CME on Transplantation is dedicated to online CME conferences, courses and presentations (slides with voice over) on transplantation, given by local and international experts. Its mission is to keep you up-to-date with the most recent developments on transplantation.
"Chronic Kidney Disease in Heart, Liver and Lung Transplant Recipients" Dr. Akinlolu O. Ojo (biography) English - 2004-11-26 - 47 minutes
(34 slides)
Summary : The modern immunosuppressive era has resulted in a significantly increased life-expectancy for solid organ transplant recipients. However, as a result of this, combined with the nephrotoxic potential of calcineurin inhibitors (CNI), chronic kidney disease (CKD) is increasingly an increasingly common complication of solid organ transplantation. Here, Dr. Akinlolu Ojo reviews his findings on the incidence of CKD among non-renal transplant recipients in the UNOS transplant registry.
Are certain transplant populations at higher risk of CKD than others? What is the cost of CKD in our transplant patients? What is the contribution of CNI to the risk of CKD post-transplant and how can we alter the immunosuppressive regimen to reduce this risk? Dr. Ojo addresses these questions and more in this superb comprehensive review of one of the most important complications of transplantation today.
Learning objectives : After viewing this presentation, participants will be able to discuss:
• The incidence of chronic kidney disease (CKD) in different solid organ transplant populations
• The financial and morbidity and mortality cost of CKD
• The relative contribution of both pre- and post-transplant factors to the risk of CKD
• The effect of CNI elimination on renal dysfunction and CKD
Bernardini J, Piraino B, Kormos RL. Patient survival with renal replacement therapy in heart transplantation patients. ASAIO J. 1998 Sep-Oct;44(5):M546-8.
English J, Evan A, Houghton DC, Bennett WM. Cyclosporine-induced acute renal dysfunction in the rat. Evidence of arteriolar vasoconstriction with preservation of tubular function. Transplantation. 1987 Jul;44(1):135-41.
"Post-Transplant Diabetes Mellitus - Epidemiology, Treatment, Long-term Effects" Dr. Donald E. Hricik (biography) English - 2004-05-18 - 50 minutes
(38 slides)
Summary : Diabetes Mellitus has emerged as an independent risk factor for cardiovascular events in kidney transplant recipients, with cardiovascular disease being an important cause of death in kidney transplant recipients with functioning grafts. With 30% to 40% of kidney transplant patients being diabetic prior to transplantation and approximately 25% developing post-transplant diabetes mellitus (PTDM) at 3 years, the burden of diabetes on this patient population is quite large indeed.
In this presentation, Dr Hricik explores the epidemiology of diabetes in solid-organ transplant populations. Risk factors for the development of PTDM are presented and the role of different immunosuppressive drugs in the pathogenesis of PTDM in a number of sub-populations is discussed.
Dr. Hricik also discusses the natural history of PTDM as well as its multifaceted management.
Learning objectives : After viewing this presentation, participants will be able to discuss:
o The modifiable and non-modifiable risk factors for the development of PTDM.
o The role of specific immunosuppressive drugs in the pathogenesis of PTDM.
o The therapeutic options available for the treatment of PTDM.
Bibliographic references : Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993 Feb;16(2):434-44.
Aker S, Ivens K, Grabensee B, Heering P. Cardiovascular risk factors and diseases after renal transplantation. Int Urol Nephrol. 1998;30(6):777-88.
Sumrani NB, Delaney V, Ding ZK, Davis R, Daskalakis P, Friedman EA, Butt KM, Hong JH. Diabetes mellitus after renal transplantation in the cyclosporine era—an analysis of risk factors. Transplantation. 1991 Feb;51(2):343-7.
Hricik DE, Bartucci MR, Moir EJ, Mayes JT, Schulak JA. Effects of steroid withdrawal on posttransplant diabetes mellitus in cyclosporine-treated renal transplant recipients. Transplantation. 1991 Feb;51(2):374-7.
Fabrega AJ, Meslar P, Cohan J, Lash J, Pollak R. Long-term (24-month) follow-up of steroid withdrawal in renal allograft recipients with posttransplant diabetes mellitus. Transplantation. 1995 Dec 27;60(12):1612-4.
Boudreaux JP, McHugh L, Canafax DM, Ascher N, Sutherland DE, Payne W, Simmons RL, Najarian JS, Fryd DS. The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients. Transplantation. 1987 Sep;44(3):376-81.
Schwimmer J, Zand MS. Management of diabetes mellitus after solid organ transplantation. Graft. 2001;4:256-265.
Presentation
"Mechanisms of T and B Cell Tolerance" Dr. Anita S. Chong (biography) English - 2004-05-18 - 47 minutes
(27 slides)
Summary : As the demand for transplantation continues to outstrip the available supply of suitable donors, the achievement of sustained, robust allograft accommodation is increasingly important.
In this presentation, Dr. Anita Chong reviews the mechanisms of both T and B cell-mediated tolerance. The concepts of central and peripheral tolerance are introduced and the evidence for the four intrinsic mechanisms of peripheral T cell tolerance is presented.
Dr. Chong also discusses the importance of addressing B cell-mediated tolerance and the potential role of encapsulation strategies in achieving long-term allograft tolerance.
Learning objectives : After viewing this presentation, participants will be able to discuss:
• The definition of tolerance
• Central versus peripheral tolerance
• The four intrinsic mechanisms of peripheral T cell-mediated Tolerance
• B cell-mediated tolerance
• Encapsulation strategies in transplantation
Bibliographic references : Ildstad ST, Sachs DH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts. Nature. 1984 Jan 12-18;307(5947):168-70.
