• Overview

• It is the most common type of transplantation performing.

– The first succesful kidney transplantation was a living donor transplant performed between identical twins in 1954 at Brigham hospital in Boston by Joseph Murray.

• After discovery of immunosuppressive agents in 1959 a successful transplantation performed between nonidentical twins ,siblings & non-sibling individuals. • It is one of the allografts or isograft & is a heterotopic graft.

• Candidate ages are between newborn and 70 years. • The graft can be taken from both cadavor(70%) ,and living donors(30%).

Types of Graft

• A) According to Genetic relationship between donor and recipient:
• 1-Autograft: Is tissue transfer within the same individual. • 2-Allograft(Homograft):Is organ or • tissue transfer between genetically • non identical members of the same • species.

• 3-Isograft: Is tissue transfer between genetically identical individuals (identical twins). • 4-Xenograft:Is tissue transfer between different species.

• B) According to Surgical Position:
• 1-Orthotopic:An old organ removed & the new one is placed in the same position. • 2-Heterotopic:The new graft is placed in a different position.

Factors affecting organ transplantation • I. Donor factors: • It include • the following: • Type of the organ.
• • • • Relation ship with the recipient. Degree of cross match with recipient. Cause of death of the cadaver.

Factors affecting organ transplantation • II. Recipient factor: This Includes:
• Immunological integrity. • Previous sensitization. • Absence of other disease affecting immune response. • Metabolic disease or other systemic disease. • Nutritional state. • Needs for other medication & patient compliance.

Indications of Renal Transplantation..
• Patients from newborn to 70 years of age with end-stage renal disease and on maintenance dialysis are typical candidates,patients with declining renal function that requiring dialysis are also candidates.

Indications of Renal Transplantation
• Common indications are:
• • • • • • • • • • Glomerulonephritis. Diabetic nephropathy. Pyelonephritis. Hypertensive nephrosclerosis. Obstructive uropathy. Renal vascular disease. Polycystic disease. Systemic lupus erythematosis. Analgesic nephropathy. Metabolic disease ( oxalosis, amyloid ).

Preparation for Renal Transplantation
• I.Recipient Preparation.
• A.Evaluation:

• 1.Systemic evaluation:
• Pulmonery:Chest radiogram,pulmonary function tests. • Cardiac:ECG,echocardiogram,stress test and cardiac catheterization. • Gastrointestinal:Upper gastrointestinal series,barium enema,endoscopy,ultrsound and liver function tests. • Immunological:Purified protein derivative(PPD),Rapid plasmin reagin(RPR),serology for hepatitis B & C,CMV,EBV,HIV & vaccination status.

Preparation for Renal Transplantation
• 2.Renal evaluation:
• Urinalysis & urine culture. • Bloob urea,serum creatinine, • creatinine clearance, ultrasuond, cystourethrogram, • Electrolyte(Na,K,Ca,Phosphate) • Renal angiography. • Renin level in refractory hypertention& parathyroid metabolism should be evaluated.

Preparation for Renal transplantation .
• II.Donor preparation:
• 1.Cadaver donor:
• The organs for transplantation are taken from individuals with brain death,decided by two physitians ,provided that: • 1-The body should normothermic. • 2-Depressant drugs must not be present. • 3-Apnea test must be negative. • 4-EEG & cerebral blood flow studies are optional. • While the cadaver donor being on ventilator ,evaluation should be done .

Preparation for Renal transplantation .
• Contraindication for kidney donation are:
• Evidence of primary renal disease,there should be reasonable urine output & normal blood urea & creatinine. • Presence of HIV & hepatitis B infection. • Active systemic sepis . • Presence of malignancy within thepast 5 years with the exception of low grade primary tumour of CNS,nonmelanotic tumour of skin & carcinoma in situ of the uterine cervix.

2-Living donor: Perioperative mortality is 0.03%

• A-Living unrelated donor: On average
shares no more genes with recipient than a cadaver donor. • B-Living related donor:Share substantial portion of their genomes with the recipient.

• • • •

Living donor must: 1-Have perfect health. 2-Have normal renal fnction. 3-Good candidatefor anesthesia & operative procedure.

