MEDIATORS INVOLVED IN CYCLOSPORINE-A NEPH ROTOXICITY

Cyclosporin A-induced nephrotoxicity is a well known adverse effect bu r its mechanism remains unclear. The understanding of the toxicity mec hanism is necessary since the new generation of immunosuppressant drug s (cyclosporin G, FK 506, rapamycin) demonstrates renal toxicity. A re nal vasoconstriction occurs with the first administration of cyclospor in and involves several mediators (prostaglandins, renal sympathetic n erves, dopamine, NO, endothelin) which may explain the limited benefit of antagonists. Furthermore, the vasoconstriction explains only haemo dynamic modifications and cannot explain histological lesions. New hyp otheses involving an alteration of cellular calcium homeostasis sugges t alternative investigations to elucidate cyclosporin A nephrotoxicity .