Transplant Flashcards
CI to donating organs
70 CHIMPS 70+ years old CKD HIV+, Hep B SA+, Severe HTN IVDA (current user) Metastatic Malignancy (potential) Prolonged warm ischemia Sepsis (untreated, bacterial)
CI to receiving organs
COUSINS or COPS SIN Cancer/Malignancy Obesity (BMI above 35) Uncontrolled Psych Disorder Social Support Absent Infection (uncontrolled) Noncompliance Substance Abuse
List induction agents
Basiliximab
ATGAM (equine)/ATG (rabbit)
Methylprednisolone IVPB
Mycophenolate (MMF)
Basiliximab MOA
Blocks IL-2 receptor on ACTIVATED T-Lymphocytes
Signal 3 blocker
Dosing for basiliximab
20mg IVPB on
POD0 and POD4
Basiliximab ADEs
- Fewer and less than polyclonal antibodies
- No cytokine release syndrome
Cytokine Release Syndrome
Fever, chills, malaise
ADE of ATG
-Can minimize CRS by premedicating with:
Methylprednisolone, APAP, and diphenhydramine
ATG ADEs
Cytokine Release Syndrome
Leukopenia, Thrombocytopenia
Skin rash, serum sickness
Monitoring for polyclonal antibodies
ATG/ATGAM:
CBC with diff and vitals during admin
Everybody Appreciates Toilet Paper
Efficacy - ALC (lymphs,auto% x WBC)
Less than 50 - Hold
50-100 decrease dose by 1/2
Toxicity - Platelets
Less than 50,000 - Hold
50k-100k - decrease dose by 1/2
A transplant of tissue from one to oneself
Autograft
A transplant from a genetically non-identical member of the same species
Allograft
Organs or tissues are transplanted from a donor to a genetically identical recipient (identical twin)
Isograft (Syngenic transplant)
A transplant of organs or tissues from one species to another
Xenograft (Xenogenic transplant)
Organization that writes all the rules for transplants (governing recovery, matching, distribution, translation, data collection, and waiting list)
Organ Procurement and Transplantation Network (OPTN)
Non-profit that carries out regulations regarding transplants
United Network for Organ Sharing (UNOS)
OPO for Arkansas
Arkansas Regional Organ Recovery Agency (ARORA)
Order of writing to governing organ transplants in Arkansas
OPTN - write regulations
UNOS - carries out regulations and monitor OPOs
ARORA - training, management, community involvement
Types of solid organ transplants
Kidney Liver Pancreas Heart - deceased Small Bowel Lungs - deceased
A chain of donors created to swap organs for a loved one
Usually all at the same time
Paired donation
Donation just to be nice
Altruistic donor
Common causes of kidney organ failure
Diabetic nephropathy
Hypertension
Glomerulonephritis
Polycystic Kidney Disease
Common causes of liver organ failure
Alcoholic Liver Disease Hepatitis B & C Hepatic Tumors Metabolic Disorders Cryptogenic cirrhosis Polycystic Liver Disease
Common causes of pancreas organ failure
Diabetes
Pancreatic tumor
Common causes of heart organ failure
Cardiomyopathy
Coronary Artery Disease
Congenital Disease
Common causes of small bowel organ failure
Small Bowel Syndrome
Common causes of lungs organ failure
Cystic Fibrosis
Idiopathic Pulmonary Fibrosis
Primary Pulmonary Hypertension
COPD, emphysema
The organ transplant waiting list is ____ compared to the number of donors
3-5 times higher
Allograft rejection depends on:
Antigen recognition
Activation of T-Cells
Proliferation of T-Cells
Complement mediated and occurs immediately
upon revascularization of the transplanted organ
Hyperacute Reaction
Caused by infiltration of the allograft by T cells
which causes inflammatory and cytotoxic effects on
the graft
Acute Rejection
-relatively easy to treat
Caused by antibodies directed against the vascular
endothelium of the transplanted organ
Vascular Rejection (Humoral Rejection)
-more difficult to treat than cellular rejection, but is
usually responsive
Caused by complex interactions of cytokines, cellular
interactions, CD4+ and CD8+ T cells, and B cells
Chronic Rejection
-difficult to treat and will ultimately result in graft loss
Rejection Process
-Recognition of donor Major Histocompatibility
Complex (MHC) differences by the recipients
immune system
- Recruitment of activated lymphocytes
- Initiation of immune effector process
- Graft destruction
Occurs when preformed donor-specific antibodies are present in the recipient’s blood at the time of transplant.
