ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewIn 1995, BK virus (BKV) surfaced as a significant opportunistic pathogen, causing polyomavirus-associated nephropathy (PAN) in kidney transplant (KTX) recipients. This review, based on data published in 2002–2003, provides an update on the role of BKV in solid organ transplant (SOT) recipients.Recent findingsIn heart and liver transplant recipients, urinary BKV shedding and low-level viremia has been detected without disease. In solitary pancreas transplantation, one case of PAN has been identified among 4/38 (11%) of patients with BKV replication in the urine, which was associated with higher levels of tacrolimus. In KTX recipients, multiorgan failure due to vasculopathy and urothelial carcinoma represent exceptional manifestations of BKV disease. However, PAN is now recognized as a persisting complication affecting 1%–8% of KTX patients. Although the emergence of PAN coincided with the introduction of tacrolimus and mycophenolate into clinical practice, risk factors are not unequivocally defined. Reducing immunosuppression represents the primary mode of intervention, but validated intervention protocols are lacking. Screening for BKV replication in urine, plasma or protocol biopsies favors an earlier diagnosis of PAN with improved response to intervention. Case series using low-dose cidofovir show promising results, especially when combined with modified immunosuppression. Possibly, new immunosuppressive drugs with anti-proliferative or antiviral activity may enable interruption of the vicious circle of rejection and PAN. Retransplantation is an option in the management of PAN with recurrence documented in only 2/11 cases.SummaryBKV replication is frequently found in SOT recipients, but disease is largely limited to the kidneys. The preferential manifestation of PAN in KTX emphasizes the allo-situation in addition to immunosuppression. BKV screening of KTX patients is warranted to enable early intervention. Large prospective studies are needed to identify risk factors and to evaluate intervention strategies for PAN.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewCytomegalovirus is a major viral pathogen complicating organ transplantation. Recent advantages have been achieved through the development of new diagnostic technologies and use of antivirals. Cytomegalovirus-associated indirect effects, such as risk of rejection, transplant vasculopathy, and other infections, have been investigated.Recent findingsQuantitative molecular methods to monitor viral load, especially the new real-time polymerase chain reaction techniques, are commonly used to guide treatment of cytomegalovirus infections and preemptive therapy. Intravenous ganciclovir is the drug of choice for treatment of symptomatic infections, and its oral form is successfully used in prophylactic and preemptive regimens. High-dose acyclovir or its derivative valacyclovir is useful for prophylaxis of cytomegalovirus disease, and valganciclovir, a derivative of ganciclovir, is under clinical investigation. The criteria for cytomegalovirus infection and disease have been updated. Besides enhanced transplant vasculopathy, the indirect effects of cytomegalovirus—association with acute or chronic rejection—are suggestive but not conclusive. Involvement of cytomegalovirus in coronary artery remodeling is associated with the impaired ability of the vessel wall to enlarge in response to intimal increase. Alloresponse is involved in the pathogenesis of cytomegalovirus-enhanced chronic changes; chemokines play a major role in this process, as shown in animal models. Posttransplant recurrence of hepatitis C virus and concurrent activation of human herpesvirus-6 and human herpesvirus-7 are new associations of cytomegalovirus.SummaryAlthough new diagnostic techniques and prophylactic and preemptive therapies have made it easier to control the virus, cytomegalovirus infection remains a significant problem in transplantation. Further clinical investigation is needed to understand the indirect effects of cytomegalovirus.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewEpstein-Barr virus-driven posttransplant lymphoproliferative disorders remain a significant complication of solid organ transplantation. Routine monitoring of Epstein-Barr virus loads for detection and prevention of posttransplant lymphoproliferative disorders is now well accepted, whereas the range of therapies for the treatment of posttransplant lymphoproliferative disorders continues to grow. This article reviews recent progress in both areas, which have advanced the science and clinical management of Epstein-Barr virus-related posttransplant lymphoproliferative disorders.Recent findingsRecent studies continue to refine the understanding of Epstein-Barr virus loads and other markers to improve the specificity of posttransplant lymphoproliferative disorder prediction. Epstein-Barr virus-specific T-cell reactivity correlates with susceptibility to Epstein-Barr virus-driven posttransplant lymphoproliferative disorders