5.2: Renal Transplantation Flashcards
Describe blood group compatibility and renal transplant?
Describe which groups can recieve what kidneys?
What happens if you give the kidney to a non-compatible recipient?
Transplants must be done that are blood group compatable
O Blood Type = O only
A Blood Type = A and O only
B Blood Type = B and O only
AB blood type = AB and O only
Anyone can recieve a type O kidney
Recieving the wrong type of kidney causes rejection leading to necrosis
What else is done (after blood group matching) to determine who is compatible with a donor kidney?
Explain how this works?
HLA Matching (Human Leucocyte Antigen Matching)
HLA are cell surface proteins expressed on cells
If they don’t match, they set up an immune response leading to rejection
What are the three HLA types?
HLA A (Class 1)
HLA B (Class 1) HLA DR (Class 2)
How many types are there for each HLA A, B and DR?
How are these inherited?
There are two types
Inherited from parents - one from mum, one from dad
Why is HLA important?
- Transplant survival
(The better matched a kidney, the more likely it is to survive)
- HLA Antibodies
If people have been exposed to certain HLA antigen in the past (Eg: Blood transfusion, pregnancy, previous transplant) they may have antibodies against it. This leads to rejection (which cannot be immunosuppressed)
Describe (in order from highest to lowest) the chance of graft survival from the following
- Mismatch Cadaver (2, 2, 2)
- Mismatch Cadaver (0, 0, 0)
- Unrelated Live Donor
- Related Live Donor
Highest chance of survival
- Related Live Donnor
- Unrelated Live Donor
- Mismatch Cadaver (0, 0, 0) - not best match
- Mismatch Cadaver (2, 2, 2) - very poor match
Describe the pathophysiology of transplant rejection?
HLA antigen binds to antigen presenting cells
This binds to T cell receptor
Activates CD4 cells (helper T cells)
- Activate CD8+ cells
- Activate NK cells
- Activate B cells
- Produces complement and cytokine
B cells produce antibody which causes cell lysis and rejection
Name the two types of rejection?
Cellular Mediated (Eg: CD8+ cells)
Antibody Mediated (Eg: B Cells)
Describe the balancing act in tissue transplant?
Need to prevent rejection
However, cannot over immunosupress patient as this can prevent suppression of infection and malignancy
By suppressing T cells and B cells this increases risk of infection and malignancy
Describe the infections/diseases in immunosuppression for transplant?
Cytomegalovirus - Viral infection most commonly seen in immunosuppressed patients, causes pneumonitis, oesophagitis, hepatitis - very unwell
Pneumocitis Pneumonia - Slowly worsening pneumonia leading to respiratory failure
Non Melanoma Skin Cancer
Transplant lymphoma
Describe the three types of rejection?
*HINT: Think about time-frame*
Hyperacute
- Due to preformed antibodies
- Cannot save kidney
- Must be removed
Acute
- T cell or B cell mediated
- Can be treated with improved immunosuppression
Chronic
- Immunological and vascular deterioation of the tissue
Describe the drugs used in immunosuppression?
Which stage are these used at?
Induction:
- Steroids
- MMF
- CyA
- Tacrolimus
- Antibodies
Consolidation:
- Steroids
- MMF
- CyA
- Tacrolimus
Maintenance:
- Steroids
- MMF
- CyA
- Tacrolimus
At what stage in the immunosuppression do most infections occur?
At the induction stage when the patient is on the highest dose of immunosuppression
What is the basis of anti-rejection therapy?
Reduces activation of T and B cells to prevent host vs transplant immune mediated response
Ideally would have good response and minimal side effects
Describe Calcineurin Inhibitors:
- Give an example?
- How do they work?
- Which of the two arms of rejection do they work on?
- Side effects?
Cyclosporin and Tacrolimus
Prevents activation of T helper cells
- Prevents direct cell killing (By Cd8+)
- Prevents cytokine release (and B cells)
So inhibits BOTH cell mediated and antibody mediated rejection
Side effects: Renal dsyfunction, Hypertension, Diabetes, Tremors
