[Mediators involved in the nephrotoxicity of cyclosporin A].
Cyclosporin A-induced nephrotoxicity is a well known adverse effect but its mechanism remains unclear. The understanding of the toxicity mechanism is necessary since the new generation of immunosuppressant drugs (cyclosporin G, FK 506, rapamycin) demonstrates renal toxicity. A renal vasoconstriction occurs with the first administration of cyclosporin and involves several mediators (prostaglandins, renal sympathetic nerves, dopamine. NO, endothelin) which may explain the limited benefit of antagonists. Furthermore, the vasoconstriction explains only haemodynamic modifications and cannot explain histological lesions. New hypotheses involving an alternation of cellular calcium homeostasis suggest alternative investigations to elucidate cyclosporin A nephrotoxicity.
Simon
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N
Service Hospitalo-Universitaire de Pharmacologie, Université de Paris XII, Centre Hospitalier Intercommunal, Créteil, France.
Barré
J
J
Jolliet
P
P
Urien
S
S
Tillement
J P
JP
D000276:Adjuvants, Immunologic; D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced; D014661:Vasoconstriction / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D016572:Cyclosporine