How should the immunosuppressive regimen be managed in patients with established chronic allograft failure?

Abstract

The above discussion permits some broad recommendations for immunosuppressive management in established CAN. It must be emphasized, however, that these recommendations are tentative. They are not based on carefully randomized prospective clinical trials, but largely on theoretical considerations, clinical experience, and non-randomized and often small retrospective studies several of which are published only in preliminary form. Patients should be apprised of the quality of the information upon which these treatment decisions are made and should be included in the decision-making process. These recommendations are made on the presumption that reversible causes of chronic graft dysfunction have been ruled out, and that the clinical diagnosis of CAN has been confirmed histologically whenever possible. 1. Intensification of CI dosage or switching from one preparation to another has not been shown to be beneficial and may lead to exaggeration of nephrotoxicity. 2. Consideration should be given to reduction or even discontinuation of CI therapy. Such a therapeutic maneuver requires careful follow-up to screen for episodes of deteriorating graft function. 3. Reduction of CI therapy is generally accompanied by addition of a non-nephrotoxic immunosuppressant, though it has not been firmly established that such addition is necessary. There is most experience with MMF in these circumstances, though rapamicin may be an appropriate alternative. 4. Introduction of a new immunosuppressive agent in previously immunosuppressed patients has potentially dangerous consequences. Patients should be monitored carefully, and consideration given to prophylaxis to prevent development of infectious complications. 5. High baseline doses of corticosteroids are not indicated. "Pulse" steroid therapy may be valuable for episodes of deteriorating function, but repeated treatment should be avoided. Ideally, use of pulse steroids in these circumstances should follow histologic confirmation of an element of acute rejection. 6. Since repeated pulse steroid therapy should be avoided, it is rarely indicated to repeatedly biopsy patients with established CAN. 7. If graft function continues to deteriorate despite the above measures, plans should be made to prepare for ESRD treatment options, and immunosuppression should be withdrawn in a stepwise fashion as when dialysis commences.