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THEME: Patient selection for transplantation
A Candidate in future following lifestyle changeB Further medical management before considerationC Further surgical management before considerationD High-priority candidateE Low-priority candidateF Standard priority candidateG Unsuitable candidate
For each of the clinical scenarios listed below, select the most likely patient classification. Each option may be used once, more than once, or not at all.
Scenario 1
You see a fit 50-year-old woman being assessed for renal transplantation. An ultrasound scan of her abdomen has revealed multiple gallstones. She has had the occasional bout of right upper quadrant pain but thought nothing of it. Liver function tests are normal.
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C Correct answer
Gallstones are a relative contraindication for renal transplantation. She requires a cholecystectomy before being put forward for a renal transplant.
Scenario 2
You see an 18-year-old girl on the high-dependency unit. She was admitted 3 days ago following a paracetamol overdose. She has severely deranged liver function tests and is developing renal impairment. Her Glasgow Coma Score (GCS) is 13/15. She was previously fit and well.
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D Correct answer
Paracetamol overdose can cause death by acute liver failure. The cause of early deaths is usually raised intracranial pressure. Later deaths can occur from multiorgan failure and systemic sepsis. If a patient survives the acute phase without a transplant, the liver will tend to recover without the development of cirrhosis.
Scenario 3
A 40-year-old type I diabetic with end-stage renal failure is seen in the renal transplant clinic. His body mass index (BMI) is 31 and he smokes 20 cigarettes a day.
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A Correct answer
Smoking and obesity are contraindications to renal transplantation.
Scenario 4
You see a 38-year-old woman in clinic following a full assessment for a liver transplant. She has end-stage liver disease secondary to primary biliary cirrhosis. She has been feeling very tired. On examination she looks jaundiced and has ascities for which she is taking diuretics. Blood tests reveal creatinine 220 mmol/l and international normalised ratio (INR) 2.4.
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D Correct answer
The three top causes of end-stage liver disease leading to liver transplantation in the UK are alcohol, hepatitis C and primary biliary sclerosis. It is often difficult to prioritise patients. In the USA they use the Model for End-Stage Liver Disease (MELD) scoring system. The MELD score is based on three biochemical variables, serum bilirubin, serum creatinine and international normalised ratio (INR). Retrospective and prospective studies have shown it to be highly predictive of 3-month mortality in patients with chronic liver disease. The higher the MELD score, the higher priority the patient.
THEME: Conditions leading to kidney transplantation
A Chronic glomerulonephritisB Diabetes mellitusC Hypertensive nephrosclerosisD Chronic interstitial nephritisE Polycystic kidney diseaseF Systemic lupus erthematousus
For each of the clinical scenarios listed below, select the most likely diagnosis. Each option may be used once, more than once, or not at all.
Scenario 1
A 51-year-old Asian woman is seen in clinic. She is complaining of feeling tired and passing foamy urine. On examination she has ankle swelling. Her urine is positive for glucose and protein.
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B Correct answer
Diabetic nephropathy is the leading cause of chronic renal failure in Western societies. It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes. Diabetes is responsible for 30–40% of all end-stage renal disease.
Scenario 2
A 50-year-old woman is seen in the renal clinic. She has been referred because of a raised creatinine and mild proteinuria. She has been taking long-term non-steroidal anti-inflammatory drugs for low back pain.
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D Correct answer
Analgesic nephropathy is the most common cause of chronic interstitial nephritis worldwide. It has an insidious nature and is often diagnosed incidentally on routine blood tests or evaluation of hypertension. Patients are usually asymptomatic. Clinical investigations may show modest elevation in serum creatinine and evidence of renal tubular acidosis. Proteinuria is usually mild (<1 g/dl).
Scenario 3
You see a 48-year-old man on the ward who is awaiting a renal transplantation. He is receiving haemodialysis. He is anaemic and is being treated for hypertension. He has proteinuria of >1g/day. His renal biopsy showed his renal tubules were disrupted and atrophic with marked interstitial fibrosis and arterial and arteriolar sclerosis.
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A Correct answer
Chronic glomerulonephritis is characterised by irreversible and progressive glomerular and tubulointerstitial fibrosis, ultimately leading to a reduction in the glomerular filtration rate (GFR) and retention of toxins.
Scenario 4
You see a 55-year-old man with end-stage renal failure. He says his father also had problems with his kidneys. On examination he has bilateral blottable masses in his flanks.
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E Correct answer
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans. It is the most frequent genetic cause of renal failure in adults.
