Transplant Flashcards
What are the criteria for brainstem death (6)?
-Fixed unresponsive pupils
-Absent corneal reflex
-Absent ouculovestibular/caloric reflexes
-No response to supraorbital pressure
-No cough/gag reflex
-No respiratory efforts to hypercapnia (PaCO2 >6kPa or 6.5kPa if retainer)
Must also be normothermic, not sedated, all reversible circulatory, metabolic and endocrine disturbances excluded and reversible causes of apnoea exclude - in a patient who is comatosed with a known aetiology of irreversible brain damage
What is the most common complication after renal transplant?
Lymphocele - up to 50%
RAS 10% (thrombosis <1%)
Renal vein thrmobosis similar
Urine leak 10% (distinguish by measuring collection creatinine:serum creatinine)
Haemorrhage 1%
What is the most common side effect of cyclosporin?
Nephrotoxicity
Calcineurin inhibitor inhibits IL-2 and IFN-G – inhibits T cell activation
Also; hirsutism, gingival hyperplasia, tremor and hyperplasia
What mediates hyper acute rejection?
Preformed antibiodies within host
-Complement system activated by antigens
- neutrophils, endothelial and platelet activation
- inflammation scarring and ischaemia
Type 3 hypersensitivity reaction
Acute - type 2 hypersensitivity mediated by B cells
Chronic - Type 4 hypersensitivity mediated by humoral and cellular mechanisms
What is the most common side effect of azathioprine?
Pancytopenia (esp leukopenia)
Others include alopecia, <1% pancreatitis/hepatotoxicity
Prodrug of 6-mercaptopurine - inhibits purine synthesis
MMF is similar - but has less bone marrow suppression and lower rejection rates
What are the indications for pancreas organ transplantation?
Usually IDDM, 6% NIDDM
- ESRF
- Hypoglycaemic unawareness
- IDDM with uncontrolled ketoacidosis
Others
What are absolute contraindications to renal transplant (7)?
- Predicted survival < 5 years
- Incurable malignancy
- HIV (?not true)
- Severe CVS disease
- Predicted graft loss >50% at 1 year
- Anti-GBM antibody disease with circulating antibody
- Inability to comply with immunosuppressants
What proportion of patients are insulin independent at 1 year post pancreatic transplant?
82%
cf 14% after islet transplantation (injected into portal vein percutaneously)
How much liver can be removed from a healthy donor?
55-70% (regenerates to almost 100% function within 4-6 weeks)
Complications 10%, mortality 0-1%
What are the Milan Criteria for liver transplant?
For HCC
-Single tumour <5cm
-Up to 3 tumours all ≤3cm
-Single tumour 5-7cm stable over 6months
without major vessel or extra hepatic involvement
Which type of pancreas transplant has the best 1 year survival?
SPK 86%
PAK 80%
PTA 78%
Although complications and mortality higher with SPK
How is delayed graft function related to cold ischaemic time?
For every 6 hours, increases by 23%
Synergistic effect with Acute rejection - if both than 35% 5 year survival rate
Acute rejection more likely with DGF (37% vs 20%)
What are expanded criteria donors?
Donors with age >60 or
50-59 with vascular cormorbidities (hypertension, creatinine >133, death by ICH)
What is sirolimus?
Non-calcineurin (i.e. ciclosporin, tacrolimus) inhibitor immunosuppressant.
mammalian target of rapamycin (mTOR) inhibitor
also everolimus
lower nephrotoxicity/hypertension
What is Alemtuzumab?
anti-CD52 (all immune cells)
Often used with lyphmocyte depleting antibiodies in acute phase
What is the usual anti rejection protocol for renal transplants?
A Calcineurin inhibitor (Ciclosporin, Tacrolimus) or Sirolimus if intolerant
An anti proliferative drug (MMF, AZT)
Steroids
Probably should also have IL-2RA - Basiliximab, recently licensed and maybe anti-thymocyte globulin)
Which T-cell receptor binds to MHC-Class 1?
CD8- MHC Class 1 (A, B,C)
CD4 - MHC Class 2 (DP,DQ,DR)
Most important HLAs are DR > B >A, C
What are orthotopic and heterotopic transplants?
Orthotopic - normal anatomical site
Heterotopic - different
What are isograft, allograft and autografts?
Isograft - genetically identical (also syngeneic)
Allograft - same species, different genetically
Autograft - same individual
Which solid organ transplant is most commonly affected by vascular thrombosis?
Pancreas alone - 5-8%
In patients with blood group AB, what are the most important criteria for transplant?
Can receive any ABO,
therefore:
Living>DBD>DCD
then HLA
Rhesus is irrelevant
How frequently does acute rejection occur after a liver transplant?
Up to 40%, normally 7-10 days
Non specific features, obstructive jaundice, Banff schema
When might haematuria occur after a pancreatic transplant?
If there is a pancreaticoduodenocystostomy and Venus thrombosis occurs
What is the most common infection after a renal transplant?
UTI (30% in 3 months) - standard pathogens
What is the incidence of non melanomatous skin cancer after solid transplant?
45-75% at 20 years
Which virus is associated with Kaposi’s sarcoma?
HHV8
How is a renal transplant preserved after removal prior to transplantation?
Using University of Winsconsin solution at 4 degrees C
Cold ischaemic times of up to 20hours are well tolerated. Warm >20mins problematic
What is Encapsulating peritoneal sclerosis?
Intra-peritoneal fibrosis after PD
RF include duration, peritonitis and hypertonic glucose dialysate
If obstructive symptoms may need peritonectomy
What is the most common cause of a sudden loss of urine output after renal transplant?