• 4-Evaluation should be done: • a-ABO typing,tissue typing &cross match. • b-Complete history &examination. • c-Investigations:CXR,ECG,CBP,Sequential multiple analysis,24 hour creatinine clearance & protein. • Serology for hepatitis B,C,CMV,HIV,urinanalysis &PPD • Ultrasonography,I.V pyelogram,CT-scan & arteriography.

III.Immunological Compatibility Tests
• Immunological compatibility of the donor and recipient influences the outcome of transplantation • 1-ABO blood group compatibility: It is essential for all types of organ transplantation,permissible transplants are: • Group O donor to group O,A,B,AB recipient; • Group A donor to group A or AB recipient; • Group B donor to group B or AB recipient; • Group AB donor to group AB recipient. • There i9s no need to take account of rhesus(Rh) atigen compatibility in organ transplantation. •

• 2-HLA compatibility & matching:
• There are 2 classes of Human Leukocyte antigen(HLA); • A-HLA class I antigens comprise HLA-A ,-B & -C • B-HLA class II antigen comprise HLA-DR, -DP & DQ. • These 6 HLA are located on chromosome 6 ,the content of each chromosome 6 is haplotype,and all humans have 2of these chromosomes ,one from the mother and one from father, HLA are defined by tissue typing.

• Cross match compatibility must be perform between recipients sera and lymphocytes of the donor for the presence of cytotoxic antibodies directed against surface antigens(HLA) on the T & B-lymphocyte of the donor,results;

• 1-Positive cross match : is positive for the presence of preformed antidonor antibodies in the serum of the prospective recipient and precludes transplantation between that donor and the recipient.

• 2-A negative reaction : absence of antidonor antibody is mandatorr before transplantation • Traditionally, cross- matching is performed by complement-dependent lymphocytotoxicity,but now flow cytometric cross-matching become more widespread ,and more sensitive than cytotoxicity.

Immunosupressive therapy

.

• Immunoprophylaxis is started at the timr of transplantation and continued indefinitely(as maintenance therapy),for all renal transplants except for isografts.

• Immunosupressive agents:

• 1-Antiproliferative agents: Like Azathioprine
and Mycophenolate • Azathioprine is converted to 6-mercaptopurine in the liver which inhibit purine, mycophenolate after ingestion is converted to mycophenolic acid it also inhibit purine,because lymphocytes do not have asalvage pathway for purine metabolism, their ability to proliferate is selectively impaired.

• 2-Calcineurin blockers:Like Cyclosporin
& Tacrolimus; • Each of these agents binds within T-cell to a particular cytoplasmic proteun or immunophilin, the resulting immunophilindrug complex blocks the activity of calcineurin(ghosphatase) within the cytoplasm of T-cell.

• Steroids: Glucocorticoids have broad
anti-inflammatory & immunosupressive effects , generally they inhibit all types lymphocyte, because of their numerous side effects many centers attempts to withdraw steroids after one year of transplantation .

• 4-Antibody preparation:
• Antilymphocytic antibody preparations are either monoclonal antibody preparation or polyclonal preparation ALG or ALS which are directed against CD3 or CD25 IL-2 recepter on T-cells. • They are used for patients who are at particular risk of rejection for example highly sensitised and second-or third-time graft recipients.

• 5-Rapamycin:
• It is anewly discovered immunosupressive agent, it is a macrolide which binds within T-cell to FK binding protein,it interfer with intracellular signalling from the IL-2 recepter &arrests T-cell division in the G1 phase.

• Immunosupressive Regimens;
• Induction regimens; To avoid rejection & establish a
good graft function within the first 2 weeks of transplantation.It starts at the time of transplantation • Induction regimen use antilymphosyte sera ,intravenous steroid(methyleprednisolone) plus one of the Calcineurin inhibitors. • Maintenance therapy: It provides long term immunosuppression to prevent rejection • These regimens usually include two or three drugs sometimes a forth agent canbe added.

Maintainance Regimens are

.

• 1-Truple therapy(tree drugs): It is most commonly used specially in first year, it include a calcineurin blocker as a main agent with antiproliferative agent and steroids. • 2-Dual therapy (two drugs): It uses one of the calcineurin blockers plus antiproliferative agents .
– ).