THEME: Types of tissue transplantation
A AutograftB AllograftC MonograftD IsograftE Xenograft
For each of the clinical scenarios listed below, select the most appropriate description of the transplanted tissue. Each option may be used once, more than once, or not at all.
Scenario 1
A patient receives a porcine aortic valve replacement.
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E Correct answer
A xenograft (or heterograft) is an organ or tissue transferred from one species to another species.
Scenario 2
A 25-year-old woman with end-stage renal failure receives a kidney for transplantation from her twin sister.
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D Correct answer
An isograft is an organ or tissue obtained from a donor genetically identical to the recipient.
Scenario 3
A woman undergoes renal transplantation. The kidney had been harvested from a patient with confirmed brainstem death.
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B Correct answer
An allograft (or homograft) is an organ or tissue transplanted from a donor of the same species but different genetic make-up.
Scenario 4
A 16 year-old boy suffers burns to his chest. A partial-thickness skin graft is harvested from his thigh and used to cover part of his chest.
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A Correct answer
An autograft is tissue taken from one site and grafted to another site on the same person.
THEME: Drug therapies related to transplantation
A Antithymocyte globulin (ATG)B AzothioprineC CiclosporinD Methotrexate
E Macrolide antibioticF MycophenolateG Prednisolone
For each of the descriptions listed below, select the correct drug name. Each option may be used once, more than once, or not at all.
Scenario 1
Antimetabolite which interferes with DNA synthesis, repair, and cellular replication. A short course can be administered for prophylaxis of acute graft versus host disease.
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D Correct answer
Scenario 2
A calcineurin inhibitor that diminishes interleukin-2 (IL-2) production in activated T cells.
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C Correct answer
Scenario 3
Immunosuppressant used to treat autoimmune disorders. It decreases inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leucocyte activity.
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G Correct answer
Scenario 4
Inhibits purine synthesis and so lymphocyte proliferation. It is used as an induction agent for prophylaxis of organ rejection.
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F Correct answer
THEME: Consent for organ donation
A Discuss organ donation with relativesB Seek consent from the coronerC Respect relatives wishes, unable to go ahead with organ harvestD Invalid consent, unable to go ahead with organ harvestE Not suitable for organ donationF Valid consent, proceed with organ harvest
For each of the clinical scenarios listed below, select the most likely course of action. Each option may be used once, more than once, or not at all.
Scenario 1
A 25-year-old man is on the intensive therapy unit (ITU) following a severe head injury. He has been confirmed brainstem dead. He is a suitable candidate for organ donation but is not on the organ donation register (ODR). His relatives say he never expressed a wish to donate his organs. They themselves do not object and agree with donation.
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F Correct answer
Although the man never expressed a view and is not on the register his relatives do not object. This ‘lack of objection’ is sufficient consent.
Scenario 2
Brainstem death is confirmed in a 34-year-old woman on ITU. She is on the organ donation register. You discuss this with her relatives and they object to organ donation.
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F Correct answer
The patient had expressed a wish to donate his organs by registering with the organ donation register (ODR). There is no evidence that the patient changed his mind before death. Her relatives holding an opposing view does not invalidate the consent. Time should be spent with the relatives fully informing them about organ donation and address any issues they have.
Scenario 3
A 46-year-old man is on ITU following a road traffic collision. He has been confirmed brainstem dead. He is a suitable candidate for organ donation but is not on the register. He does not have any close relatives. A friend is not sure what his wishes would have been.
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B Correct answer
The Human Tissue Act (1961) states that only the person lawfully in possession of the body or his/her designated other can authorise the removal of organs or tissues from the body. It states:
“The person lawfully in possession of the body has powers and duties in connection with removal of organs. The person authorises the removal of any part from the body for the said purposes (therapeutic or medical education, or research) if having made such reasonable enquiry as may be practicable, he has no reason to believe: (a) that the deceased had expressed an objection to his body being so dealt with after his death, and had not withdrawn it; or (b) that the surviving spouse or any surviving relative of the deceased objects to the body being so dealt with.”
Where a deceased person is in an NHS hospital or organisation, the person with control and management of the hospital (usually the chief executive/medical director) is the person lawfully in possession of the body until such time as it is claimed by the person who has right to possession for the purpose of disposal (usually the executor or next of kin of the patient) or, by reason of their statutory obligations, the coroner or procurator fiscal (Department of Health Working Party – Code of Practice for the Diagnosis of Brain Stem Death 1998).
In situations where the cause of death was sudden, not due to natural causes or unexpected and/or the doctor has not treated the deceased during his/her last illness, the coroner/procurator fiscal must be informed (Coroner’s Act 1988). The medical staff involved in the care of the patient should contact the coroner/procurator fiscal to obtain authorisation for organ/tissue donation or the donor transplant co-ordinator/tissue co-ordinator may do this on behalf of the medical staff.
