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Question 1-3 of 20
Theme: Transplantation
A.
B.
C.
D.

Xenograft
Allograft
Autograft
Isograft

Please select the type of transplantation that has occurred in the situation described. Each option may be used
once, more than once or not at all.

1.

A 38 year old lady donates her kidney to her identical twin sibling.
Isograft
Theme from January 2013
Identical twin- twin donations are usually genetically identical and are therefore isografts.

2.

A 53 year old man with severe angina undergoes a coronary artery bypass procedure and his long
saphenous vein is used as a bypass conduit.
Autograft
The long saphenous vein is one of the commonest autografts in surgery.

3.

A 38 year old lady donates her kidney to her niece.

Allograft
Though related this donor will not be genetically identical and thus this will be an allograft.

Transplant types

Graft
Allograft

Features
Transplant of tissue from genetically non identical donor from
the same species
Isograft
Graft of tissue between two individuals who are genetically
identical
Autograft Transplantation of organs or tissues from one part of the body to
another in the same individual
Xenograft Tissue transplanted from another species

Uses
Solid organ transplant from non
related donor
Solid organ transplant in
identical twins
Skin graft
Porcine heart valve

Question 4 of 20
A 43 year old lady undergoes a live donor related renal transplant. Over the next few years it is noted that her
renal function progressively deteriorates. What is the most likely underlying explanation?
A. Type I hypersensitivity reaction
B. Type III hypersensitivity reaction
C. Type II hypersensitivity reaction
D. Type IV hypersensitivity reaction
E. None of the above
Chronic rejection of renal transplants is mediated via T lymphocytes and is therefore a type IV hypersensitivity
reaction. This process can be mitigated by immunosupression.
Organ Transplant
A number of different organ and tissue transplants are now available. In many cases an allograft is performed,
where an organ is transplanted from one individual to another. Allografts will elicit an immune response and
this is one of the main reasons for organ rejection.
Graft rejection occurs because allografts have allelic differences at genes that code immunohistocompatability
complex genes. The main antigens that give rise to rejection are:

ABO blood group

Human leucocyte antigens (HLA)
Minor histocompatability antigens

ABO Matching
ABO incompatibility will result in early organ rejection (hyperacute) because of pre existing antibodies to other
groups. Group O donors can give organs to any type of ABO recipient whereas group AB donor can only
donate to AB recipient.
HLA System
The four most important HLA alleles are:

HLA A
HLA B
HLA C
HLA DR

An ideal organ match would be one in which all 8 alleles are matched (remember 2 from each parent, four each
= 8 alleles). Modern immunosuppressive regimes help to manage the potential rejection due to HLA
mismatching. However, the greater the number of mismatches the worse the long term outcome will be. T
lymphocytes will recognise antigens bound to HLA molecules and then will then become activated. Clonal
expansion then occurs with a response directed against that antigen.

Types of organ rejection

Hyperacute. This occurs immediately through presence of pre formed antigens (such as ABO
incompatibility).
Acute. Occurs during the first 6 months and is usually T cell mediated. Usually tissue infiltrates and
vascular lesions.
Chronic. Occurs after the first 6 months. Vascular changes predominate.

Hyperacute
Renal transplants at greatest risk and liver transplants at least risk. Although ABO incompatibility and HLA
Class I incompatible transplants will all fare worse in long term.
Acute
All organs may undergo acute rejection. Mononuclear cell infiltrates predominate. All types of transplanted
organ are susceptible and it may occur in up to 50% cases.
Chronic
Again all transplants with HLA mismatch may suffer this fate. Previous acute rejections and other
immunosensitising events all increase the risk. Vascular changes are most prominent with myointimal
proliferation leading to organ ischaemia. Organ specific changes are also seen such as loss of acinar cells in
pancreas transplants and rapidly progressive coronary artery disease in cardiac transplants.

