- Fewer and less than polyclonal antibodies - No cytokine release syndrome

Transplant Flashcards by BJ Jar

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)

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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

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List induction agents

Basiliximab
ATGAM (equine)/ATG (rabbit)
Methylprednisolone IVPB
Mycophenolate (MMF)

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Basiliximab MOA

Blocks IL-2 receptor on ACTIVATED T-Lymphocytes

Signal 3 blocker

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Dosing for basiliximab

20mg IVPB on

POD0 and POD4

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Basiliximab ADEs

Fewer and less than polyclonal antibodies

- No cytokine release syndrome

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Cytokine Release Syndrome

Fever, chills, malaise
ADE of ATG

-Can minimize CRS by premedicating with:
Methylprednisolone, APAP, and diphenhydramine

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ATG ADEs

Cytokine Release Syndrome
Leukopenia, Thrombocytopenia
Skin rash, serum sickness

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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

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A transplant of tissue from one to oneself

Autograft

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A transplant from a genetically non-identical member of the same species

Allograft

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Organs or tissues are transplanted from a donor to a genetically identical recipient (identical twin)

Isograft (Syngenic transplant)

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A transplant of organs or tissues from one species to another

Xenograft (Xenogenic transplant)

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Organization that writes all the rules for transplants (governing recovery, matching, distribution, translation, data collection, and waiting list)

Organ Procurement and Transplantation Network (OPTN)

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Non-profit that carries out regulations regarding transplants

United Network for Organ Sharing (UNOS)

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OPO for Arkansas

Arkansas Regional Organ Recovery Agency (ARORA)

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Order of writing to governing organ transplants in Arkansas

OPTN - write regulations
UNOS - carries out regulations and monitor OPOs
ARORA - training, management, community involvement

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Types of solid organ transplants

Kidney
Liver
Pancreas
Heart - deceased
Small Bowel
Lungs - deceased

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A chain of donors created to swap organs for a loved one

Usually all at the same time

Paired donation

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Donation just to be nice

Altruistic donor

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Common causes of kidney organ failure

Diabetic nephropathy
Hypertension
Glomerulonephritis
Polycystic Kidney Disease

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Common causes of liver organ failure

Alcoholic Liver Disease
Hepatitis B &amp; C
Hepatic Tumors
Metabolic Disorders
Cryptogenic cirrhosis
Polycystic Liver Disease

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Common causes of pancreas organ failure

Diabetes

Pancreatic tumor

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Common causes of heart organ failure

Cardiomyopathy
Coronary Artery Disease
Congenital Disease

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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

1. ABO Blood Testing x2 2. HLA (MHC) Matching (Kidney only) 3. Final Crossmatching 4. 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

1. ABO Typing x2 2. HLA (MHC) matching in kidneys Then, right before transplant... 3. Final Crossmatch 4. 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