The potential benefits of rapamycin on renal function, tolerance, fibrosis, and malignancy following transplantation.
Use of the mammalian target of rapamycin (mTOR) inhibitor rapamycin in organ transplantation has evolved through different phases over the past two decades. After its discovery in the mid 1970s, antifungal and cytotoxic effects were the first of its properties to be explored, but the most significant advancement was found in its use as an immunosuppressive agent to reduce transplant rejection. This was viewed as an important step forward for immunosuppression, as early studies suggested that rapamycin was less nephrotoxic than calcineurin inhibitors (CNIs). Later, detrimental effects of rapamycin on kidney function were found in some patients. Nonetheless, a fascination with the mTOR pathway and its central role in multiple cellular processes has ensued. Among the potential positive clinically relevant effects is rapamycin's capacity to interfere with fibrotic processes that often accompany transplant rejection, and to influence the preferential development of immunological tolerance. A feature of increasing importance is that the mTOR pathway is central for vital aspects of tumor development, including angiogenesis and cell growth; rapamycin, therefore, has anticancer activities, which may prove critical in the fight against high cancer rates in transplant recipients. The final chapters defining the value of rapamycin have not been written yet, and indeed remain a work in progress. Only further research will reveal the full potential of rapamycin in organ transplantation.
Geissler
Edward K
EK
Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany. edward.geissler@klinik.uni-regensburg.de
Schlitt
Hans J
HJ
D000818:Animals; D005355:Fibrosis; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009369:Neoplasms / Q000209:etiology / Q000517:prevention & control*; D016377:Organ Transplantation / Q000009:adverse effects*; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D023001:Transplantation Tolerance / Q000187:drug effects*
D007166:Immunosuppressive Agents; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus