PMID- 17100699
OWN - NLM
STAT- MEDLINE
DCOM- 20070426
LR  - 20220310
IS  - 0902-0063 (Print)
IS  - 0902-0063 (Linking)
VI  - 20 Suppl 17
DP  - 2006
TI  - The role and value of sirolimus administration in kidney and liver 
      transplantation.
PG  - 30-43
AB  - Enormous advancements in visceral transplantation have led to significant 
      improvements in the quality of life of patients. However, despite these 
      developments, the average graft half-life after transplantation has remained 
      almost unchanged and chronic rejection is still considered a major problem. In 
      this regard, more concerns have shifted to factors influencing long-term graft 
      survival, patient survival, and quality of life. To achieve this goal, 
      detrimental effects of immunosuppressive (IS) agents, which have deleterious 
      influence on the quality of life and/or patient survival, should be reduced. In 
      the course of recent years, the transplant community has worked on reducing these 
      side effects by developing new ISs, employing new combination regimens, or 
      finding and adjusting optimal dosages and blood level concentrations. Among the 
      IS agents, the antifungal, antitumoral and IS activity of mammalian target of 
      rapamycin (mTOR) inhibitors without nephrotoxicity, have received special 
      attention regarding this new class of IS. Sirolimus (SRL), as the first member of 
      mTOR inhibitors, has been utilized in many clinical trials with respect to its 
      benefit-risk assessment. In our review, the clinical evolution of SRL, as well as 
      the evidence-based clinical benefits of SRL in kidney and liver transplantation 
      (KTx, LTx), are summarized. Various studies of SRL in KTx and LTx have shown that 
      combination therapy with SRL will enrich the variety of IS modalities. It also 
      can be regarded as a safe base therapy to which other necessary drugs can be 
      added. In addition to the enhanced acute rejection prophylaxis, and in contrast 
      to the calcineurin inhibitors (CNI) and steroids, this drug solely does not have 
      common side effects such as nephrotoxicity, neurotoxicity, diabetes mellitus and 
      hypertension. Moreover, this agent might diminish vasculopathic processes that 
      mediate chronic allograft nephropathy (CAN). Therefore, by reducing the 
      likelihood of CAN it can decrease the rate of long-term organ failure. One 
      possibly desirable characteristic of SRL is its antiproliferative effect, which 
      could provoke antitumoral or antiatherogenic activity following transplantation. 
      Despite all promising impacts of SRL in organ transplantation, there are some 
      concerns regarding the adverse effects of this drug, for instance dyslipidemia, 
      pneumonitis and wound healing problems. However, the majority of these side 
      effects can be reduced or ceased by careful dose adjustments and correct timing 
      of use. In conclusion, after a decade of both in vivo and in vitro studies on 
      SRL, it can be advocated that SRL is a promising, potent and effective IS agent 
      as it reduces the rate of acute rejection episodes in de novo transplants. It 
      could improve the quality of life, graft and patient survival rate, and achieve 
      excellent outcomes with few adverse effects when wisely used in combination with 
      other immunosuppressants.
FAU - Mehrabi, A
AU  - Mehrabi A
AD  - Department of General, Visceral and Transplantation Surgery, University of 
      Heidelberg, Heidelberg, Germany. arianeb_mehrabi@med.uni-heidelberg.de
FAU - Fonouni, H
AU  - Fonouni H
FAU - Kashfi, A
AU  - Kashfi A
FAU - Schmied, B M
AU  - Schmied BM
FAU - Morath, Ch
AU  - Morath Ch
FAU - Sadeghi, M
AU  - Sadeghi M
FAU - Schemmer, P
AU  - Schemmer P
FAU - Encke, J
AU  - Encke J
FAU - Sauer, P
AU  - Sauer P
FAU - Zeier, M
AU  - Zeier M
FAU - Weitz, J
AU  - Weitz J
FAU - Buchler, M W
AU  - Buchler MW
FAU - Schmidt, J
AU  - Schmidt J
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Denmark
TA  - Clin Transplant
JT  - Clinical transplantation
JID - 8710240
RN  - 0 (Immunosuppressive Agents)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Graft Rejection/*prevention & control
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage
MH  - *Kidney Transplantation
MH  - *Liver Transplantation
MH  - Sirolimus/*administration & dosage
RF  - 58
EDAT- 2006/11/15 09:00
MHDA- 2007/04/27 09:00
CRDT- 2006/11/15 09:00
PHST- 2006/11/15 09:00 [pubmed]
PHST- 2007/04/27 09:00 [medline]
PHST- 2006/11/15 09:00 [entrez]
AID - CTR598 [pii]
AID - 10.1111/j.1399-0012.2006.00598.x [doi]
PST - ppublish
SO  - Clin Transplant. 2006;20 Suppl 17:30-43. doi: 10.1111/j.1399-0012.2006.00598.x.