Renal: Transplants

Question 1

Describe the two immunological compatibility issues when it comes to transplantation [2]

Answer 1

Blood groups
HLA

Question 2

The risk of which cancers is he most at risk of following renal transplantation? [1]

Answer 2

The risk of all skin cancers increases following kidney transplantation, evidence has shown that in particular the risk of squamous cell carcinoma is increased.

Question 3

Which type of GN is associated with renal transplants? [1]

Answer 3

Focal sclerosis glomerulosclerosis

Question 4

With regards to acute rejection of transplants, how would you detect antibody prescence? [1]

Answer 4

Detect antibody presence with complement: C4d
* The antibody-antigen complex activates the compliment system
* This produces C4d molecules (which forms covalent bonds with endothelial cells)
* C4d molecules are stained easily
* This shows that acute rejection has occurred

Question 5

What are two mechanisms that acute rejection occurs? [2]
(probably don’t learn that much)

Acute rejection can be either via:

Answer 5

Acute Cellular Rejection (ACR)
- Cytotoxic T lymphocyte response
- Macrophage response

OR

Acute Antibody Mediated Response (AMR)
- B lymphocyte response making antibodies (agaisnt MHC Class 1 /2 antigens or ABO blood group antigens)

Question 6

Describe the causes of chronic kidney transplant graft failure [2]

Answer 6

Both antibody and cell-mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)

Question 7

Describe the features of acute graft failure:
- Why does it usually occur? [2]
- How does it present? [3]
- Prognosis? [2]

Answer 7

• usually due to mismatched HLA; also caused by CMV infection
• usually asymptomatic and is picked up a rising creatinine, pyuria and proteinuria
• potentially reversbile with steroid and immunosuppressant

Question 8

What are the sites of action used for immunosuppressive drugs? [3] and what drugs used? [5]

Answer 8

Calcineurin inhibitors:
* Calcineurin is an enzyme that activates T-cells of the immune system.
* E.g. Cyclosporin and tacrolimus

Anti-proliferative drugs:
* (target nucleus at end stage of T cell activation)
* e.g. Azathioprine and Mycophenolic acid

Prevent cytokine (IL-2) gene activation
* Use cortiosteroids
* e.g. Prednisolone

Rapamycin: stops clonal expansion of T cells

Question 9

Explain how can you prevent acute rejection of transplants? [2]

Answer 9

HLA matching (make sure that not positive for match)

Minimising ischaemia-reperfusion injury:
* Ischaemia causes upregulation of adhesion molecules, which increases adhesion of leukocytes when blood is reperfused.
* More leukocytes increases chance of rejection, SO try and limit ischaemia time.
* Cold ischaemia time: 12 hrs
* Warm ishaemia time: 1 hour

Question 10

How can we prevent hyperacute rejection? [3]

Answer 10

Use somone who is ABO compatabile (O is universal donor)

screen for preformed antibodies:
* Direct cross match: mix donor cells and recipient serum. Look for complement activation (positive is bad)
* Beads with bound HLA: look to see if recipient serum binds to HLA beads
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Question 12

State 3 reasons why hyperacute rejection of a transplant may occur [3]

Answer 12

Previous transplant: presence of antigen on the transplant that has already been seen on previous transplant. HLA protein common to both transplants but not seen in the recipient

Previous pregnancy: if foetal blood escapes into circulation. Paternal antigens can prime the mothers immune system

Previous blood transfuison: HLA antigen in blood, when transplant occur causes hyperacute immune response

Question 13

Describe the features of hyperacute rejection [3]

Answer 13

• Happens within minutes to hours of transplant
• Occurs due to pre-exisiting antibodies agaisnt ABO or HLA antigens (that have already been pre-activated)
• Leads to neutrophil inifiltration, intravascular coagulation and cortical necrosis

Question 14

What is delayed graft function (DGF)? [1]
What does the risk of DGF increaese with? [1]

Answer 14

Delayed graft function (DGF) is defined by the need for dialysis in the first week after transplantation.

