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
What UKELD score suggests a survival benefit to transplantation?
≥49
Some others also benefit e.g. PBC with intractable pruritus
In which situation can a non Milan criteria HCC be transplanted?
-5-7cm if no progression over 6 months
-HCCs downstaged with TACE etc
What are absolute contraindications to Liver Transplant?
- Predicted extra hepatic mortality >50% at 5 years
- Severe irreversible pulmonary disease
- Alcohol/drug misuse
- Active or previousextra-hepatic malignancy (exc neuroendocrine)
- Extrahepatic sepsis, untreated HIV, Liver cancer outside criteria
What proportion of patients added to the Liver transplant waiting list are transplanted within 1 year?
73%
How are liver transplants post DBD allocated?
Transplant benefit score
In which order is the liver usually plumbed in at transplant?
1) IVC
2) PV
3) HA
4) CBD
If used, when should sirolimus be started after liver transplant?
At least 3 months due to risk of hepatic artery thrombosis and impaired wound healing
When should steroids be avoided following liver transplant?
If for Hep C
What are the leading causes of death post liver transplant (after 1 year)
Malignancy (22%)
CVD (11%)
Infection (9%)
What is the rate of recurrence of PBC and PSC following liver transplant?
50% and 70% at 5 years
How does a urine leak post transplant present?
Perigraft collection
Rising creatitine
Falling urine output
How frequently should HLA status be reassessed in patients on the transplant list?
At least once every 3 months
If sensitising event then 2-4 weeks after this
Which subtype of Blood group A is least antigenic?
A2
What is the mortality at 5 years after elective liver transplant?
20%
What is the BANFF Classification?
Assessing for chronic rejection
Grade 1 - interstitial Inflammation with tubulitis (A/B)
A: Moderate tubulitis
B: Severe tubulitis
Grade 2 - Intimal arteritis
A: Mild/moderate
B: Severe
Grade 3 - Transmural arteritis
When is CD3/OKT mostly used?
In acute rejection where other measures have failed
(Muromonomab OKT)
Which class of antibodies mediate hyper acute rejection?
IgG
What agents might be useful for treatment of CMV infection?
Valganciclovir
Ganciclovir
Foscarnet
Cidofovir
How often should renal transplant criteria be reassessed if still on the list?
Annually
In patients with detectable HBV DNA, what antivirals are helpful pretransplant?
Entecavir and Tenofovir
Which immunosuppressant is specifically contraindicated in pregnancy?
Myocphenolate
Which immunosuppressant should be withdrawn when chronic rejection is suspected?
Tacrolimus
Which agent can be given to reduce the risk of non melanoma skin cancer in renal transplant patients?
Acitretin
Also favour sirolimus
At what GFR is retransplant offered?
10-15ml/min
Where does the most severe reperfusion injury occur?
At time of transplant
How does MMF work?
Inhibition of ionisine monophosphate dehydrogenase
How should fistula associated steal be treated?
Banding initially
What is often the mechanism of prolonged bleeding post fistula needling?
Venous outflow stenosis (ix fistulogram)
How should early problems with a pancreatic transplant be investigated?
Probably CT
What is the role of HLA matching in liver transplant?
It is not useful and not measured
how should bk virus detection be managed?
decrease immunosuppression
What are the Maastricht criteria?
1 to 5
3/4 controlled/suitable
How does Alemtuzumab work?
Anti-CD52
Campath
What diabetes complication is characteristically not reversed by transplant?
Peripheral neuropathy
What diabetes complication is characteristically not reversed by transplant?
Peripheral neuropathy
What is the incidence of wound complications in patients undergoing surgery on Sirolimus?
25-50% poor wound healing/seroma
how should a post transplant urine leak be managed?
decompress bladder
if no better –> surgery
if delayed consider nephrostomy
how should a post transplant urine leak be managed?
decompress bladder
if no better –> surgery
if delayed consider nephrostomy
what criteria indicate renal transplant?
-eGFR<15
-Or expected within 6 months and will convey survival benefit
When is the earliest a renal transplant biopsy might be performed?
5 days
How often is reoperation required for SPK?
25% bleeding!
what is a key factor differentiating renal vein from artery thrombosis?
Swelling of wound/kidney 3% vs 1%
What is the most common cause of late failure of AV fistulas?
Stenosis - reduction in vessel lumen by >50%
Neointimal proliferation –> angioplasty
How frequently are there accessory renal arteries?
30% L>R
How frequently are there accessory renal arteries?
30% L>R
What is the orientation of the renal hilum?
Vein Anteriorly then artery then ureter posteriorly
What is the 5 year survival of renal, liver and sb transplants?
80-90%
60-79%
<40%
What is the definitive treatment of choice for symptomatic lymphocoele post renal transplant?
Laparoscopic fenestration
Which immunosuppressant is associated with tremor?
Tacrolimus
What threshold should be used for vein diameter when making an AVF?
> 2cmm (patency at 3 months of 76% vs 16%)
What are the pros/cons of an elbow vs wrist fistula?
Pros - higher flow, easier to cannulate
Cons
– lower long term patency
– increased steal
– more arm swelling
– shorter vein for needling
What is the first line treatment for steal in an AVF?
Banding - praline suture around a balloon catheter to narrow venous outflow
then ?bypass (DRIL)
How does renal failure increase the risk of CVS disease?
-Volume overload due to excess fluid and anaemia –> LVH
-Arterial medial calcification (hyperparathyroidism)
-Cardiac myocyte injury due to uraemia, PTH and ATII
-Oxidant stress
-Hyperhomocysteinaemia
How should a patient with suspected chronic renal transplant rejection be investigated?
