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TRANSPLANTATION Process of transferring an organ, tissue or cell from one place to another
ORGAN TRANSPLANT Surgical procedure in which a failing organ is replaced by a functioning one
3 MAIN CATEGORIES:
• 2 major classes
• 2 different mechanisms:
• Cellular Rejection
• Humoral Rejection
ALLORECOGNITION AND LYMPHOCYTE
ACTIVATION
INDUCTION PHASE
Starting immediately posttransplant, when
the risk of rejection is highest
MAINTENANCE
Usually starting within days posttransplant
and usually continuing for the life of the
graft and the recipient
INDUCTION PHASE
DEPLETING ANTIBODIES
• Rabbit antithymocyte globulin (Thymoglobulin)
• Total dose of 6mg/kg
• Causes a cytokine release syndrome
• Principal SE: fever, chills, arthralgia,
thrombocytopenia, leukopenia, and an increased
incidence of variety of infection
• Atgam – purified gamma globulin obtained by
immunizing horses with human thymocytes
• Results in rapid depletion of peripheral lymphocytes
INDUCTION PHASE
NONDEPLETING ANTIBODIES
• Basilximab (Simulect) – anti-CD25 monoclonal
antibody
• Powerful induction agent without added risk of
infection, malignanices, or other major side effects
• Alemtuzumab (Campath, Lemtrada) – anti-CD25
monoclonal antibody
• Causes cell death by complement-mediated cytoclysis,
antibody-mediated cytotoxicity, and apoptosis
• 1 dose (30mg) – depletes 99% of lymphocytes
• Causes significant cytokine release
• Risk of infection and posttransplant
lymphoproliferative disorders
CORTICOSTEROIDS
MAINTENANCE anemia
BELATACEPT
• Also known as LEA29Y
• SE: posttransplant lymphoproliferative disorder,
metabolic disorders, hypertension, neurotoxicity,
glucose abnormalities and adverse cosmetic
effects
RITUXIMAB
• Chimeric anti-CD25 (anti-B cells) monoclonal
HUMORAL REJECTION antibody
• Used as treatment of antibody-mediated
rejection and use in desentization protocols
BORTEZOMIB
• Proteasome inhibitor, approved for treating
multiple myeloma
ECULIZUMAB
• Blocks the activation of the terminal
complement cascade
• Useful to treat antibody-mediated rejection
and to desensitized patients pretransplant
• SE: infection (N. meningitides)
• Should be immunized at least 2 weeks before
INFECTION AND
MALIGNANCIES
EARLY
INFECTION • Occuring within 1 month posttransplant
• Differentiate between medical and surgical
infections
• Surgical infections – most common and
require expedient surgical intervention
• Liver and Pancreas recipient, most severe
• S/Sx: peritonitis, fever, hypotension, ileus,
abdominal pain
• Treatment: prompt return to the OR
• Localized infection or abscess – Percutaneous
drainage an antibiotics
• Medical infections – respiratory, urinary tract
and bloodstream infection
• Treatment should be aggressive
LATE
INFECTION • Primarily due to chronic immunosupression
• Etilogic agents:
• Herpesvirus – most common
• CMV – can be transmitted or reactivated
• Usually occur 3 to 6 months posttransplant or
during treatment for rejection
• Treatment: IV ganciclovir, reduction of
immunosuppression
• EBV – first line of treatment is to reduce
immunosuppresion
• Rituximab – advanced PTLD
• Invasive fungal infections – high risk after 6 months
posttransplant
• Blastomyces dermatidis
• Coccidoides immitis
• Histoplasma capsulatum
• Opportunistic infections
• Pneumocystis jiroveci
MALIGNANCIES
• 5-fold increased risk
• Kaposi’s sarcoma, nonmelanoma, skin cancer, non-
Hodgkin’s lymphoma, and cancer of the liver, anus, vulva
and lip
• Increased risk for melanoma, Hodgkin’s lymphoma, cancer of the
lung, kidney, colon, rectum, and pancreas
ORGAN PROCUREMENT AND
PRESERVATION
(DECEASED AND LIVING
DONORS)
DECEASED DONORS – determined by the cessation of both cardiac
and respiratory function
IMMUNOLOGIC PSYCHOSOCIAL
EVALUATION EVALUATION
ABSOLUTE
CONTRAINDICATION
• Active Infection
• Presence of Malignancy
• Active substance abuse
• Poorly controlled
psychiatric illness
MEDICAL EVALUATION
• Cardiovascular evaluation
• Diabetes and Hypertension
• Screen for presence of significant cardiac
conditions, prior history of CHF and coronary
interventions or valcular surgery
• Resting 12L-ECG
• Echocardiography
• Stress Test – for patients with no active cardiac
conditions but with risk factors
• Troponin T levels
MEDICAL EVALUATION
• Malignancies
• Untreated and/or active malignancies are absolute
contraindications, except:
• Nonmelanocytic skin cancer
• Incidental Renal cell CA at time of concurrent
nephrectomy and renal transplantation
• Undergone treatment
• low-grade tumors with low risk of recurrence –
