摘要:

Donor shortage remains a critical problem in transplantation. Good management of available donors is a high priority. The majority of donors are heart beating, brain dead cadaveric donors from whom multiple organs are procured for transplantation. Most of these cadaveric donors have significant physiologic defects, which are magnified after brain death. Expeditious correction of these defects is vital to good function of the organs after transplantation. Optimal donor management can also impact long term graft function. The other critical factor in organ procurement is a technically sound retrieval of donor organs. Anatomical variations and abnormalities must be diligently identified while performing an expeditious retrieval of the organs. Most retrieval procedures are performed on an emergency basis with teams from different transplant centers working together in unfamiliar operating conditions. Anesthetic management of the cadaveric donor is important since the brain dead donors are frequently unstable from a cardiovascular standpoint. Donor procurement is a highly complex procedure that is coordinated exquisitely by organ procurement agencies. Donor procurement is a cooperative endeavor, which contributes to the health of the recipients. The donor families view organ donation as the only good thing that comes out of an otherwise tragic incidence.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Two distinctly different methods are used for clinical kidney preservation: pulsatile perfusion and static storage. Pulsatile perfusion continuously delivers nutrients including oxygen to the organ at hypothermia (4° to 8°C). Static storage limits nutrient delivery, and the kidneys are stored without oxygen at 0° to 4°C. The superiority of each method has been continuously debated since about 1970. We show in this review that pulsatile perfusion is a better preservation method when judged on the basis of lower delayed graft function (DGF) rate (10 to 15% lower when compared to static storage). The reduction of DGF rates can lower the cost of renal transplantation significantly by reducing the length of hospital stay and eliminating the need for post-transplant dialysis, which is necessary for the transplanted kidney to regain life-supporting function. Furthermore, the trend is for greater late-term loss of the graft (5 to 10 years) in kidneys with DGF. Thus, pulsatile perfusion can contribute to greater long-term graft success and reduce the number of patients waiting for kidney transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Progress in transplant immunosuppression has occurred in recent years with the emergence of new chemical agents along with new monoclonal antibodies. In this review, recent works are described in tacrolimus/mycophenolate mofetil/sirolimus-based immunosuppression, and also in anti-IL2R monoclonal antibody-based induction. In the light of recent multicenter and single-center clinical trials, several lessons have been learned: less acute rejection, no amelioration of patient/graft survival at short term, and significant side effects are seen with these new agents. On the other hand, several issues need to be solved or confirmed in the future by designing new trials: Are surrogate or other end points for efficacy other than patient/graft survival needed? Will these new agents avoid induction therapy? Will these new agents allow further reduction or replacement of steroids? Could these new agents treat or prevent chronic graft dysfunction? Could the use of nephrotoxic calcineurin inhibitors be limited or avoided? Is individualization of immunosuppressive therapy feasible? In our view, new trials have raised more questions that they have answered. Answering those questions is an exciting challenge for the new millennium.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Despite the introduction of new immunosuppressive agents and excellent 1-year graft survival rates, acute and chronic rejection and a variety of side effects still result in significant morbidity and cost to transplant recipients and the health care system. The tremendous intra-and interindividual variability resulting from a failure to individualize immunosuppression is one of the major, and potentially modifiable, causes. With the introduction of the cyclosporine microemulsion formula, a new interest has risen in the use of limited sampling or single postdose concentration measurements instead of predose trough levels. Also, for tacrolimus, trough levels may not be optimal for monitoring and interest in limited sampling strategies for estimation of drug exposure is increasing. For mycophenolate mofetil, which is used as a fixed-dose drug in most centers, data are accumulating regarding the use of trough levels or area under the curve monitoring to optimize the therapy. Sirolimus, owing to its novel mechanism of action, acts synergistically and permits dose reduction of calcineurin inhibitors. In addition, sirolimus has a distinct side-effect profile. However, sirolimus is a critical-dose drug for which therapeutic drug monitoring strategies are being developed. Knowledge of the pharmacokinetic/pharmacodynamic interactions between immunosuppressive drugs, which behave as critical-dose drugs, is likely to help clinicians provide optimal immunosuppression to achieve not only excellent short-term but also superior long-term results with minimal toxicity.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The introduction of calcineurin inhibitors was an important breakthrough in organ transplantation mainly due to the reduction of rejection early after transplantation. However, calcineurin inhibitor nephrotoxicity has been one of the major clinical problems in the use of these immunosuppressants. The balance between preventing immunologic allograft failures and managing nephrotoxicity is still an issue. Calcineurin inhibitor reduction may entail the risk of acute and chronic rejection. Hence, in most instances these agents have been used at conventional doses, in the short and the long term after solid organ transplantation. The advent of novel potent xenobiotic immunosuppressants, such as mycophenolate mofetil or sirolimus, may counterbalance the calcineurin inhibitor dose reduction or elimination to avoid nephrotoxicity. Extreme reductions of calcineurin inhibitors after the introduction of mycophenolate (or sirolimus) result in improvement of renal function, a better control of arterial pressure, and amelioration in lipid profile, without an apparent increased risk of rejection. It is conceivable that such minimalist regimens might allow steroid withdrawal and eliminate any need to increase calcineurin inhibitors to prevent chronic rejection. A step forward would be the complete elimination of calcineurin inhibitors, and the allocation of patients to therapies based on mycophenolate or sirolimus, either with or without the concomitant use of steroids. The avoidance of calcineurin inhibitors and steroids might constitute the ideal non-nephrotoxic and less atherogenic immunosuppressive regimens, and in this regard some preliminary studies have been reported. However, the short-term and long-term benefits of these strategies should be assessed in prospective and controlled studies.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

As the molecular basis of the immune response is elucidated, the opportunities for intervention with agents with established sites of action increase. With conventional small molecular drugs, major sites of action have been identified, such as inhibition of calcineurin, target of rapapmycin, and inosine monophosphate dehydrogenase. However, relating these effects to the actions and toxicities of the drugs remains incomplete. The focus now is on further characterizing these important signaling pathways. The proteins targeting surface molecules such as CD3, CD40L, B7, and others are better understood. The accumulated experience with these interventions furthers our understanding of these agents and the human immune response. The failure of a promising agent in some trials may reveal an incomplete understanding of the targeted biologic processin vivo. Studies with gene knockout mice also help us better understand the roles of these molecules and the molecular basis of how these agents might work. Curr Opin Organ Transplant 2000, 5:268–275 © 2000 Lippincott Williams & Wilkins, Inc.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Intestinal transplantation is now considered a life-saving option for patients with intestinal failure. Progress in this field since it became clinical reality with tacrolimus-based immunosuppression has improved posttransplant mortality and morbidity. Though early outcome and 1-year survival data have improved, there is continuing graft and patient loss with time. Parenteral nutrition remains the mainstay of therapy for patients with intestinal failure. Parenteral nutrition–dependent patients who develop life-threatening complications of parenteral nutrition are the primary candidates for intestinal transplantation. It is hoped that indications are broadened as further advances in intestinal transplantation improve the outcome.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID