Is cyclosporine withdrawal a therapeutic option in renal transplant recipients with chronic allograft dysfunction?
Chronic allograft nephropathy (CAN), the leading cause of graft loss, is due to both immunologic and non-immunologic factors. Cyclosporine (CsA) nephrotoxicity is supposed to significantly contribute to CAN. It has been suggested recently that new commercially available immunosuppressive drugs, such as Mycophenolate Mofetil (MMF) and Sirolimus (SRL), may have properties that may prevent and possibly partly reverse chronic rejection, the alloantigen-dependent immune process of CAN. Thus, our group and others have studied the efficiency of a 2-step therapeutic approach including CsA withdrawal and use of non-nephrotoxic immunosuppressive drugs with properties against chronic rejection, such as MMF or SRL. In this review, we will successively analyze how mechanisms of CsA-related nephrotoxicity, histopathologic findings in CAN, animal models and clinical studies justify this therapeutic approach.
Ducloux
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Department of Nephrology, Dialysis and Renal Transplantation, CHU Saint Jacques, Besançon, France. ducloux@chu-besancon.fr
D065095:Calcineurin Inhibitors; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D006084:Graft Rejection / Q000209:etiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine