Transplant Flashcards
Pre-op workup for live kidney donor
- Psychological
- No coercion
- Aware of risks
- Informed consent of procedure, recovery - Workup
- Blood type X-match, HLA typing
- Hx, exam
- Cr, urinalysis
- Screening for infection (HIV, CMV, EBV, Hep B,C)
- Cancer screening up to date
- CTA or MRA of kidney, DMSA
- Comorbidity screen (HTN, T1DM or T2DM with end organ damage, BMI > 35)
Contraindications to transplant
Comorbidities
- Active infection
- Active malignancy
- Systemic disease (SLE, amyloid, antineutrophil disease)
Psychosocial factors
- Inability to give informed consent
- Non-compliance
- Major psychiatric illness
- Active drug abuse
Types of rejection
Hyperacute
- Occurs in first 24 horus
- Due to preformed antibodies to HLA or ABO groups
- Results in endothelial damage, thrombosis, ischaemia and loss of graft
- Reduced risk by ensuring well-matched donors and recipients
Acute (T cell mediated)
- days - months
- More common with HLA mismatch
- Donor antigens are presented on APC’s, leading to activation of CD4 and CD8 T cells
- Causes influx of inflammatory cells, activation of cytokines and induction of apoptosis
- Renal biopsies show interstitial inflammation, arteritis and tubulitis.
- Managed with immunosuppression titration, steroids, IVIG if B cells involved, basilixamab and anti-thymocyte golbulin
Chronic (B cell mediated)
- Occurs months- years later
- Mediated by antibodies and results in vascular changes over years
- Biopsy shows complement C4d in capillaries, tubular atrophy and intersitial fibrosis
Immunosuppressants
- Calcineurin inhibitors (tacrolimus, cyclosporin)
- Inhibit IL-2 by blocking calcineurin, which is an enzyme involved in IL2 production by T cells
- SE: DM, Lipids, nephrotoxicity, Hirsutism - M-Tor inhibitors (sirolimus, everolimus)
- Inhibit mTOR signalling pathway responsible for immune cell differentiation and proliferation
- SE: Poor wound healing, pneumonitis, thrombocytopenia - Purine synthesis inhibitors (mycophenylate, AZA, cyclophosphomide, MTX)
- Blocks purine synthesis in T cells to stop them proliferating
- Need to check TPMT levels prior to starting
- SE: Bone marrow suppression, GI symptoms - Glucocorticoids
- Dampen most cytokines, esp IL2
- Inhibits transcription of inflammatory mediators and activation of T cels
Phases of immunosuppression
- Induction
- Generally treated with IV glucocorticoids and IL2 Antibody - Maintenance - generally triple therapy
- Glucocorticoid
- Calcineurin inhibitor (usually tacrolimus)
- Purine inhibitor (usually mycophenyate)
- M-Tor inhibitors (sirolimus) usually only used if problem with another drugs
Side effects of immunosuppressants
Infection
- Common infections occur more frequently
- Bacterial
- Viral (CMV, HSV, HZV, varicella, polyoma virus)
- Protozoal (PCP pneumonia)
- Fungal (candida, aspergillus)
Metabolic
- T2DM
- Lipids
Malignancy
Skin Ca
- SCC and BCC mediated by reduced immune surveillance, direct oncogenic effect and oncogenic viruses
Viral mediated
- EBV mediated lymphoproliferative disease
- HPV anogenital or head and neck cancers
- Hepatitis - HCC
- MC polyomavirus - MErkel Cell
- HHV 8 - Kaposis sarcoma
Brain dead criteria
Irreversible cessation of all brain function
Conditions (7):
- Normothermic
- Normotensive
- Exclusion of dsedating drug effects
- Abscence of metabolic, electrolyte or endocrine abnormalities
- Intact neuromuscular function (EMG or peripheral nerve stimulation)
- Ability to test brainstem function (need one ear and one eye)
- Ability for apnoea testing
Declared dead if following occurs and confirmed by 2 trained clinicians
- Unresponsive coma (stimulating all 4 limbs, trunk and cranial nerves with no response to pain)
- Absence of brainstem reflexes (pupillary response, corneal reflex, vestibuloocular reflex, gag relex, coough reflex, pain response in CN5 distribution)
- Absence of respiratory centre function (take off ventilation and need CO2 to get > 60mmHg + pH < 7.3 on ABG with no spontaneous breathing)
- Irreversible clinical setting (CTA or 4-vessel angiography with DSA to show no intracranial blood flow)
Indications for liver transplant
Acute liver failure without raised ICP
Chronic liver failure due to:
- Alcohol
- Hepatitis B,C
- Fatty liver disease
- Metabolic disease (Wilsons, hemachromatosis, cystic fibrosis, glycogen storage disease)
- Inflammatory disease (PBC,PSC)
- Malignancy (HCC, cholangiocarcinoma)
- Caroli’s disease
Factors affecting success of renal transplant
Recipient factors
- Age
- Degree of renal failure (better prognosis if pre-dialysis)
- If previous transplant
- Systemic disease (IHD, diabetes)
- Comorbidities
- Compliance to immunosuppression/ follow-up
- PResence of anti-donor antibodies
Donor factors
- Age of donor
- Condition of kidney
- ABO or HLA mismatch
Technical/ institute factors
- Ischaemic time
- Operation length
- Operator/ institute experience
- Presence of thrombosis or embolus
- Quality of followup
- Immunosuppression type and compliance
- Stenting of ureter
Contra-indications to transplantation
Psychosocial factors
- Active psychiatric illness
- Active addiction
- Lack of social support
- Non-compliant behaviour
Medical factors
- Severe uncorrectable cardiorespiratory disease
- Active infection
- Active Malignancy (or within past 2 years)
- HIV/ AIDS
- Severe comorbidities
Complications of liver transplant
Early
- Reperfusion injury
- Primary non-function
- Haemorrahge
- Hepatic artery thrombosis
- Portal vein thrombosis
- Bile leak
- Acute rejection (livers dont get hyperacute rejection)
Late
- Biliary strictures
- Acute rejection
- Chronic rejection
- Infectious complications
- Malignancy
- Incisional hernia/ bowel obstruction
