Intro to kidney transplantation Flashcards
Outline the role of immunology in graft rejection
-T cells arrange the allo-immune response after transplantation and are essential for graft rejection
Effector mechanisms of graft injury include:
- CD8+ mediated cytotoxicity
- CD4+ mediated delayed type hypersensitivity like reaction
- Antibody mediated injury
Define allograft
A tissue graft from a donor of the same species as the recipient but not genetically identical.
Outline the different types of organ donor
- Donation after brain death (DBD)
- Donation after circulatory death
- Living donation
- Expanded criteria (EC) donors
What are the barriers for transplantation?
- ABO antigens
- HLA antigens
- Preformed anti-HLA antigens
Outline what testing needs to be done prior to kidney transplantation
- HLA antigens(donor/recipient)-matching not required
- Preformed anti-HLA abs against donor(pregnancy, transfusion, prior transplant)
- ABO compatibility (A2 less antigenic: <1.8titers)
What are the challenges faced in transplantation
- Significant decrease in rates of early acute rejection
- Little substantial improvement in long-term allograft and patient survival
- Requirement for use of more marginal grafts, older donors & immunologically sensitized recipients with higher co-morbidity
Explain the principles of Donor-Recipient matching in kidney transplantation
- ) ABO compatibility=avoids hyperacute rejection
- Best HLA match (HLA-DR> HLA-B> HLA-A)=Reduces risk of acute rejection; improves graft survival; prevents allo-sensitisation
- ) No preformed anti-donor HLA abs (negative cross match)=avoids hyperacute rejection
- )Minimise cold ischaemia time=reduces allograft injury
Outline the characteristics of ABO antigens
- Expressed on donor kidneys
- ABO compatibility between donor kidney and recipient is as in blood transfusion(except that A2 kidney donors may be transplanted into O or B recipients if anti-A ab titres are low)
- ABO incompatible transplantation
- Blood type O are universal donors
Outline the different recipient ABO types and state…
i. ) the ABO abs on recipients’ serum
ii. )compatible ABO type of donor kidney
(1. )A
i. )=Anti B
ii. ) A or O
(2. )B
i. )= Anti A
ii. ) B or O
(3. )O
i. ) Anti A and Anti B
ii. )O only
(4. )AB
i. )=none
ii. ) All
Why is it the O negative is now only considered the universal donor
cos it doesnt contain any Rh antigen (aswell as lacking all the other antigens)
Outline the role HLA abs
- May develop after exposure to blood products, pregnancies or prior transplants
- Presence of preformed anti-HLA sb against the donor kidney is associated with a higher risk of ab mediated rejection
- A positive CDC T cell cross match is an absolute contraindication for renal transplantation
- De novo DSA post-tx is a major cause of graft loss
What is the aim of paired kidney donation
- Good solution when donor/recipient pairs are ABO or HLA incompatible
- Exchange donor transplants to improve compatibility
Outline the basic principles of immunosuppression in transplants
- Risk of acute rejection and graft loss is highest in the first 3 months &immunosuppression is at it’s highest during this period
- Serious side effects of immunosuppresive therapy (i.e. infections & malignancy) correlate with total immunosuppressive burden
- Immunosuppression tapers slowly to maintenance levels by 6-12months
State some risk factors for transplant rejection
- African american decent
- Younger
- HLA mismatch
- previous transplants
- High PRA/positive DSA
- Aggressive auto-immune disease
- Prior rejection
State examples of induction immunosuppression
- )Monoclonal abs
- Basiliximab (anti-IL2 receptor)
- Alemtuzumab(anti-CD52) - )Polyclonal abs
- Antithymocyte globulin (rabbit or horse)
State examples of maintenance immunosuppresion
- )Calcineurin inhibitors
- cyclosporin
- tacrolimus - )Purine synthesis inhibitors
- azathioprine - )Multiple
- corticosteroids - )Mammalian target of Rapamycin(mTOR) inhibitors
- sirolimus - )Fusion proteins
- Belatacept (CTLA4-Ig)
How can we prevent drug toxicity taken in transplants
- Steroid sparing regimens & steroid avoidance
- Reducing calcineurin inhibitor dose after critical post transplant period
- Calcineurin inhibitor avoidance
- Single drug regimens (higher rates of acute rejection)
Outline the general principles of post-transplant infection
- common community-acquired & rarer opportunistic infections
- Fewer symptoms, muted clinical findings, delayed clinical presentation
- May need urgent treatment
- Potential drug interactions
- Drug resistance more common
- Drug levels only crudely estimate immunosuppresive burden
Focus on disease prevention including prophylactic drugs and vaccination
also greater risk of malignancy esp skin cancer
What types of viral infections may occur post-transplant
- ) Community-acquired (eg common respiratory viruses)
- ) Latent viruses (eg HSV,CMV,VZV, Hep B& C, papillomavirus and polyomavirus)
- )Donor-derived (eg CMV,EBV,Hep B& C, HIV,rabies)
Outline acute antibody mediated rejection
- Mediated by abs against transplanted organ
- Direct ab mediated injury, complement activation and Fc-mediated toxicity
- Endothelium in peritubular capillaries and glomeruli is the primary target of alloantibodies
- Treatment includes removal of alloabs,decreased production of alloabs , and attentutation of the immune response to abs
Outline acute cellular rejection
- Mediated by lymphocytes and macrophages
- Elicited by CD 8+ mediated cytotoxicity and CD4+ mediated cytokine secretion and macrophage recruitment
- The tubulointerstitium is the main kidney compartment affected
- Treatment includes high dose of steroids or thymoglobulin/ATG
Why should mycophenolate mofetil be avoided during pregnancy/ planning for pregnancy in a transplant recipient
- It’s associated with a high risk of teratogenicity
- We use azathioprine during pregnancy as it’s the safest one
