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• 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 non-
identical 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 immunophilin-
drug 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:
Hyperacute Acute Chronic

Occur at time of During first 6 month Months or years after


operation operation

Caused by recipients Mediated by T- Mediated by antibody &


antibody against Lymphocyte & cell mediated effecror
donor HLA Class I & mononuclear infilteration mechanism,vasculopathy
ABO incompatibility
Reversable by agressive Progressive may need
Avoidable immunotherapy retransplantation

Diagnosis is clinical & Biopsy Biopsy


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 ( Post-
transplant 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
GOODLUCK
‫سوثاس بؤ هةمووان‬

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