肾移植课件.ppt

1、Transplantation,Peng Zhang, Urology Department West China Hospital, Sichuan University,Acknowlegements,To Prof. Lu Yiping Prof. Wang jia Prof. Lin tao and Prof. Wang li To other Colleagues working on renal and liver transplantation,Dream of Paranoia Dream of excellent surgeon who wants to excel hims

2、elf. Dream of excellent scientist who believe nothing is impossible.,Transplantation is a Dream?,Contents,Basic concepts of transplantation Clinical Organ transplantation Renal Transplantation, RT Transplantation Immunology MHC and Tissue Matching Graft Rejection Immunosuppression,Definition of Tran

3、splantation,Implantation of “non-self” tissue into the body the process of taking cells, tissues, or organs called a graft (transplant), from one part or individual and placing them into another (usually different individual). donor : the individual who provides the graft. recipient or host: the ind

4、ividual who receives the graft.,Blood Transfusion First attempts were unsuccesful (MISMATCH) Discovery of blood groups (Red cell antigens) A-BLandsteiner 1900 RhLevine, Stetson 1939 Succesful transfusion = Transplantation Others: Bone, Tissue-engineering, etc Transplantation Organ Transplantation,Ty

5、pes,Autologous graft (autograft) : within an individual, autotransplantation Syngeneic graft (syngraft, isograft) : identical twins, isotransplantation Allogeneic graft (allograft, homograft) : non-identical, allotransplantation Xenogeneic graft (heterologous graft, heterograft) : between species, x

6、enotransplantation,Classification of Renal Transplantation,Auto-RT Cadaveric Allograft RT Living related Living Donor Living unrelated Xenograft RT (In experimental),Transplantation History,experimental kidney transplantation -1912 Alexis Carel-Nobel prize 1935 human kidney transplant in Russia - re

7、jection P.B. Medawar (1945) skin grafts Self skin accepted Relative not accepted ! What is the difference ? Immunologic mechanism A. Mitchison (1950) Lymphocytes are responsible for rejection,Transplantation History,Peter Gorer (1935) Identification of 4 group of genes for RBC Gorer and Gorge Snell

8、(1950) Group II antigens are responsible for rejection Major HistoCompatibility genes (HLA) Nobel prize 1980 George Snell 1954 Succesful kidney transplant between identical twins in Boston Peter Bent Brigham Hospital Joseph Murray 1991 Nobel prize,HISTORY OF THE RT,1933 First clinical RT (Voronov);

9、1954 First long-term successful RT (Twin); 1958 Discovery of HLA (Human Lym Antigen); 1959 Radiation be used for immunosuppression; 1961 Azathioprine (Aza); 1962 Prednisolone; Tissue Matching; 1966 Cross-Matching; Late 1960 Preservation the Kidney24hr ; 1972 First successful RT(LRD) in china; 1978 C

10、linical use of Cyclosporine(CsA).,Key factors for succesful transplantation,Knowledge of MHC haplotypes Effective immunosuppression Ability to identify and treat infections Available donors,Applications of allografting transplantation,The importance of transplantation:,Clinical Organ Transplantation

11、,Renal Transplantation,END STAGE RENAL DISEASES (ESRD),Definition: (1) Various causes; (2) Irreversible injury; (3) Functional failure. Morbidity Europe: 50/million; China: 90-100/million,Renal Transplantation,TREATMENT OF ESRD,DIALYSIS Chronic Ambulatory Peritoneal Dialysis (CAPD); Hemodialysis (HD

12、). KIDNEY TRANSPLANTATION,Renal Transplantation,Renal transplantation is associated with as survival benefit for patients with ESRD when compared to dialysis; Even marginal donor kidneys confer a significant survival advantage over maintenance dialysis. The preferred therapy for most of the Pts with

13、 ESRD; More cost- effective; Better survival; Better life quality.,Contraindicaiton,Active invasive infection; Active malignance; High probability of operative mortality; Unsuitable anatomic situation for technical success; Severe psychological or financial problem.,Pre-OP Selection,ABO Blood Group:

14、 Compatible; Cytotoxicity Test: Donor Lymphocyte Recipient Serum Cross matching Donor Lymphocyte Recipient Serum Donor Serum Recipients Lymphocyte Mixed Lymphocyte Culture Tissue typing (HLA),Operation,DONOR Living donor Nephrectomy via flank approach; Nephrectomy via Laparoscope.,Cadaveric Donor To