Recipient IgG antibodies bind to donor vascular endothelium
Tissue damage occurs through
1. antibody-dependent cytotoxicity
2. complement cascade
Ischemic damage to microvasculature rapidly produces tissue necrosis
Hyper acute rejection
Metabolic disorders cause what type of organ failure?
Liver
HTN causes what type of organ failure?
Kidney
Diabetes causes what type of organ failure?
Pancreas
Chronic rejection is caused by
Caused by complex interactions of cytokines, cellular interactions, CD4+ and CD8+ T cells, and B cells
Prevention of hyperacute rejection
- ABO Blood Testing x2
- HLA (MHC) Matching (Kidney only)
- Final Crossmatching
- Panel Reactive AntiB (Kidney only)
Type A blood is compatible with…
B…
AB…
O…
A and O
B and O
A, B, AB, and O
O only
How does final cross matching work
Donor and recipient blood are mixed.
If anticoag occurs, crossmatch is positive.
-means hyperacute rejection would occur
-transplant cancelled
How does PRA work
Panel Reactive AntiB represents the percentage of population that the recipients blood has antiBs to and will react with. Pts develop anti-HLA antiBs through: 1. Pregnancy 2. Other transplants 3. Blood Transfusions
High PRA protocol
If current PRA is 30+ or history of 50+, Induce with ATG 2mg/kg d0, d1, and d3 Alternatives: -Rituximab -IVIG -Immunoadsorption columns -Bortezomib
Tx of acute rejection
Corticosteroids
-Methylprednisolone 500 IV x3 days
-followed by PO prednisone taper
Stops immune mediated attack of tissues
Second line ATG/ATGAM for steroid resistant
Tx of chronic rejection
None
Not reversible
Second line tx for acute rejection
Polyclonal antiBs (ATG or ATGAM)
for steroid resistant rejection
Premedicate with CCS, Tylenol and Benadryl
Tx for vascular (humoral) rejection
Plasmapheresis with IVIG Plasmapheresis alone High-dose IVPB Methylprednisolone Antithymocyte globulin Cyclophosphamide Rituximab Bortezomib
Four Types of Rejection
Hyperacute Rejection - PREFORMED antibodies - no tx, must prev Acute Cellular Rejection - easy tx Vascular/Humoral Rejection Chronic Rejection - slow prog, no tx
Universal recipient
Universal donor
Type AB
Type O
Which HLAs do we look at for kidney transplants?
HLA-A
HLA-B
HLA-DR
Ideal HLA matching
Zero mismatches
How many HLA matches do you need to transplant?
A two antigen match is enough to transplant. Six would be best (zero mismatches)
How many antigens does each HLA have?
Each HLA-A has
2 antigens per donor and recipient
Each HLA-B has 2 each
Each HLA-DR has 2 each
Order or prevention steps for hyperacute rejection
- ABO Typing x2
- HLA (MHC) matching in kidneys
Then, right before transplant… - Final Crossmatch
- Panel Reactive Antibody (PRA) x2
HLA matching occurs only in
Kidney transplants only
What is the big test to prevent hyperacute rejection?
Final Crossmatch
Between T and B cells
Expressed as + or -
If coagulase, then + and rejection
What does a PRA of 40 tell you?
A pt has antibodies to 40% of tissue types expressed in a given population (donor pool).
It also tells you that the pt has a 40% chance of rejection.
How does PRA go up?
Previous transplants
Blood transfusions
Pregnancy
(PRA can fluctuate over time)
Most common form of rejection
Acute rejection
T-lymphocytes attack the allograft
Role of T helper cells
Recruit other immune cells
CD-8 and B cells
Second line tx of acute rejection
ATG or ATGAM for steroid resistance
-big guns that actually kills T cells instead of inhibiting them
Acute Rejection vs. Drug Toxicity
Acute Rejection
- within 4 weeks
- fever
- graft swelling/pain
- rapid rise in SrCr
- Normal CSA or TAC conc.
- Decreased urine output
Drug Toxicity
-good urine output, afebrile,elevated drug conc, greater than 6 weeks
Rejection driven by MHC II
Humoral or Vascular or Antibody Mediated Rejection
Tx for humoral/vascular/antibody mediated rejection
Plasmapheresis w IVIG Methylprednisolone Cyclophosphamide Rituximab Bortezomib
Other names for vascular rejection
Humoral Rejection
Antibody Mediated Rejection
Antibody Mediated Rejection usually occurs… (time)
Within 3 months