in a complementary manner with viral loads, and may improve diagnostic accuracy. Other work examining reactivity to specific viral gene products and Epstein-Barr virus polymorphisms may aid in this determination. Advances in therapy of posttransplant lymphoproliferative disorders include the primary use of the anti-CD20 monoclonal antibody rituximab combined with antivirals and decreased immunosuppression, whereas preliminary data on the use of autologous or allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes suggest that they may have significant role in treatment. Improved chemotherapy regimens have also shown increased efficacy in the treatment of high-grade posttransplant lymphoproliferative disorder, which resembles B-cell lymphomas.SummaryAdvances in posttransplant lymphoproliferative disorders diagnosis and therapy have improved outcomes for solid organ transplant patients. Many of the new therapies, including cytotoxic T lymphocytes and rituximab, deserve larger, controlled trials to evaluate their effectiveness. Improvements in understanding of viral load and an increasing number of secondary markers should allow better prediction of who is at risk of progressing to posttransplant lymphoproliferative disorders and which patients would benefit from preventive algorithms.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThis review reports recent publications on parvovirus B19 infections in the transplant population.Recent findingsParvovirus B19 (B19) infections have been increasingly reported in the transplant literature and can cause a potential severe disease in transplant recipients. Diagnosis can be difficult in immunocompromised individuals and should ideally be screened for in the pretransplant period. Most recent publications focus on unusual presentations, such as persistent pure red blood cell anemia and neutropenia. However, glomerulopathy and liver or heart dysfunction have also been reported. The role of B19 in rejection remains unclear. Treatment of B19 infection after transplantation continues to include intravenous immunoglobulin and reduction or discontinuation of immunosuppression. New insights into treatment remain to be elucidated.SummaryParvovirus B19 continues to cause significant disease after transplantation. Multicenter trials would be advantageous in better defining the full range of clinical syndromes and optimal treatment strategies.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewFTY720, a synthetic myriocin analogue derived from culture filtrates ofIsaria sinclairii, is a novel immunosuppressant that in experimental animals, nonhuman primates, and renal transplant recipients produces lymphocytopenia and prolongs allograft survival in a dose-dependent fashion. Furthermore, the synergistic interactions of FTY720 promote the immunosuppressive effects of calcineurin antagonists and/or proliferation signal inhibitors, providing the possibility of reducing exposure to and thereby ameliorating the toxicity of these drugs.Recent findingsThe likely mechanism of action of FTY720 is induction of lymphocytopenia owing to migration from peripheral blood to secondary lymphoid structures. This mechanism involves binding to sphingosine-1-phosphate receptors on lymphocytes followed by involvement of the sphingosine transporter Abcb1 (Mdr1), the leukotriene C4transporter Abcc1, 5-lipoxygenase, and Rho. In humans, FTY720 reduces the incidence of acute rejection episodes and apparently produces only one significant toxicity: bradycardia. Phase III studies of FTY720 are ongoing to explore the potential advantages suggested by the results of earlier trials: high oral bioavailability, low interindividual variations in exposures at a constant dose, and the absence of collateral toxicities associated with other immunosuppressants (disturbed lipid metabolism, diabetes mellitus, nephrotoxicity, neurotoxicity, and myelosuppression).SummaryFTY720 is an archetype of a new class of agents that alter lymphocyte adhesion and migration and disrupt the participation of chemokines in inflammatory processes. FTY720 is likely to play an important future role by synergizing with other agents, yielding less toxic immunosuppressive regimens.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewRecent publications have focused on the results of multicenter trials and single-center reports detailing the use of Sirolimus (SRL) and Everolimus in organ transplantation and coronary artery disease. This review will define the current role of SRL.Recent findingsMulticenter randomized trials have demonstrated the efficacy of SRL in kidney and kidney–pancreas transplantation with minimization or elimination of cyclosporine, or, along low doses of tacrolimus. The efficacy of SRL–mycophenolate (MMF)–corticosteroids regimens in kidney transplantation has been demonstrated in single-center reports. In phase III trials, Everolimus is more efficacious than MMF and azathioprine in kidney and heart transplantation, respectively. Everolimus and Sirolimus–impregnated coronary artery stents have lower restenosis rates and a lower incidence of cardiac events than regular stents. Toxicities of SRL are concentration related, and improve with control of SRL levels. Hepatic artery thrombosis and bronchial anastomosis dehiscence are fatal complications needing further research.SummarySirolimus is being used more commonly as an immunosuppressive agent in all organ transplants. Everolimus is still awaiting Food and Drug Administration approval. This review describes the current role of Sirolimus, and use in combination with other immunosuppressive agents.