History of symptoms, compliance
Examination for fluid overload
Tests
- U&E, HbA1c, Tacrolimus levels
- Virology (CMV EBV, BK/JC)
- Urinalysis/culture
- USS kidney (RAS)
- Biopsy sometimes
When can calcineurin inhibitors be withdrawn?
> 12 months post transplant
No acute rejection in last 3 months
Biopsy demonstrating absence of cell/antibody mediating rejection
No contraindication to MMF
How can hepatic encephalopathy be classified?
World congress of gastroenterology classification system (minimal, episodic, persistent)
West Haven criteria
How is a fistula clinically assessed?
Palpable thrill (loss –> stenosis/thrombosis)
Aneurysmal dilatation
Redness/pain (infection)
Doppler flow rate (should be more than 300ml/min for AVF)
What are the Maastricht criteria?
I - DOA - uncontrolled
2 - Failed resuscitation - uncontrolled
3 - Awaiting Cardiac arrest - controlled
4 - Cardiac arrest in brainstem dead - controlled
5 - unexpected cardiac arrest in critically ill patient
When may organ donation be considered in patients awaiting cardiac death?
<30 mins of hypotension <50mmHg + SpO2<70% (Liver and Pancreas)
<4 hours of asystole (Kidneys)
5 minute standoff time, <15minutes to cold perfusion
What is the mechanism of anti-rejection of steroids?
Upregulate IL-10
Down regulate IL2, IL6 and IFN Gamma
What are the risk factors for primary non-function of a liver transplant?
–Donor
Increasing donor age
Steatosis
Elevated Sodium
DCD
–Recipient
Prolonged cold ischaemic and warm ischaemic time
haemodynamic instability
What are the biopsy characteristics of acute rejection (liver)?
Cellular (occurs in 20-80% at D5-30)
Portal inflammation
Bile duct inflammation
Venous inflammation
Banff criteria - indeterminate, mild, moderate, severe
Antibody
- Portal oedema
- ductular reaction
- neutrophil rich inflammatory infiltrate
When does Post Transplant Lymphoproliferative disease tend to present?
Most within 1 year, corresponding to aggressive immunosuppression.
Late presenters tend to have aggressive tumors and worse prognosis
What is PCKD?
AD multisystem, kidney, liver, spleen, pancreas, PKD1 gene 16p13.3, polycystic 1
Most frequent genetic cause of RF, 50% need RRT by 60
Presentation - Cyst haemorrhage, stones, infection, tumours. Hypertension common
Diagnosis - USS (Ravines Criteria)
Usually symptomatic treatment, but sometimes nephrectomy
How is PCLD treated?
Definitive –> transplant
Aspiration sclerotherapy if >5cm (ethanol)
Lap fenestration or resection
Sometimes octreotide, stop COCP
Why would you use a PTFE AVF?
Benefits
- Quick to mature
- Lower initial non-function rates
- Technically easier to manipulate
Use then native exhausted, ?leg-loop (SFA to CFV)
How is PD peritonitis managed?
- Treat exit site infections
- Use topical antibiotics to exit site
- Regular training
- Abx at insertion
- Diagnosis if cloudy effluent (culture like BC) + Abdominal pain or WCC >100/ul
—–Treat with intra-peritoneal abx unless septic, 14-28 days
—- consider removal if not improving by D5 or Pseudomonas
ISPD guidelines 2016
What is the relevance of HLA matching in pancreas transplant?
Small - reduced acute rejection and opportunistic infection, but similar graft survival
How are liver transplants matched?
ABO (although not mandatory)
Viral serology (CMV, Hepatitis)
Age, Liver size
NOT HLA
What are the common renal vascular anomalies?
Normal single renal artery 70%
Double renal artery 20% - accessory
Horseshoe Kidney
Retroaortic left renal vein
How should acute rejection be managed?
How are patients selected for SPK?
IDDM with ESRF
No significant CV disease
Age <60
What are the risks of PAK compared to SPK?
Patient older
Kidney different immunology to pancreas
Patient sensitised by kidney transplant
What are the indications for pancreas transplant alone (PTA)?
Life threatening diabetes complications
– Intractable hypoglycaemic unawareness
– Cardiac autonomic neuropathy
How is arterial reconstruction of a pancreatic transplant done?
Either with a cuff of aorta containing the coeliac axis or a donor iliac ‘y’ graft
(For SMA/Splenic artery)
How does acute pancreatic rejection manifest?
Rare alone if SPK - usually with kidney as well
Affects exocrine pancreas first (rise in temp/amylase)
Islet cell function only affected late
Non specific so may need biopsy if suspected
Usually reversible, treat with steroids and anti-T-cell
What are the complications of pancreatic transplant?
Vascular (Thrombosis 5%/haemorrhage - leaking of proteolytics)
Infective (systemic, local, fistulas)
Allograft pancreatitis (ischaemia-reperfusion or reflux)
80% 3 year survival after SPK
HLA matching independent
What influence does pancreas transplant have on diabetic complications?
–Stop/reverse nephropathy
–Risk of progression of non-proliferative retinopathy for 3 years post treatment
–Improvement of peripheral and autonomic neuropathy
–Improvement in microangiopathy
What are the contraindications to organ transplant broadly?
–Non-compliance/support network
–Predicted survival <5 years
–Predicted graft loss of >50% at 1 year
–Severe CVS comorbidity or anaesthetic contraindications
–Incurable malignancy
Organ specific
–Kidney – anti-GBM antibody disease
–Liver – ongoing substance abuse