Surgical overview-Renal transplantation

A brief overview of the steps involved in renal transplantation is given.
Patients with end stage renal failure who are dialysis dependent or likely to become so in the immediate future
are considered for transplant. Exclusion criteria include; active malignancy, old age (due to limited organ
availability). Patients are medically optimised.
Donor kidneys, these may be taken from live related donors and close family, members may have less HLA
mismatch than members of the general population. Laparoscopic donor nephrectomy further minimises the
operative morbidity for the donor. Other organs are typically taken from brain dead or dying patients who have
a cardiac arrest and in whom resuscitation is futile. The key event is to minimise the warm ischaemic time in the
donor phase.
The kidney once removed is usually prepared on the bench in theatre by the transplant surgeon immediately
prior to implantation and factors such as accessory renal arteries and vessel length are assessed and managed.
For first time recipients the operation is performed under general anaesthesia. A Rutherford-Morrison incision
is made on the preferred side. This provides excellent extraperitoneal access to the iliac vessels. The external
iliac artery and vein are dissected out and following systemic heparinisation are cross clamped. The vein and
artery are anastamosed to the iliacs and the clamps removed. The ureter is then implanted into the bladder and a
stent is usually placed to maintain patency. The wounds are then closed and the patient recovered from surgery.
In the immediate phase a common problem encountered in cadaveric kidneys is acute tubular necrosis and this
tends to resolve.
Graft survival times from cadaveric donors are typically of the order of 9 years and monozygotic twin transplant
(live donor) may survive as long as 25 years.

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Question 5-7 of 20
Theme: Renal transplant complications
A.
B.
C.
D.
E.
F.
G.

Acute tubular necrosis

Renal artery thrombosis
Bladder occlusion
Ureteric occlusion
Acute rejection
Acute on chronic rejection
Hyperacute rejection

For each of the scenarios given please select the most likely underlying process from the list below. Each option
may be used once, more than once or not at all.

5.

A 45 year old man with end stage renal failure undergoes a cadaveric renal transplant. The transplanted
organ has a cold ischaemic time of 26 hours and a warm ischaemic time of 54 minutes. Post
operatively the patient receives immunosuppressive therapy. Ten days later the patient has gained
weight, becomes oliguric and feels systemically unwell. He also complains of swelling over the
transplant site that is painful.
Acute rejection
Theme from April 2012 Exam
The features described are those of worsening graft function and acute rejection. The fact that there is a
10 day delay goes against hyperacute rejection. Cold ischaemic times are a major factor for delayed
graft function. However, even 26 hours is not incompatible with graft survival.

6.

A 44 year old man with end stage renal failure undergoes a live donor renal transplant. During the
immediate post operative period a good urine output is recorded. However, on return to the ward the
nursing staff notice that the urinary catheter is no longer draining. However, the urostomy is
continuing to drain urine.
You answered Ureteric occlusion
The correct answer is Bladder occlusion
The most likely explanation for this event is a blocked catheter. This may be the result of blood clot
from the ureteric anastomosis. Bladder irrigation will usually resolve the problem.

7.

A 43 year old man undergoes a live donor renal transplant. The donor's right kidney is anastomosed to
the recipient. On removal of the arterial clamps there is good urinary flow noted and the wounds are
closed. On return to the ward the nurses notice that the patient suddenly becomes anuric and irrigation
of the bladder does not improve the situation.
You answered Acute tubular necrosis

The correct answer is Renal artery thrombosis

Right sided live donor transplants are extremely rare. This is because the vena cava precludes
mobilisation of the right renal artery. The short right renal artery that is produced therefore presents a
major challenge. The sudden cessation of urine output in this context is highly suggestive of an acute
thrombosis. Delay in thrombectomy beyond 1 hour almost inevitably results in graft loss.

