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Real Doctors (Life Makers)  |  Clinical  |  Surgery & Surgical Subspecialities.  |  Calcineurin inhibitor in organ transplantation « previous next »
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Calcineurin inhibitor in organ transplantation
« on: /September/ 30, 2005, 12:56:42 PM »

Current Opinion in Organ Transplantation

Purpose of review: Advances in renal transplantation for the past decade have focused on diminishing rates of acute allograft rejection, which have fallen to less than 20% for most patients. This has come about primarily because of the effective rejection prophylaxis afforded by the calcineurin inhibitor drugs, cyclosporine and tacrolimus. Whereas low rates of acute rejection have provided for excellent 1-year survival rates greater than 90%, there has not been an associated prolongation of graft survival 5 years and beyond. One potentially controllable factor that contributes to late graft loss is the progressive scarring of kidneys, termed chronic allograft nephropathy.

Recent findings: Unfortunately, calcineurin inhibitor drugs themselves cause progressive renal injury and contribute to chronic allograft nephropathy. In fact, histologic evidence for the progression of chronic allograft nephropathy can be demonstrated while kidney function remains in a fairly normal range. The recent introduction of a new class of immunosuppressive agents, the inhibitors of the mammalian target of rapamycin, may provide an opportunity for the development of regimens absent drug-induced nephrotoxicity. The unique combination of antibody induction followed by sirolimus, mycophenolate mofetil, and steroids for maintenance can be demonstrated to preserve renal structure and function as long as 2 to 3 years after transplantation in comparison with regimens based on calcineurin inhibitor drugs. This combination is also efficacious in animal models of chronic allograft nephropathy, but it produces some unique side effects that need to be considered.

Summary: Kidney transplantation without calcineurin inhibitor drugs can be safely performed with good results lasting as long as 2 to 3 years. Longer follow-up times will answer the question regarding the prevention of chronic allograft nephropathy and prolongation of graft survival

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