Transplantation Xiang Li, Urology Department West China Hospital, Sichuan University
Acknowlegement To Dr. Lu Yiping and Dr. Wang jia To other Colleagues working on renal and liver transplantation
Transplantation is a Dream? • Dream of Paranoia • Dream of excellent surgeon who wants to excel himself. • Dream of excellent scientist who believe nothing is impossible.
Can you imagine? Can you imagine? Can you imagine?
Contents • Basic concepts of transplantation • Clinical Organ transplantation • Renal Transplantation, RT • Transplantation Immunology • MHC and Tissue Matching • Graft Rejection • Immunosuppression
Definition of Transplantation • 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 individual who receives the graft.
Blood Transfusion • First attempts were unsuccesful (MISMATCH) • Discovery of blood groups (Red cell antigens) • A-B Landsteiner 1900 • Rh Levine, Stetson 1939 • Succesful transfusion = Transplantation • Others: Bone, Tissue-engineering, etc • Transplantation • Organ Transplantation
Classification of Renal Transplantation • Auto-RT Cadaveric • Allograft RTLiving 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 - rejection • 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 (~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); • 1954 First long-term successful RT(Twin); • 1958 Discovery of HLA(Human Lym Antigen); • 1959 Radiation be used for immunosupp- ression; • 1961 Azathioprine (Aza); • 1962 Prednisolone; Tissue Matching; • 1966 Cross-Matching; • Late 1960’ Preservation the Kidney>24hr ; • 1972 First successful RT(LRD) in china; • 1978 Clinical use of Cyclosporine(CsA).
Key factors for succesful transplantation • Knowledge of MHC haplotypes • Effective immunosuppression • Ability to identify and treat infections • Available donors
Clinical Organ Transplantation Liver Transplantation Renal Transplantation
LIVER TRANSPLANTATION • Indication: End stage liver diseases (ESLD) • Hepatic Disease to ESLD • Congenital malfomation; • Congenital liver metabolic disorders; • Acute liver failure; • Chronic liver failure: (1) Cirrhosis: Hepatitis B, Alcoholic; (2) Parasites: Hydatid disease of liver, ect. • liver malignance
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
TREATMENT OF ESRD • DIALYSIS Chronic Ambulatory Peritoneal Dialysis (CAPD); Hemodialysis (HD). • 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 ESRD; • More cost- effective; Better survival; Better life quality.
CONTRAINDICATION • 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:Compatible; • Cytotoxicity Test: Donor Lymphocyte Recipient Serum • Cross matching Donor Lymphocyte Recipient Serum Donor Serum Recipient’s Lymphocyte • Mixed Lymphocyte Culture • Tissue typing (HLA)
OPERATION DONOR (1)Living donor • Nephrectomy via flank approach; • Nephrectomy via Laparoscope.
(2) Cadaveric Donor • Total 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 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 cadaveric 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; • 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(possible mild hyper-tention and proteinuria); • Risk for traumatic injury to remaining kidney; • Risk for unrecognized covert chronic renal disease.
Recipient Operation Extraperitoneally in the contralateral iliac fossa via Gibson incision. Why contralateral ?
RECIPIENT OPERATION • Blood Vessel Anastomosis: • Donor renal V Recipient’sexternal iliac V • Donor renal A Recipient’s internal iliac A • Ureter Anastomosis: • Donor ureter Recipient’s bladder • Anti-reflux anastomosis
Clinical phases of rejection • Hyperacute rejection(minutes to hours) • Preexisting antibodies to donor HLA antigens • Complement activation, macrophages • 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 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., organ toxicity, infection, tumors, ect.).
Diagnosis of rejection Symptom/Sign • fever; • urinary output ; • graft tenderness; • graft size ; • hypertension; • myalgia/arthragia.
Laboratory Test • Serum creatine, SCr; • Urinary creatine, Ucr; • Color doppler scan; • radiorenogram; • Ateriogram; • Biopsy: (1) Fine needle aspiration biopsy (FNAB); (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 cyclosporin (monitor serum level !) • ATG, ALG, OKT3 • Chronic • ACE inhibitors, prostacyclin analog drugs • Steroid, Imuran, Cellcept
Histocompatibility Antigens • Major histocompatibility antigens • MHC class I molecules : almost all nucleated cells • MHC class II molecules : APCs, endothelium of renal arteries and glomeruli • Minor histocompatibility antigens : H-Y molecule