Complications following renal transplant

Renal transplantation is widely practised. The commonest technical related complications are related to the
ureteric anastomosis. The warm ischaemic time is also of considerable importance and graft survival is directly
related to this. Long warm ischaemic times increase the risk of acute tubular necrosis which may occur in all
types of renal transplanation and provided other insults are minimised, will usually recover. Organ rejection
may occur at any phase following the transplantation process.
Immunological complications
Types of organ rejection

Hyperacute. This occurs immediately through presence of pre formed antibody (such as ABO
incompatibility).
Acute. Occurs during the first 6 months and is usually T cell mediated. Usually tissue infiltrates and
vascular lesions.
Chronic. Occurs after the first 6 months. Vascular changes predominate.

Hyperacute
Renal transplants are most susceptible to this process. Risk factors include major HLA mismatch and ABO
incompatibility. The rejection occurs almost immediately and the macroscopic features may become manifest
following completion of the vascular anastomosis and removal of clamps. The kidney becomes mottled, dusky
and the vessels will thrombose. The only treatment is removal of the graft, if left in situ it will result in abscess
formation.
Acute
All organs may undergo acute rejection. Mononuclear cell infiltrates predominate. All types of transplanted
organ are susceptible and it may occur in up to 50% cases. Most cases can be managed medically.
Chronic
Again all transplants with HLA mismatch may suffer this fate. Previous acute rejections and other
immunosensitising events all increase the risk. Vascular changes are most prominent with myointimal
proliferation leading to organ ischaemia. Organ specific changes are also seen such as loss of acinar cells in
pancreas transplants and rapidly progressive coronary artery disease in cardiac transplants.
Technical complications
Complication
Presenting features
Renal artery
Sudden complete loss of urine output
thrombosis

Treatment
Immediate surgery may salvage the graft, delays
beyond 30 minutes are associated with a high rate
of graft loss

Renal artery
stenosis
Renal vein
thrombosis
Urine leaks

Lymphocele

Uncontrolled hypertension, allograft

dysfunction and oedema
Pain and swelling over the graft site,
haematuria and oliguria
Diminished urine output, rising
creatinine, fever and abdominal pain

Angioplasty is the treatment of choice

The graft is usually lost

USS shows perigraft collection, necrosis of ureter

tip is the commonest cause and the anastomosis
may need revision
Common complication (occurs in 15%), May be drained with percutaneous technique and
may present as a mass, if large may
sclerotherapy, or intraperitoneal drainage
compress ureter

Question 8 of 20
A 43 year old man undergoes a cadaveric renal transplant. The operation is uncomplicated. On removal of the
vascular clamps the transplanted kidney immediately turns dusky and over the ensuing hours appears non
viable. Which of the following best explains this event?
A. Chronic rejection
B. Hyper acute rejection
C. Acute rejection
D. Sub chronic rejection
E. Infection of the graft
Immediate rejection is due to the presence of pre-existing antibodies e.g. ABO mismatch. The transplanted
organ should be removed.
Organ Transplant
A number of different organ and tissue transplants are now available. In many cases an allograft is performed,
where an organ is transplanted from one individual to another. Allografts will elicit an immune response and
this is one of the main reasons for organ rejection.
Graft rejection occurs because allografts have allelic differences at genes that code immunohistocompatability
complex genes. The main antigens that give rise to rejection are:

ABO blood group

Human leucocyte antigens (HLA)
Minor histocompatability antigens

ABO Matching
ABO incompatibility will result in early organ rejection (hyperacute) because of pre existing antibodies to other
groups. Group O donors can give organs to any type of ABO recipient whereas group AB donor can only
donate to AB recipient.

HLA System
The four most important HLA alleles are:

HLA A
HLA B
HLA C
HLA DR

An ideal organ match would be one in which all 8 alleles are matched (remember 2 from each parent, four each
= 8 alleles). Modern immunosuppressive regimes help to manage the potential rejection due to HLA
mismatching. However, the greater the number of mismatches the worse the long term outcome will be. T
lymphocytes will recognise antigens bound to HLA molecules and then will then become activated. Clonal
expansion then occurs with a response directed against that antigen.
Types of organ rejection

Hyperacute. This occurs immediately through presence of pre formed antigens (such as ABO
incompatibility).
Acute. Occurs during the first 6 months and is usually T cell mediated. Usually tissue infiltrates and
vascular lesions.
Chronic. Occurs after the first 6 months. Vascular changes predominate.

