Solid Organ Transplant Pharmacotherapy and Management Flashcards
What is autotransplantation?
Transplant of tissue from 1 part of the body to another
What is allotransplantation?
Transplant of tissue from 1 person to another person
What is xenotransplantation?
Transplant of tissue from a different species
What is orthotopic?
Transplanted into recipient in the same place (ex. heart, lung)
What is heterotopic?
Transplanted into recipient in a different place (ex. kidney)
What is a living donor?
- Kidneys or Livers
- Related or Unrelated
- Directed or Non-Directed
- Kidney Paired Exchange
What is a deceased donor?
- Deceased by Brain Death (DBD)
- Primary brain death with intact
cardiac and respiratory function - Organs are perfused until the time of procurement
- Deceased by Circulatory Death (DCD)
- Does not meet brain death criteria
- Non-heart beating donation
What is the pre-transplant immunologic evaluation and management?
ABO blood group antigens
HLA typing
HLA antibodies
panel reactive antibody
crossmatch
ABO blood group antigens
blood type compatibility
group O = universal donor (b/c no antigens)
group AB = universal recipient (b/c no antibodies)
HLA typing
- Major Histocompatibility Complex (MHC) / Human Leukocyte Antigen (HLA) Complex
- An association of genes found on short arm of chromosome 6 that playan important role in immune recognition and response
- Distinguishes “self” from “non-self”
- Antigen presenting structures for T cells
- HLA compatibility assessed by number of HLA mismatches (or matches) of the donor
HLA antibodies
- Do NOT occur naturally (recipient forms antibodies against a donor organ)
- Formed in response to non-self HLA
exposure - “Sensitizing events”
- Pre-transplant HLA donor-specific antibodies (DSA) = contraindicated in deceased donor transplants
- Post-transplant DSA: development indicates failure of immunosuppression
- “de novo DSA”
What are sensitizing events?
blood transfusions
pregnancy
previous transplant
What is the determination of panel reactive antibodies?
- Quantified as % of the panel to which the patient has developed antibody
- Value varies from 0-100% and may change over time
- The higher the PRA = increased sensitization to MHC antigens
What is the determination of crossmatch?
- Negative result must be obtained prior to transplant
- Testing the transplant recipient’s serum against donor T cells to determine if there is preformed anti-HLA Class I antibody
- It specifically checks for pre-existing antibodies in the recipient that could react against the donor’s HLA antigens.
Panel reactive antibody?
- Amount of pre-formed HLA antibodies in a recipient compared to general population
- Higher PRA = increased risk of rejection and longer wait times for an organ - >20–30% generally considered sensitized (high risk)
- PRA can be checked multiple times while patients are on the waitlist - Possible “sensitizing events”
Crossmatch
- Donor-specific HLA antibody testing
- Standard: qualitative (positive vs negative)
- Flow: quantitative (measures degree of antibody activity)
recipient lymphocytes + donor blood - Positive XM indicates pre-formed DSA present HIGH risk of rejection - Deceased donor transplant is typically CANCELLED
- May be able to overcome for living donor transplants
What are the goals of immunosuppressive therapy?
balance between rejection, toxicity, and infection
What is allograft rejection?
- Immune response causing inflammation and direct tissue destruction
- Ultimately can lead to loss of graft function
- Can occur via T-cells, B-cells, or both
What is the risk of rejection based off organ type?
lowest –> highest risk: liver, kidney/pancreas, heart, small bowel/lung
risk increases with more lymphoid tissue (more APCs transplanted with the organ)
How does age affect risk of rejection?
- Immunosenescence: gradual deterioration of immune system as age increases
- Higher risk of infections + malignancies, lower risk of rejection
- Can affect choice of induction (lymphocyte-depleting vs. non-depleting)
How does race affect risk of rejection?
- African Americans
- Greater risk of rejection
- Rapid metabolizers of tacrolimus –> Much higher dose requirements * May benefit from Envarsus (prolonged-release tacrolimus)
What are the types of allograft rejection?
T-cell mediated rejection
antibody mediated rejection
What is T-cell mediated rejection?
- Also more commonly known as acute cellular rejection (ACR)
- Infiltration of the allograft by lymphocytes and other inflammatory cells
What is antibody mediated rejection?
- Evidence of acute tissue injury
- Circulating donor- specific antibodies (DSA) produced from plasma cells
- Immunological evidence of an antibody-mediated process