Risk increases with prolonged WITs and CITs (therefore is relatively rare with living donor grafts). Whilst most DGF kidneys eventually function, there is a recognised association with increased rejection rates and decreased graft survival rates.

Question 15

Describe the AEs of the following drugs used in kidney transplantation:

• Immunosuppressants [2]
• Tacrolimus [1]
• Cyclosporine [1]
• Steroids [1]

Answer 15

• Immunosuppressants cause seborrhoeic warts and skin cancers (look for scars from skin cancer removal)
• Tacrolimus causes a tremor
• Cyclosporine causes gum hypertrophy
• Steroids cause features of Cushing’s syndrome

Question 16

Two doses of which drug are given after a transplant to prevent acute rejection [1]

Answer 16

Basiliximab is a monoclonal antibody targeting the interleukin-2 receptor on T-cells.

Question 17

What increases the chance of having better kidney transplant outcomes?

Answer 17

Patient and donor kidneys are matched based on the human leukocyte antigen (HLA) type A, B and C.

They do not have to match fully, but the closer the match, the less likely there is organ rejection and the better the outcomes.

Recipients can receive treatment to desensitise them to the donor HLA in preparation for a transplant from a living donor.

Question 18

Which infections can occur secondary to immunosuppressant medication? [3]

Answer 18

Pneumocystis jiroveci pneumonia (PCP/PJP)
Cytomegalovirus (CMV)
Tuberculosis (TB)

Question 19

State complications related to immunosuppressants w/ kidney transplants [5]

Answer 19

Ischaemic heart disease

Type 2 diabetes (steroids)

Infections are more likely, more severe and may involve unusual pathogens:
- Viral, e.g. cmv and warts (CMV affects 8-10% of all transplant recipients
- Bacterial infection especially of the urine (40-50% of female transplant recipients)
- Fungal infections such as pneumocystis

Non-Hodgkin lymphoma

Skin cancer (particularly squamous cell carcinoma)

Question 20

State complications that can occur relating to transplant [3]

Answer 20

Transplant rejection (hyperacute, acute or chronic)
Transplant failure
Electrolyte imbalances

Question 21

When HLA matching for a renal transplant the relative importance of the HLA antigens are as follows []

Answer 21

When HLA matching for a renal transplant the relative importance of the HLA antigens are as follows DR > B > A
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Question 22

Explain what needs to happen for HLA antibodies to present? [1]

Answer 22

:Not naturally occuring: need a sensitising event: pregnancies; blood transfusion; previous transplants

Question 23

Where do you find HLA Class I and HLA Class II cells? [2]

Describe the role of HLAs

Answer 23

HLA Class I is present on most cells in the body
HLA Class II is expressed on APCs and B cells, or some cells which are activated or injured

Role:
* HLA is responsible for presenting antigens to T cell receptor
* The T cell ‘sees’ the antigen sat in the groove of the HLA protein

Question 24

State the two classes of HLA [2]

Answer 24

HLA Class I:
- HLA A
- HLA B

HLA Class II
- HLA DR

Question 25

Answer 25

Question 26

Answer 26

Question 27

Name two monoclonal antibodies used as immunosuppressants in kidney transplant [2]

What is their MoA? [1]

Answer 27

Basilixumab
Daclizumab

Selectively block T cells via CD-25

Question 28

Basilixumab
Daclizumab

Are two monoclonal antibodies used in kidney transplants. When are they administered? [1]

Answer 28

Given immediately after transplant: ‘induction’

Question 29

Which drug class of immunosuppressants are at risk of creating NODAT (new-onset diabetes after transplantation)? [1]

Answer 29

Calcineurin inhibitors (tacrolimus & ciclosporin)

Question 30

What is the first choice treatment for acute rejection of transplant? [1]

Answer 30

Prednisolone

Question 31

To decrease infection risk, prophylaxis drugs for which two pathogens are given? [2]

Answer 31

CMV
Pneumocysitis jirovecii

Question 32

What impact does kidney transplant have on CVD? [2]

Answer 32

3-5 increasae if premature CVD compared to general pop (but 80% less that dialysis
NODAT
BP increase