Hyperacute
Renal transplants at greatest risk and liver transplants at least risk. Although ABO incompatibility and HLA
Class I incompatible transplants will all fare worse in long term.
Acute
All organs may undergo acute rejection. Mononuclear cell infiltrates predominate. All types of transplanted
organ are susceptible and it may occur in up to 50% cases.
Chronic
Again all transplants with HLA mismatch may suffer this fate. Previous acute rejections and other
immunosensitising events all increase the risk. Vascular changes are most prominent with myointimal
proliferation leading to organ ischaemia. Organ specific changes are also seen such as loss of acinar cells in
pancreas transplants and rapidly progressive coronary artery disease in cardiac transplants.

Surgical overview-Renal transplantation

A brief overview of the steps involved in renal transplantation is given.
Patients with end stage renal failure who are dialysis dependent or likely to become so in the immediate future
are considered for transplant. Exclusion criteria include; active malignancy, old age (due to limited organ
availability). Patients are medically optimised.
Donor kidneys, these may be taken from live related donors and close family, members may have less HLA
mismatch than members of the general population. Laparoscopic donor nephrectomy further minimises the
operative morbidity for the donor. Other organs are typically taken from brain dead or dying patients who have
a cardiac arrest and in whom resuscitation is futile. The key event is to minimise the warm ischaemic time in the
donor phase.
The kidney once removed is usually prepared on the bench in theatre by the transplant surgeon immediately

prior to implantation and factors such as accessory renal arteries and vessel length are assessed and managed.
For first time recipients the operation is performed under general anaesthesia. A Rutherford-Morrison incision
is made on the preferred side. This provides excellent extraperitoneal access to the iliac vessels. The external
iliac artery and vein are dissected out and following systemic heparinisation are cross clamped. The vein and
artery are anastamosed to the iliacs and the clamps removed. The ureter is then implanted into the bladder and a
stent is usually placed to maintain patency. The wounds are then closed and the patient recovered from surgery.
In the immediate phase a common problem encountered in cadaveric kidneys is acute tubular necrosis and this
tends to resolve.
Graft survival times from cadaveric donors are typically of the order of 9 years and monozygotic twin transplant
(live donor) may survive as long as 25 years.

Question 9 of 20
A 48 year old lady with end stage renal failure receives a cadaveric renal transplant. The organ is ABO group
matched only. On completion of the vascular anastomoses the surgeons remove the clamps. Over the course of
the next twelve minutes the donated kidney becomes dusky and swollen and appears non viable. Which of the
following is the most likely process that has caused this event?
A. IgG anti HLA Class I antibodies in the recipient
B. IgM anti HLA Class I antibodies in the recipient
C. IgG anti HLA Class I antibodies from the donor
D. IgM anti HLA Class I antibodies from the donor
E. IgM anti HLA Class II antibodies from the recipient
Episodes of hyperacute rejection are typically due to preformed antibodies. ABO mismatch is the best example.
However, IgG anti HLA Class I antibodies are another potential cause. These events are now seen less
commonly because the cross matching process generally takes this possibility into account.

Question 10 of 20
A 54-year-old man who has end stage diabetic nephropathy is being assessed for a renal transplant. When
assessing the HLA matching between donor and recipient what is the most important HLA antigen to match?
A. DP
B. B
C. DR
D. C

E. A
Renal transplant HLA matching - DR is the
most important

Renal transplant:HLA typing and graft failure

The human leucocyte antigen (HLA) system is the name given to the major histocompatibility complex (MHC)
in humans. It is coded for on chromosome 6.
Some basic points on the HLA system

Class 1 antigens include A, B and C. Class 2 antigens include DP,DQ and DR

When HLA matching for a renal transplant the relative importance of the HLA antigens are as follows
DR > B > A