Scenario 4
A 50-year-old woman on ITU is confirmed brainstem dead. She is on the ODR and her relatives have already expressed a wish that her organs are harvested. According to her relatives she is fit and well. In the past she has been ‘cured’ following treatment for early breast cancer.
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E Correct answer
The patient has previously had a cancer. This is a contraindication for organ donation.
THEME: Mean graft survival rates at one year following transplantation
A > 90%B 90%C 80%D 70%E 60%F 50%G 40%
For each of the clinical scenarios listed below, select the closest survival rate. Each option may be used once, more than once, or not at all.
Scenario 1
A 20-year-old man had a living donor renal allograft transplant.
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A Correct answer
Living donor grafts have a slightly better survival rate than cadaveric grafts.
Scenario 2
A 30-year-old woman has an uncomplicated liver transplant for primary biliary cirrhosis.
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C Correct answer
This can vary with patient factors and indications for transplant.
Scenario 3
A 22-year-old man undergoes a lung transplant for cystic fibrosis.
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D Correct answer
The International Society for Heart and Lung Transplantation report 1-year survival rates of 71%, and 5-year survival rates of 45% following lung transplantation.
Scenario 4
A 40-year-old woman with type 1 diabetes mellitus has a pancreas transplant.
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E Correct answer
Pancreatic graft survival continues to improve. Graft survival is highest when the pancreas is transplanted in combination with a renal allograft.
THEME: Transplant rejection
A Accelerated rejectionB Acute rejectionC Chronic rejectionD Hyperacute rejectionE Not undergoing rejectionF Severe acute rejection
For each of the clinical scenarios listed below, select the most likely answer. Each option may be used once, more than once, or not at all.
Scenario 1
You are assisting with a renal allograft transplantation. Once perfusion of the kidney is established it becomes grossly mottled and cyanotic. The capsule begins to bulge.
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D Correct answer
The kidney is undergoing antibody mediated hyperacute rejection. This generally occurs within 24 h of the operation. In severe cases it can occur following perfusion of the allograft. It is an irreversible process and the patient will have to restart dialysis.
Scenario 2
You review a 45-year-old woman on the ward round. She had a renal transplantation 5 days ago. She is complaining of some discomfort in the region of the transplant. Her renal function had been improving but has now deteriorated over the last two days.
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A Correct answer
Accelerated rejection develops up to a week after transplantation. It is generally due to cell-mediated immune injury. Both delayed hypersensitivity and cytotoxicity mechanisms are likely to be involved. It is usually irreversible.
Scenario 3
You receive the histopathology report for a patient who you suspect is rejecting the kidney transplant received 90 days ago. The findings are of, ‘transmural arteritis and transmural fibrinoid change with necrosis of smooth muscle cells’.
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F Correct answer
Acute rejection occurs between a week and 100 days following transplantation. The severity of rejection can be assessed by taking a needle biopsy of the allograft. Acute rejection is recognised by the presence of tubulitis and intimal arteritis. The Banff System can be used to classify acute rejection into mild, moderate, and severe. The category depends on the intensity of the infiltrate, and the severity of tubulitis and
intimal arteritis. In this case there was also necrosis of muscle cells which means it is grade 3 and therefore severe acute rejection.
Scenario 4
You review a 50-year-old man in clinic. He had a renal transplantation 200 days ago. He feels tired but otherwise well. His renal function is deteriorating and he has developed proteinuria.
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C Correct answer
This gentleman has chronic allograft nephropathy. It is characterised by slowly progressive graft dysfunction which leads to chronic renal failure. In addition, many patients develop nephrotic-range proteinuria.
Histopathological examination of a renal allograft biopsy may show varying combinations of lesions. These include: chronic transplant glomerulopathy, ischaemic glomerulopathy, interstitial fibrosis, tubular atrophy, arteriosclerosis and arteriolar hyalinosis.
THEME: Complications following liver transplantation
A Primary graft failureB Biliary obstructionC Chronic graft rejectionD Hepatic artery thrombosisE HepatitisF Normal postoperative courseG Post-transplant lymphoproliferative disorder
For each of the clinical scenarios listed below, select the most likely diagnosis. Each option may be used once, more than once, or not at all.
Scenario 1
At the 6-month review following a liver transplant a patient says they feel unwell. They have been feeling tired, have a sore throat and night sweats. According to your notes they have also lost weight.
