Chronic rejection, the principal cause of late renal allograft failure, has been correlated with multiple factors; one of the more important is adequacy of maintenance immunosuppression. Despite our extensive experience with cyclosporine A (CsA)-based contemporary immunosuppression, the optimal mix of adjunctive agents and the optimal dosage of CsA itself are not yet known. A review of CsA-based double and triple drug protocols, emphasizing maintenance therapy, raised questions about the necessity of steroids in all patients and the routine use of azathioprine in triple therapy. Recent analyses suggest that late graft dysfunction and loss may be related to chronic CsA underdosing; this impression is supported by studies confirming the long-term safety and improved efficacy of higher CsA dosages.
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