Graft survival

1 year = 90%, 10 years = 60% for cadaveric transplants

1 year = 95%, 10 years = 70% for living-donor transplants

Post-op problems

ATN of graft
Vascular thrombosis
Urine leakage
UTI

Hyperacute acute rejection

Due to antibodies against donor HLA type 1 antigens

Rarely seen due to HLA matching

Acute graft failure (< 6 months)

Usually due to mismatched HLA

Other causes include cytomegalovirus infection
Management: give steroids, if resistant use monoclonal antibodies

Causes of chronic graft failure (> 6 months)

Chronic allograft nephropathy

Ureteric obstruction
Recurrence of original renal disease (MCGN > IgA > FSGS)

Question 11 of 20
A 49 year old female is due to undergo a renal transplant. Apart from ABO compatibility which of the
following is most important in matching donor and recipient organs?
A. HLA-DR
B. Rhesus
C. HLA- A
D. HLA-B
E. Kidd
Theme from January 2013 Exam
The effect of HLA-DR mismatches are the most clinically significant, since HLA-DR mismatch increases graft
loss five fold. HLA-B increases graft loss three fold and HLA-A increases the risk two fold. Rhesus is not used
to match organs to recipients. Kidd is a minor group and of no significance.

Question 12 of 20
Which of the following transplants is most susceptible to donor- recipient HLA mismatches?
A. Skin
B. Renal
C. Liver
D. Corneal
E. Cardiac valves
The kidney is highly susceptible to HLA mismatches and hyperacute rejection may occur in patients with IgG
anti HLA Class I antibodies. The liver is at far lower risk of rejection of this nature. Although the heart is
susceptible to HLA mismatch the cardiac valves are less prone to this effect. Corneal and skin grafts are
reasonable interchangeable between donor and recipients.

Question 13 of 20
Which of the following is not true of hyper acute solid organ transplant rejection?
A. Onset in the peri operative phase.

B. May occur as a result of blood group A, B or O incompatibility.

C. May be due to pre existing anti HLA antibodies.
D. On biopsy will typically show neo intimal hyperplasia of donor
arterioles.
E. Complement system activation is one of the key mediators.
These changes are more often seen in the chronic setting. Thrombosis is more commonly seen in the hyperacute
phase.

Question 14 of 20
You review a 42-year-old woman six weeks following a renal transplant for focal segmental glomerulosclerosis.
Following the procedure she was discharged on a combination of tacrolimus, mycophenolate, and prednisolone.
She has now presented with a five day history of feeling generally unwell with anorexia, fatigue and arthralgia.
On examination she has a temperature of 37.9 and has widespread lymphadenopathy. What is the most likely
diagnosis?
A. Hepatitis C
B. Epstein-Barr virus
C. HIV
D. Hepatitis B
E. Cytomegalovirus
Cytomegalovirus is the most common and important viral infection in solid organ transplant recipients
Primary infection with CMV typically occurs 6 weeks post transplantation in a seronegative individual who
receives an organ from a seropositive donor. Symptoms may occur as early as 20 days but can occur up to 6
months post transplant . Symptoms are often vague, retinitis can be pathognomonic, but is rarely seen in the
transplant population. CMV disease is seen in 8% of renal transplant patients. Intravenous ganciclovir is the
treatment of choice in such patients. Unfortunately, relapses are not uncommon.

Question 15 of 20
A 43 year old lady is recovering following a live donor related renal transplant. She has significant abdominal
pain. Which of the following analgesic drugs should be avoided?
A. Paracetamol
B. Morphine

C. Nefopam
D. Diclofenac
E. Co-codamol
Non steroidal anti inflammatory drugs may be nephrotoxic and therefore are usually avoided in patients who
have undergone renal transplants. Paracetamol and morphine are metabolised predominantly in the liver. There
is some renal contribution to morphine metabolism and excretion and the drug should be administered in
reduced doses or avoided if the transplanted kidney stops functioning.

Question 16 of 20
A 52 year old male attends renal transplant clinic for a post operative assessment. You note that he is on
ciclosporin and that a recent blood test shows that the ciclosporin level is elevated. Which of the following is a
recognised side effect of ciclosporin?
A.