wait at least 2 years after successful treatment
• Advanced stage or with high risk of recurrence –
delay at least 5 years
MEDICAL EVALUATION
• Infections
• Thorough history of infections and immunizations
• Vaccinations completed at least 4-6 weeks before kidney
transplant
• Splenectomy anticipated – immunize against encapsulated
organisms
• With history or residing in endemic areas serologic screening
with chest roentgenogram (fungal infections)
• Acute Viral Hepatitis – contraindication to kidney transplant
• Chronic viral hepatitis
• Obtain liver biopsy
• Consider combined liver-kidney transplant
MEDICAL EVALUATION
• Kidney Disease
• 3rd most common cause of graft loss – recurrence
of glomerular disease
• FSGS – investigate for posttransplant nephrotic
proteinuria
• Rescue plasmapheresis should be instituted
• Adjuvant therapy with Rituximab
• Hypercoagulability
• History of thrombotic events, repeated
miscarriage, family history of thrombophilia
SURGICAL EVALUATION
UROLOGIC EVALUATION
• VCUG and complete lower urinary tract evaluation
VASCULAR EVALUATION
• Potential implant sited for kidney graft: iliac vessels, aorta, and vena cava
• Abdominal CT scan or ultrasound
• Pulsatile intra-abdominal mass
• Diminished or absent peripheral pulses
• Claudication
• Rest pain
• Tissue loss in LE
IMMUNOLOGIC EVALUATION
• ABO blood typing and HLA typing required
• Panel-reactive antibody (PRA) assal – higher PRA level, higher risk
for a positive cross-matching
• Luminex technology – use HLA-coated fluorescent microbead and
flow cytometry
• Considered gold standard
PSYCHOSOCIAL EVALUATION
• Patients with uncontrolled psychiatric disorders are at a high risk for
concompliance with drug treatment, impaired cognitive function, and the
development of substance abuse
RECIPIENT OPERATION
• Usually transplanted heterotropically
• Right iliac fossa (retroperitoneal) –
ideal position
• Left iliac fossa – if pancreas transplant
is anticipated or if previous failed left
iliac kidney grafts
RECIPIENT OPERATION
ACUTE REJECTION
• Occurs in approximately 20%
• First line treatment: high dose corticosteroids → antilymphocyte therapy
• Maintenance immunosuppression: corticosteroid, tacrolimus, and mycophenolate
INTESTINAL AND
MULTIVISCERAL
TRANSPLANTATION
OBSTACLES:
• High immunogenicity caused by
its abundant lymphoid tissue
• Microbial colonization of the
intestine – risk of translocation
of pathogenic microorganisms
into the recipient’s circulation
INDICATIONS AND RECIPIENT SELECTION
• Irreversible intestine failure in combination with TPN
failure
• Intestinal failure, variables include:
• What part of the SI is absent
• Ileocecal valve involvement
• Previous ostomy
• Length of remaining colon
• TPN Failure
INDICATIONS AND RECIPIENT SELECTION
• Liver Failure
• Combined Liver-Intestine Transplant (Treatment of Choice)
• Multivisceral transplant (liver, pancreas, stomach,
duodenum, and/or SI)
• Child: Diffuse intestinal dysmotility syndrome
• Adult: Diffuse portomesenteric thrombosis, extensive intra-
abdominal desmoid disease encasing the main visceral
vascular structures with concurrent short gut
syndrome or massive abdominal trauma
INDICATIONS AND RECIPIENT SELECTION
SURGICAL
PROCEDURES
ISOLATED INTESTINE
TRANSPLANT
• Blood supply based on the arterial inflow
from the SMA and venous outflow from
the SMV
• Living Donor: 150 to 200 cm of donor’s
ileum on a vascular pedicle comprising the
ileocolic artery and vein
• Recipient Operation:
• Aterial inflow to the graft from recipient’s
infrarenal aorta
• Venous drainage – vis systemic or
portomesenteric drainage
COMBINED LIVER-INTESTINE
TRANSPLANT
02 Idiopathic dilated
myopathy
Early complications
• Pulmonary graft dysfunction
• Acute cellular or antibody-mediated rejection
• Right heart failure secondary to pulmonary
hypertension
• Infection
• Hemodynamic values monitored
POSTTRANSPLANT
• Immunosuppression to prevent CARE
rejection
• Both T-cell-mediated (cellular) and B-cell-
mediated (antibody-mediated) rejection
monitored
• Consists of 3 categories of medication
• Calcineurin inhibitor – usually Tacrolimus
or Cyclosporine
• Antiproliferative agent – MMF or AZA
• Corticosteroid – prednisone
• Assess for infection
POSTTRANSPLANT CARE
Late complications
• Acquired transplant vasculopathy
• Progressive renal failure
• Malignancies – skin cancer and PTLD
• Accelerated CAD – 3rd most common cause of
death posttransplant
• Can begin to develop as early as 1-year posttransplant
• Screening tests and recipient examination
annually after first year
LUNG
TRANSPLANTATION