• 3- Quadruple therapy (four drugs): For recipients judged to be at increased risk of rejection ( e.g. Highly sensitised recipienta and gragts with a poor HLA match) ,by adding antilymphocytic antibody to triple therapy. • 4-Monotherapy (one drug): Afew renal transplant unit use monotherapy with a calcineurin blocker and then add other agent only if needed to prevent rejection.

– Antirejection Regemins : • They are high-dose, short-term( < 3 weeks ) treatment aimed at reversing acute rejection episode. These regimen include high-dose (pulse) corticosteroid,typically methyleprednisolone , or antilymphosytic sera ( specially for recurent rejection

Transplantation Procedure • Removal of donor kidney: • 1-from a cadavor; While the cadavor is on ventilator,
the abdomenal organs are perfused chilled organ preservation solution via an aortic & portal cannula,this produces rapid cooling of organs ,additional surface cooling can be achieved by saline ice slush. • When the kidney has been taken it plased intwo sterile plastic bags & stored at 0-4C by immertion in ice. • A sample of donor spleen & mesenteric LN are obtained for determination of tissue type & cross match test.

• 2- From living donor; Undeer GA the kidney
is removed from donor & rapidly flushed with cold solution to render it cold and ischemic. • A donor kidney can be stored upto 40-48 hours for transplantation.

• Recipient operation: • Under GA ,through a curved incition in lower abdomen ; • Clear the external iliac vessels , lymph nodes &adipose tissue. • The best position for transplanted kidney is in iliac fossa to be near the bladder and to prevent avascular necrosis of the ureter. • Renal artery is anastomosed to external iliac artery and the vein to the external iliac vein &ureter is implanted into the bladder. • In small child receiving adult donor kidney ,.the abdomen is opened through a midline incision & the graft is placed ntra-abdomenally with anastomopsis of renal vessels to the aorta and vena cava.

Complications
• •
• • • • • • • • • • •

1-Complications of the Operation: A-Complication of anesthesia
B-General complication of operation. C-Specific Operative Complications: i- Vascular Complications: Occur in 3-5% A-Renal artery thrombosis B-Renal vein thrombosis C-renal artery stenosis Ii-Lymphocele (Perinephric lymph collection), < 5% ultrasound is diagnostic. Iii- Urological complications: Occur in < 10% Urine leakage Ureteric obstruction Ureteric infarction

B- Rejection
• Three main types:
Acute During first 6 month Chronic Months or years after operation Mediated by antibody & cell mediated effecror mechanism,vasculopathy Progressive may need retransplantation Biopsy Hyperacute Occur at time of operation Caused by recipients antibody against donor HLA Class I & ABO incompatibility Avoidable Diagnosis is clinical & Biopsy

Mediated by TLymphocyte & mononuclear infilteration Reversable by agressive immunotherapy Biopsy

Complicatios of immunotherapy • 1-Infection : Mainly opportunistic
• a- Viral; CMV ( reactivation or transmitted from donor), its common & present with high swinging fever, lethargy & leucopenia ,treatment is ganciclovir • HSV ( reactivation of latent infection),lead to mucocutaneous lesion,treatment acyclovir. • Varicella zoster •

• B- Bactetial : Usually occur during first month so neen perioperative antibiotic prophylaxis • Tuberculosis not uncommon • C- protozoal infection ; Pneumocystic carinii ,lead to respiratory symptoms, diagnosed by lung biopsy or bronchopulmonary lavage. • D- fungal infection can occur.

• 2- Malignancy : commonly • Non-Hodgkinis lymphoma ( Posttransplant lymphoprolifrative disease) mostly EBV.inducwed B-cell lymphoma. • Skin cancer ; occur in 50% of cases in 20 years after transplantation mostly SCC,BCC & melanoma • Kapasi s sarcoma may occur

Outcome after transplantation
• For cadaveric renal transplantation
• Gragt survival is 85% after 1 year • 65% after 5 years • Patients survival is >90% after 1 year • >80% after 5 years

• For Living related donor transplantation
• Graft survival is 90% after 1 year • 80% after 5 years • Graft survival after second transplantation is only marginally worse than first graft. •

Thank You

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