Hyperthyroidism

B.

Diabetes

C.

Alopecia

D.

Hypothermia

E.

Nephrotoxicity

Ciclosporinnephrotoxicity
This patient is at risk of nephrotoxicity and should be referred to the renal team as soon as possible. Alopecia is
associated with azathioprine and diabetes is associated with tacrolimus.
Organ transplantation: immunosupressants
A number of drugs are available which help to mitigate the processes resulting in acute rejection. Cyclosporin
and tacrolimus are commonly used drugs.
Example regime

Initial: ciclosporin/tacrolimus with a monoclonal antibody

Maintenance: ciclosporin/tacrolimus with MMF or sirolimus
Add steroids if more than one steroid responsive acute rejection episode

Ciclosporin

Inhibits calcineurin, a phosphotase involved in T cell activation

Nephrotoxic

Monitor levels

Azathioprine

Metabolised to form 6 mercaptopurine which inhibits DNA synthesis and cell division
Side effects include myelosupression, alopecia and nausea

Tacrolimus

Lower incidence of acute rejection compared to ciclosporin

Also less hypertension and hyperlipidaemia
However, high incidence of impaired glucose tolerance and diabetes

Mycophenolate mofetil (MMF)

Blocks purine synthesis by inhibition of IMPDH

Therefore inhibits proliferation of B and T cells
Side-effects: GI and marrow suppression

Sirolimus (rapamycin)

Blocks T cell proliferation by blocking the IL-2 receptor

Can cause hyperlipidaemia

Monoclonal antibodies

Selective inhibitors of IL-2 receptor

Daclizumab
Basilximab

Question 17 of 20
A 48 year old women with end stage renal failure is undergoing a live donor renal transplant. The surgeon
decides to implant the kidney in the left iliac fossa via a Rutherford Morrison incision. To which of the
following vessles should the transplanted kidney be anastomosed?
A. Aorta and inferior vena cava
B. Internal iliac artery and vein
C. Common iliac artery and vein
D. External iliac artery and vein
E. Inferior epigastric artery and vein

First time renal tranplants and typically implanted in the left or right iliac fossae. The vessels are usually joined
to the external iliac artery and vein as these are the most easily accessible. The Rutherford Morrison incision
provides access to the external iliac vessels.

Question 18 of 20
A 28-year-old female undergoes a renal transplant for focal segmental glomerulosclerosis. Within hours of the
operation the patient becomes unwell with features consistent with severe systemic inflammatory response
syndrome. The patient is immediately taken back to theatre and the transplanted kidney is removed. What type
of immunoglobulins are responsible for the graft rejection?
A. IgE
B. IgM
C. IgG
D. IgD
E. IgA
Hyperacute graft rejection is due to pre-existent antibodies to HLA antigens and is therefore IgG mediated

Question 19 of 20
A 38 year old man is recovering following a live donor related renal transplant. The surgeon prescribes
corticosteroids to reduce the risk of graft rejection. Which of the following will not occur as a result of their
administration?
A. Suppression of macrophage activation
B. Reduction of expression of major histocompatability complex
antigens on the graft
C. Reduction in the proliferation of lymphocytes
D. Necrosis of activated lymphocytes
E. Reduction of expression of endothelial cell adhesion molecules
Corticosteroids at higher doses are able to induce apoptosis of activated lymphocytes. Necrosis is a different
process and not induced by steroids.

Question 20 of 20
A 52 year old female underwent a cadaveric renal transplant and recovers well post operatively. Her

immunosupression regime consists of tacrolimus. Which of the substances listed below should be avoided?
A. Paracetamol
B. Apple juice
C. Penicillin
D. Prune juice
E. Grapefruit juice
Tacrolimus is metabolised by the P450 enzyme system. This is inhibited by a number of naturally occurring
substances, these include grapefruit, watercress and St.Johns Wort. These should all be avoided in
immunosupressed patients taking tacrolimus.