G Correct answer
Post-transplant lymphoproliferative disorders (PTLDs) may develop at any time after transplantation. They are usually associated with Epstein–Barr virus infection and are a consequence of the high level of immunosuppression achieved with current regimens. The usual management is to reduce the immunosuppression and treatment with acyclovir.
Scenario 2
5 days post-transplant a patient develops a high temperature and their liver function tests have deteriorated. Blood cultures are positive for Escherichia coli.
D Correct answer
A high temperature, deranged liver function tests and positive blood cultures in the postoperative period following liver transplantation is virtually pathognomic of hepatic artery thrombosis. Doppler ultrasound is used to assess hepatic artery patency. Arteriography can be used if Doppler fails to visualise the artery. Patients presenting in the early postoperative period usually require re-transplantation.
Scenario 3
2 days post-transplant a patient deteriorates and has a seizure. Blood tests show grossly deranged liver function tests and confirm a suspected coagulopathy.
A Correct answer
Approximately 7% of grafts undergo primary failure. It is a very serious complication with a poor prognosis. Urgent re-transplantation is required.
THEME: Drug therapy for suspected transplant rejection
A Antithymocyte globulin (ATG)B AzothioprineC CiclosporinD MethotrexateE MycophenolateF Methylprednisolone
For each of the clinical scenarios listed below, select the most
appropriate first-line drug therapy. Each option may be used once, more than once, or not at all.
Scenario 1
You receive a histopathology report for a patient who you suspect is rejecting the renal allograft they received 90 days ago. The findings are of ‘transmural arteritis and transmural fibrinoid change with necrosis of smooth muscle cells’.
F Correct answer
First-line therapy in acute rejection is high-dose steroids in addition to the original immunoprophylaxis.
Scenario 2
You review a 45-year-old woman on the ward round. She had a renal transplantation one week ago. She is now complaining of discomfort in the region of the transplant. Her renal function had been improving but has deteriorated over the last two days.
F Correct answer
First-line therapy in acute rejection is high-dose steroids in addition to the original immunoprophylaxis.
Scenario 3
A patient with established acute graft versus host rejection is 30 days following renal transplantation. They have been receiving first line therapy for 7 days but there has been no change in their condition
A Correct answer
Failure of first-line therapy is defined as progression of acute graft versus host disease after 3 days, no change after 7 days, or incomplete response after 14 days of methylprednisolone. Secondary therapy includes ATG and monoclonal antibody therapy.
THEME: Renal transplant
A Acute rejection B Blood group mismatch C Chronic rejectionD Hyperacute rejection
Match the following concerning transplantation. Each option may be used once, more than once, or not at all.
Hyperacute rejection occurs immediately, as a result of a reaction from pre-existing antibodies to the transplanted tissue, eg ABO blood type mismatch. Acute rejection occurs as a result of HLA type mismatch, and is controlled by matching donor and recipient HLA types and with immunosuppressive drugs. The humoral immune system is responsible for chronic rejection, which can take months or years to occur.
Scenario 1
The humoral system is responsible for this.
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C Correct answer
C – Chronic rejection
Scenario 2
Cellular immunity is responsible for this.
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A Correct answer
A – Acute rejection
Scenario 3
This causes haemolysis.
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B Correct answer
B – Blood group mismatch
Scenario 4
Pre-sensitisation is responsible for this.
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D Correct answer
D – Hyperacute rejection
THEME: Complications following kidney transplantation
A Acute graft rejectionB Chronic graft rejectionC Delayed graft functionD LymphoceleE Renal artery stenosisF Ureteric obstruction
For each of the clinical scenarios listed below, select the most likely complication. Each option may be used once, more than once, or not at all.
Scenario 1
6 months following transplantation a patient is seen in clinic with a mild swelling and tenderness in the region of the transplant. Their renal function has deteriorated. A computed tomography (CT) scan demonstrates a collection between the lower pole of the kidney and bladder.
A
D Correct answer
Leakage from perivascular lymphatic vessels can lead to significant collections of lymph between the lower pole of the transplanted kidney and the bladder. A lymphocele can present as pain, swelling and impaired renal function within the first year following transplantation. Treatment is by drainage. Percutaneous drainage has a high infection risk and is rarely successful, due to a high recurrence rate. Laparoscopic drainage of the collection in to the abdominal cavity is the treatment of choice.
Scenario 2
You are referred a patient by their general practitioner (GP). They underwent a renal transplantation 3 years ago. The patient has been complaining of headaches and dizzy spells. The GP reports an abrupt onset of unexplained hypertension.
A
E Correct answer
Renal artery stenosis complicates 2–10% of renal transplants. It may be confirmed on Doppler ultrasound. It can be managed using percutaneous angioplasty and stent placement.
