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Inflammation block > Intro to kidney transplantation > Flashcards

Intro to kidney transplantation Flashcards

1
Q

Outline the role of immunology in graft rejection

A

-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
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2
Q

Define allograft

A

A tissue graft from a donor of the same species as the recipient but not genetically identical.

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3
Q

Outline the different types of organ donor

A
  • Donation after brain death (DBD)
  • Donation after circulatory death
  • Living donation
  • Expanded criteria (EC) donors
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4
Q

What are the barriers for transplantation?

A
  • ABO antigens
  • HLA antigens
  • Preformed anti-HLA antigens
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5
Q

Outline what testing needs to be done prior to kidney transplantation

A
  • HLA antigens(donor/recipient)-matching not required
  • Preformed anti-HLA abs against donor(pregnancy, transfusion, prior transplant)
  • ABO compatibility (A2 less antigenic: <1.8titers)
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6
Q

What are the challenges faced in transplantation

A
  • 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
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7
Q

Explain the principles of Donor-Recipient matching in kidney transplantation

A
  1. ) ABO compatibility=avoids hyperacute rejection
  2. Best HLA match (HLA-DR> HLA-B> HLA-A)=Reduces risk of acute rejection; improves graft survival; prevents allo-sensitisation
  3. ) No preformed anti-donor HLA abs (negative cross match)=avoids hyperacute rejection
  4. )Minimise cold ischaemia time=reduces allograft injury
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8
Q

Outline the characteristics of ABO antigens

A
  • 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
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9
Q

Outline the different recipient ABO types and state…

i. ) the ABO abs on recipients’ serum
ii. )compatible ABO type of donor kidney

A

(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

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10
Q

Why is it the O negative is now only considered the universal donor

A

cos it doesnt contain any Rh antigen (aswell as lacking all the other antigens)

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11
Q

Outline the role HLA abs

A
  • 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
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12
Q

What is the aim of paired kidney donation

A
  • Good solution when donor/recipient pairs are ABO or HLA incompatible
  • Exchange donor transplants to improve compatibility
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13
Q

Outline the basic principles of immunosuppression in transplants

A
  • 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
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14
Q

State some risk factors for transplant rejection

A
  • African american decent
  • Younger
  • HLA mismatch
  • previous transplants
  • High PRA/positive DSA
  • Aggressive auto-immune disease
  • Prior rejection
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15
Q

State examples of induction immunosuppression

A
  1. )Monoclonal abs
    - Basiliximab (anti-IL2 receptor)
    - Alemtuzumab(anti-CD52)
  2. )Polyclonal abs
    - Antithymocyte globulin (rabbit or horse)
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16
Q

State examples of maintenance immunosuppresion

A
  1. )Calcineurin inhibitors
    - cyclosporin
    - tacrolimus
  2. )Purine synthesis inhibitors
    - azathioprine
  3. )Multiple
    - corticosteroids
  4. )Mammalian target of Rapamycin(mTOR) inhibitors
    - sirolimus
  5. )Fusion proteins
    - Belatacept (CTLA4-Ig)
17
Q

How can we prevent drug toxicity taken in transplants

A
  • 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)
18
Q

Outline the general principles of post-transplant infection

A
  • 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

19
Q

What types of viral infections may occur post-transplant

A
  1. ) Community-acquired (eg common respiratory viruses)
  2. ) Latent viruses (eg HSV,CMV,VZV, Hep B& C, papillomavirus and polyomavirus)
  3. )Donor-derived (eg CMV,EBV,Hep B& C, HIV,rabies)
20
Q

Outline acute antibody mediated rejection

A
  • 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
21
Q

Outline acute cellular rejection

A
  • 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
22
Q

Why should mycophenolate mofetil be avoided during pregnancy/ planning for pregnancy in a transplant recipient

A
  • It’s associated with a high risk of teratogenicity

- We use azathioprine during pregnancy as it’s the safest one

Inflammation block (27 decks)

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