Sharabi Y, Sachs DH. Engraftment of allogeneic bone marrow following administration of anti-T cell monoclonal antibodies and low-dose irradiation. Transplant Proc. 1989 Feb;21(1 Pt 1):233-5.
Chan SY, DeBruyne LA, Goodman RE, Eichwald EJ, Bishop DK. In vivo depletion of CD8+ T cells results in Th2 cytokine production and alternate mechanisms of allograft rejection. Transplantation. 1995 Apr 27;59(8):1155-61.
Kang SM, Schneider DB, Lin Z, Hanahan D, Dichek DA, Stock PG, Baekkeskov S. Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med. 1997 Jul;3(7):738-43.
"Barriers to Transplant Tolerance" Dr. Laurence A. Turka (biography) English - 2004-05-18 - 44 minutes
(35 slides)
Summary : Despite recent successes in inducing allograft tolerance in animal models, robust sustained tolerance in clinical human populations remains elusive. Dr. Laurence Turka discusses why in this presentation on the immunologic barriers to transplant tolerance.
What is the role of different immunosuppressants in facilitating or hampering the induction of tolerance? What is the best way of reducing the alloreactive T cell mass?
Dr. Turka briefly reviews the molecular basis of leukocyte cellular signalling en route to delving into the immunological hurdles that have limited attempts to systematically and consistently induce acceptance of allograft tissues.
Centering his discussion on peripheral methods of inducing tolerance, Dr. Turka reviews the evidence for the effect of blocking the T cell co-stimulatory pathway. The importance of reducing the alloreactive T cell mass in a specific fashion is discussed. Moreover, Dr. Turka introduces his laboratory’s own work on homeostatic T cell proliferation as a barrier to tolerance, as well as the role of heterologous immunity in limiting the application of laboratory models of tolerance to human transplant populations.
Learning objectives : After viewing this presentation, participants will be able to discuss:
• Cell to cell interactions essential to T cell proliferation
• The effect of blockade of the co-stimulatory pathway on T cells
• The effect of cyclosporine on Tolerance Induction
• The effect of sirolimus on Tolerance Induction
• The effect of non-specific anti-lymphocyte therapy (eg. Campath®) on Tolerance Induction
• The concept of homeostatic proliferation and its effect on tolerance induction
• The concept of heterologous immunity and its effect on tolerance induction
"Emerging Infections: SARS and WNV" Dr. Atul Humar (biography) English - 2004-05-15 - 27 minutes
(41 slides)
Summary : Severe Acute Respiratory Syndrome (SARS) and West Nile Virus (WNV) represent special challenges in the transplant program which need to be met with appropriate precautions.
WNV may be acquired through transfusions, donors or may be community acquired from an infected mosquito (the most common route of infection in transplant patients). Patients should be educated on how to protect themselves, for example by wearing insect repellant and avoiding outdoor activities at dusk and dawn. Transplant recipients are at greater risk for severe disease due to WNV compared to the general population.
Dr. Humar also speaks about the SARS epidemic and the Toronto General Hospital experience in dealing with the recent outbreak. The SARS Coronavirus is spread primarily via droplets, and infection in transplant patients may result in rapid progression of disease and increased infectivity.
Learning objectives : -Routes of infection in transplant patients
-Risk of severe disease in transplant patients vs. the general population
-Measures to prevent infection
-Screening tools
-Adapting the transplant program to new infectious challenges
"Pathogenesis of T cell mediated rejection" Dr. Philip F. Halloran (biography) English - 2004-04-23 - 50 minutes
(57 slides)
Presentation
"Transplanting the sensitized patient" Pr. Denis Glotz (biography) English - 2004-02-28 - 32 minutes
(52 slides)
Summary : In this presentation Dr Glotz discusses aspects relating to transplantation of the sensitized patient, such as identifying patients at high risk for sensitization, and the use of desensitization protocols.
The presence of both anti-Class I and anti-Class II HLA antibodies pretransplant has been shown to reduce the 2 year graft survival rate in kidney transplant recipients (1). A potential cause of sensitization is blood transfusion associated with either transplantation or pregnancy (2). It is however possible to predict which patients will develop anti-HLA antibodies after transfusion, says Dr Glotz, by using the flow cytometry assay to detect low titre antibodies.
It has been shown that patients developing anti-idiotypic antibodies to anti-HLA antibodies have improved graft survival rates (3). Detection of anti-idiotypic antibodies in the patient can be done by mixing current and historical sera and observing the percent inhibition of anti-HLA antibody (4). Desensitization protocols are thus one option for increasing the chances of obtaining a transplant for the sensitized patient. It has been shown that administration of intravenous immunoglobulins causes a sustained decrease in the titre of anti-HLA antibodies (5), and Dr Glotz describes the studies done by his group (5, 6) and others using this type of protocol.
Learning objectives : The participant will learn about protocols using intravenous immunoglobulins against anti-HLA antibodies in the sensitized patient.
4. MacLeod AM, al-Muzairai IA, Innes A, Power DA, Stewart KN, Catto GR. "Modulation of lymphocytotoxic activity in highly sensitised patients by anti-idiotypic antibodies." Transplant Proc. 1989 Feb;21(1 Pt 1):756-7.
