BACKGROUND.: Cyclosporin (CsA) is a potent immunosuppressive drug whose main side-effect is nephrotoxicity. In the kidney, CsA induces vasoconstriction with a decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistance (RVR). CsA enhances platelet-activating factor (PAF) synthesis in mesangial cells in vitro. PAF, a secondary mediator of anaphylaxis and inflammation, exhibits vasoactive properties in the kidney similar to those of CsA.

METHODS.: The in situ autoperfused rat kidney model was used to investigate whether PAF plays a role in the haemodynamic injury induced by CsA.

RESULTS.: In this model, CsA (40 mg/kg and 20 mg/kg i.v.) induced a significant decrease in RBF and in GFR and an increase in RVR. BN 52021, a potent and specific PAF antagonist (20 mg/kg i.v. bolus dose) induced a significant increase in GFR (137±32% of initial value, P<0.05). BN 52021 (20 and 10 mg/kg) also significantly prevented the decline in RBF and GFR induced by CsA.

CONCLUSIONS.: We have demonstrated that the PAF antagonist BN 52021 can minimize the alteration of renal function induced by CsA.

Keywords: cyclosporin; platelet-activating factors; haemodynamics


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