15、tal midline incision; in situ flashing: Euro-collins/UW solution; Bilateral radical nephrectomy. Low temperature preservation.,Potential Advantages of living versus cadaveric kidney donor,Better short-term result (about 95% versus 90 % 1-yr function); Better long-term results (half-life of 12-20 yr

16、versus 8-9 yr); More consistent early function and easy of management;,Potential Advantages of living versus cadaveric kidney donor,Avoidance of brain death stress; Minimal incidence of delayed graft function; Avoidance of long wait for cadaveric transplant;,Potential Advantages of living versus cad

17、averic kidney donor,Capacity of time transplantation for medical and personal convenience; Immunosuppressive regime may be less aggressive; Help relieve stress on national cadaver donor supply; Emotional gain to donor.,Potential disadvantages of live donation,Psychological stress to donor and family

18、; Inconvenience and risk of evaluation process (i.e., intravenous contrast); Operative mortality (about 1 in 2000 Pts.); Major post operative complications (about 2% of Pts.);,Potential disadvantages of live donation,Minor postoperative complications (up to 50% of Pts.); Long-term morbidity (possibl

19、e mild hyper-tention and proteinuria); Risk for traumatic injury to remaining kidney; Risk for unrecognized covert chronic renal disease.,Extraperitoneally in the contralateral iliac fossa via Gibson incision.,Recipient Operation,Why contralateral ?,RECIPIENT OPERATION,Blood Vessel Anastomosis: Dono

20、r renal V Recipientsexternal iliac V Donor renal A Recipients internal iliac A Ureter Anastomosis: Donor ureter Recipients bladder Anti-reflux anastomosis,Clinical phases of rejection,Hyperacute rejection (minutes to hours) Preexisting antibodies to donor HLA antigens Complement activation, macropha

21、ges Accelerated rejection Acute rejection (around 10 days to 30 days) Cellular mechanism (CD4, CD8, NK, Macrophages) Chronic rejection (months to years !) Mixed humoral and cellular mechanism CHRONIC REJECTION IS STILL HARD TO MANAGE !,Immunosuppression,Immunosuppresents play a very impor-tant role

22、in organ transplantation Immuosuppresents extremely increase the effect and the survival rate of organ transplantation,Immunosuppression,Immunosuppresents are a double - edged sword; the most important thing is to increase their positive effects, and in the same time decrease their side effects (i.e

23、., organ toxicity, infection, tumors, ect.).,Diagnosis of rejection,Symptom/Sign fever; urinary output ; graft tenderness; graft size ; hypertension,Laboratory Test,Serum creatine, SCr; Urinary creatine, Ucr; Color doppler scan; radiorenogram; Ateriogram; Biopsy: (1) Fine needle aspiration biopsy (F

24、NAB); (2) Core needle biopsy(CNB).,Treatment of kidney rejection,Hyperacute (Sometimes during the operation !) No therapy, usually results in graft failure kidney should be removed Acute (Most frequently in the first 4 weeks) BIOPSY ! Increase immunosuppression Increase steroid dose Increase cyclosp

25、orin (monitor serum level !) ATG, ALG, OKT3 Chronic ACE inhibitors, prostacyclin analog drugs Steroid, Imuran, Cellcept,Immunosuppressive therapy,Lifelong administration (allograft) Most of the drugs available are non-specific Common side effects of therapy: Infection Cancer Bone-marrow depression,I

26、mmunosuppression,Calcineurin Inhibitors (CNI) (CsA, FK506) Mycophenolate Mofetil (MMF) Steroids /Prednisone,Problems of Transplantation,There are not enough organs At least 150,000 patients in industrially developed countries badly need donor organs and tissues Every 14 minutes another name is added

27、 to the national transplant waiting list. About 16 people die because of the lack of available organs for transplant each day. Rejection: When the immune system of the host detects foreign graft tissue, it launches an attack, resulting in tissue rejection,Gene technology may as a solution,Gene techn

28、ology makes it possible to humanize the bred organs - the immune system identifies the organ as its own tissue. Immune system rejection is prevented,Gene technology offers the possibility to breed the desired organs in animals. Lack of organs is no longer a problem,From which animals are we able to transplant organs,1. The Chimpanzee: Its DNA sequence differs from ours by only 2%,2. The Baboon: Its organs are too small for a large adult human,3. The Pig: Surprisingly similar to our anatomy and physiology,Organ breeding: A transgenic animal carries a foreign gene