Renal artery thrombosis
Renal vein thrombosis is more insidious with haematuria and pain
What is the histopathological finding of chronic liver rejection?
Paucity of bile ducts
How is acute rejection of liver transplant treated?
Steroids +/- polyclonal anti-T cell antibodies
Occurs in 30-50%
What is the characteristic complication of Tacrolimus treatment?
Diabetes (up to 50%)
What are the key factors in preventing rejection and improving liver graft survival?
-Short cold ischaemia
-Minimal size mismatch
-ABO matching (but may be overcome with rituximab!)
Avoid steatotic liver donors
What is the most common cause of liver transplantation in the UK?
Alcoholic liver disease
(?Hep C worlwide)
In children its primary biliary atresia
What are the most common causes of renal transplant?
Diabetes and Chronic Glomerulonephritis
What are the absolute and relative contraindications to organ donation?
Absolute
- nvCJD
- HIV
Relative
- disseminated malignancy
- melanoma (unless local and >5 yrs)
- treated malignancy <3 years (except NMSC)
-age >60
-Active TB
-active sepsis
-Hep B/C
What is the threshold for vessel diameter and creating of AV fistulae?
2mm - 16% 3 month patency below this, 76% above.
Start radiocephalic then brachiocephalic probably.
What are the advantages of a brachiocephalic over radiocephalic fistula?
Higher flow rates, easier to cannulate, quicker to mature
but lower long term patency, higher swelling and steal and arch stenosis
In patients with chronic liver disease, what are some cause of decompensation (6)?
Infection (UTI, pneumonia, SBP)
Hepatitis Flare
HCC
Portal vein thrombosis
Alcohol
Drug induced
(Cholangitis, Cancer)
What is the MELD score?
Composite score of 6-40 based on creatinine, bilirubin and INR predicts 3 month mortality
Can be used to triage transplant (?>16)
UKELD also used adds sodium - score above 49 (9% 1 year mortality) –> transplant
What criteria must be met before undertaking testing for brainstem death?
- in apnoeic coma, unconscious and dependent on ventilation
- known cause that could lead to brainstem death
- all possibilities of drug intoxication, temperature aberration and metabolic imbalances excluded
If ICH, SAH can be performed within 6 hours
If hypoxic brain injury 24 hours
How is testing for brainstem death conducted 1+5?
By two experienced clinicians, at least 1 consultant, not involved in transplant.
1) Apnoea testing - preoxygenate for 10 mins, disconnect vent until PaCO2>6.65 and observe for absence of respiratory efforts
2) CN testing
-Check for pupillary reflex
Afferent/direct (II - optic)
Efferent/consensual (III - oculomotor)
-Corneal reflex
Afferent (V - trigeminal/ophthlamic)
Efferent (VII - facial)
- Vestibulo-ocular reflex (irrigate with cold water - eyes should move away)
Afferent (VIII - vestibular)
Efferent (VI - abducens)
-Supraorbital pressure
Afferent (V - trigeminal)
Efferent (VII Facial)
- Gag reflex
Afferent (IX Glossopharyngeal)
Efferent (VII Facial)
- Dolls eye reflex (move side to side and see if eyes move - not mandatory)
Afferent (VIII vestibular)
Efferent (VI Abducens)
What are the criteria for withdrawal of tacrolimus/calcineurin inhibitors?
> 12 months post transplant
no episodes of acute rejection in last 3 months
no contraindications to MMF or antiproliferatives
biopsy demonstrating absence of cell/antibody mediate rejection
What are the causes of chronic transplant dysfunction (CTD)?
Prexisting - donor disease, injury at retrieval, ischaemia-reperfusion
Post transplant
-Immune mediated injury, rejection (acute/chronic)
-Recurrent GN
-Obstruction
-UTI
-Renal vascular stenosis
-Atheromatous disease
-Hypertension
-Calcineurin inhibitor toxicity
-BK virus nephropathy
-DM
What is the Childs Pugh score?
Combination of:
1) Encephalopathy
2) Ascites
3) Bilirubin
4) Albumin
5) PT
Childs Pugh A 5-6 points = least severe - 1 year survival 100%
Childs Pugh B 7-9 points = moderate severity - 80%
Childs Pugh C 10-15 points = most severe - 45%
Can only be A if only 1 mild abnormality - bili>34, alb<35, INR >1.7, ascites or encephalopathy
In whom should CMV prophylaxis be given?
- CMV neg, donor CMV positive
- if having T cell depleting antibodies for induction if either donor or recipient positive
Usually Valganciclovir within 10 days for 100 days.
What are optimal tacrolimus levels?
8-10ng/ml
What are the outcomes for liver transplant in the UK?
90% graft survival at 1 year
70-75% at 6 years - Cholestatic disease > HCV/malignant disease
What is the most common anatomic variants of liver anatomy?
Hiatt group 2: Replaced Left hepatic artery from LGA (9.7%)
Hiatt group 3: Replaced right hepatic artery from SMA (10.6%)
Traditional 75.7%
What is the most common cause of acute liver failure in the UK?
Paracetamol > Non-A-to-E-Hepatitis > other drugs >Viral
<10% of transplants
Which patients with paracetamol induced liver failure should be discussed with the liver unit? (6)
-pH<7.3 or HCO3<18
-INR>3 on D2 or >4 after
-Oliguria/AKI
-Altered level of consciousness
-Hypoglycaemia
-Lactate >4 unresponsive to fluids
What features of decompensation of CLD should warrant consideration of liver transplant?
-Jaundice
-Ascites
-Variceal haemorrhage
-Hepatic encephalopathy