Scenario 3
You review a 50-year-old man in clinic. He had a renal transplantation 200 days ago. He feels tired but otherwise well. His renal function is deteriorating and he has developed proteinuria.
A
B Correct answer
This gentleman has chronic allograft nephropathy. It is characterised by slowly progressive graft dysfunction which leads to chronic renal failure. In addition many patients develop nephrotic-range proteinuria. Histopathological examination of a renal allograft biopsy may show varying combinations of lesions. These include: chronic transplant glomerulopathy, ischaemic glomerulopathy, interstitial fibrosis, tubular atrophy, arteriosclerosis and arteriolar hyalinosis.
THEME: Complications of cadaveric organ transplantation
A Acute rejection B Arterial thrombosis
C Azathioprine side-effects D Chronic rejection E Cyclosporin side-effects F Cytomegalovirus infection G Graft-versus-host diseaseH Hyperacute rejectionI MalignancyJ Primary graft non-functionK Steroid side-effectsL Venous thrombosis
The following patients have all previously undergone cadaveric organ transplantation. From the above list, select the most likely complication. The items may be used once, more than once, or not at all.
Scenario 1
A 25-year-old woman with cystic fibrosis underwent a heart and lung transplant 4 months ago, and is currently receiving triple immunotherapy. She attends the follow-up clinic for a routine check-up. She reports sore gums and excessive facial hair. On examination she is hypertensive. Urea & electrolyte results are as follows: Na+ 139 mmol/litre, K+ 5.7 mmol/litre, urea 9.9 mmol/litre, creatinine 140 µmol/litre.
A
E Correct answer
E – Cyclosporin side-effects
Cyclosporin A is an example of a calcineurin inhibitor. Cyclosporin-based triple immunosuppression with corticosteroids and azathioprine remains the most popular regimen in the UK. It is used prophylactically and therapeutically to address rejection following organ transplantation. Sideeffects of cyclosporin include nephrotoxicity, hypertension, hirsutism, tremor, gingival hyperplasia and hepatotoxicity. Long-term use increases the risk of development of malignancy (5% of patients), most commonly basal or squamous cell carcinomas.
Scenario 2
A 58-year-old man had a liver transplant 7 weeks ago. He attends The Emergency Department with a 24-h history of malaise, fever and myalgia and respiratory distress
going upstairs. He is currently receiving triple immunosuppression. On examination, he is unwell and dyspnoeic at rest. He has a pulse rate of 105/min, blood pressure is 95/60 mmHg, temperature is 38.3°C and respiratory rate is 28 breaths/min. Oxygen saturation is 90% on air.
A
F Correct answer
F – Cytomegalovirus infection
In addition to the development of malignancy, immunosuppression increases the risk of infection. Cytomegalovirus (CMV) is a member of the herpes group of viruses. Primary infection in a seronegative individual who receives a graft from a seropositive donor typically occurs 6 weeks posttransplantation, and results in the most severe disease. The main symptoms of CMV infection are usually non-specific and include fever, night sweats, fatigue and myalgia. Retinitis is pathognomonic, but rarely seen in the transplant population. Respiratory distress, noticed at first during exercise, may give a clue to early CMV pneumonitis. Patients may also present with CMV encephalitis or gastrointestinal infection, characterised by dysphagia, diarrhoea, nausea and abdominal pain. Reactivation of latent CMV infection may also occur in immunosuppressed patients, although the infection is usually less severe.
Scenario 3
A 41-year-old woman underwent renal transplantation 18 months ago. She attends follow-up clinic and is currently asymptomatic. On examination her blood pressure is 150/110 and urinalysis reveals 3+ protein. Urine culture is negative. A renal ultrasound scan reveals a normal collecting system. Renal biopsy demonstrates intrarenal arteriosclerosis with associated glomerular atrophy and interstitial fibrosis.
A
D Correct answer
D – Chronic rejection
Chronic rejection is characterised clinically by a progressive deterioration in graft function occurring months to years after transplantation and is associated with typical histological changes of graft atherosclerosis and fibrosis. By contrast, acute rejection occurs within the first 3 months after transplantation, and hyperacute rejection occurs within hours. For the diagnosis of chronic rejection to be made, other causes of graft dysfunction must be excluded (eg infection, calcineurin antagonist toxicity, etc), and a transplant graft biopsy is required to confirm the diagnosis histologically. For renal transplantation, graft dysfunction is manifested by a rise in serum creatinine as a result of progressive decline in the glomerular filtration rate. There is associated
proteinuria and worsening hypertension, with the diastolic component classically rising in advance of the systolic component