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe rabbit polyclonal, antithymocyte, antibody Thymoglobulin is used as a potent T-cell depleting agent in immunosuppression for more than 30 years. New findings continuously expand our understanding of the immunopharmacology of Thymoglobulin and translate into novel therapeutic concepts.Recent findingsIn vitroandin vivostudies have shown that Thymoglobulin acts both in the blood and in secondary lymphoid organs. The action is rapid because the binding to cell surface molecules does not require new gene expression. Apoptotic cell death was identified as the main pathway for cell depletion in lymphoid organs. Functional cellular changes are primarily induced by modulation of cell surface antigens. The ability of Thymoglobulin to interfere with leukocyte–endothelium interactions by both downmodulating adhesion molecules and binding to chemokine receptors has recently been demonstrated. Significant depletion and modulation can both be achieved by short-term and high-dose regimens and are used now in induction therapies to effectively reduce immunosuppressive maintenance therapies. Long-term studies have shown characteristic changes associated with the short-term therapy persisting for years. These changes reflect age-dependent regeneration pathways and subset-specific kinetics.SummaryRecent studies provide new insights into the mechanisms of action unique to Thymoglobulin as a polyclonal antibody preparation. In particular, they identify the key role of drug-dosing regimens for the optimal use of nonspecific and specific immunomodulating actions.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe question addressed in the title of this paper iscontroversial because of the lack of clear data and conflicts due to the paucity of existing data. Therefore, the purpose of this review is to summarize some of the relevant clinical and experimental findings.Recent findingsIt has recently been suggested by a retrospective analysis of the United States Renal Data System data that mycophenolate mofetil (MMF) therapy is associated with a significant decrease in the relative risk of chronic allograft failure. Chronic allograft failure, however, may differ from a biopsy-proven chronic allograft nephropathy (CAN). MMF has been shown to inhibit antibody formation in animal models, and alloantibody does correlate with development of chronic allograft injury. Hence, there is compelling rationale to expect MMF therapy to decrease the incidence of chronic rejection of allografts in humans. Nevertheless, current data are only provocative and suggest a need for further direct study of this important question.SummaryIn summary, it is unclear at this time whether MMF has a direct salutary or deleterious effect on CAN in human renal transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewLeflunomide is a disease-modifying agent approved for use in rheumatoid arthritis and used off label for other conditions such as systemic lupus erythematosus. It has several properties that generate significant interest for potential use as an immunosuppressive agent in transplantation. This article reviews some of the properties stimulating this appeal and the initial reports on the use of leflunomide in transplantation, ending with a discussion of similar agents in development.Recent findingsIn cell models, leflunomide is able to limit both cellular and humoral immune responses. In animal allograft and xenograft models, leflunomide has demonstrated the ability to prevent or limit acute rejection and slow or reverse chronic rejection processes, independently or in synergy with other immunosuppressive agents. Leflunomide has demonstrated antiviral properties against pathogens of concern in transplant recipients and may have a quite favorable cardiovascular risk profile. Reported use of leflunomide in human transplantation is limited, but two recent reports, one prospective and one retrospective, describe the successful use of this agent in solid organ transplantation.SummaryLeflunomide has several properties that make it an excellent candidate for use in transplantation, but concerns about the prolonged half-life and potential for hepatotoxicity temper the enthusiasm. As it will likely be several years before similar, shorter acting agents are available, continued study is warranted to discern the appropriate use in human transplantation of this currently available agent.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID