Sirolimus in renal transplantation.
Acute rejection episodes are now as low as 5-20% in the first year after renal transplantation; however, graft half-life has remained almost unchanged in the last decade. This statistic is mainly attributable to the side effects of immunosuppression, with loss of allografts due to the chronic allograft nephropathy that is a consequence of calcineurin inhibitor toxicity or hypertension. Patient death due to cardiovascular events, infections and malignancy also contribute to allograft loss. The introduction of the inhibitors of the mammalian target of rapamycin sirolimus and everolimus in renal transplantation has increased the repertoire of immunosuppressive protocols substantially. They have a different mode of action and a different side effect profile (i.e. lower nephrotoxicity, less hypertension and less neoplastic potential) than the calcineurin inhibitors. The inhibitors of the mammalian target of rapamycin therefore provide an especially promising alternative for the maintenance immunosuppression after renal transplantation. This overview provides a summary of the current literature on inhibitors of the mammalian target of rapamycin, with a special focus on sirolimus.
Morath
Christian
C
Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, 69120 Heidelberg, Germany. christian.morath@med.uni-heidelberg.de
Arns
Wolfgang
W
Schwenger
Vedat
V
Mehrabi
Arianeb
A
Fonouni
Hamidreza
H
Schmidt
Jan
J
Zeier
Martin
M
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068338:Everolimus; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000628:therapy; D016030:Kidney Transplantation / Q000379:methods*; D011494:Protein Kinases / Q000378:metabolism; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases; D014181:Transplantation Immunology; D023001:Transplantation Tolerance; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus