Transplant

Goal of transplation:

prolong patient and graft survival

improve quality of life

Allograft:

transplant of an organ from one individual to another of the same species with different genotype

Autograft:

transplant from the same patient from one site of the body to another

Isograft:

a transplant from a genetically identical donor

Organ transplant type:

kidney

liver

heart

lung

pancreas

What does rejection of a transplant lead to?

graft failure

graft support

removal of the graft

What is done prior to the transplant to prevent rejection?

HLA cross matching

ABO blood group matching

Panel reactive antibody ( high PRA score can indicate the risk of rejection

What is done intra-op and post transplant to prevent rejection?

immunosuppressive medications

What can happen if a patient receives too much immunosuppression from the medications?

infection and malignancy

What can happen if the patient does not receive enough immunosuppression?

it can lead to rejection

Blood group A: donates to

A

AB

Blood group A: receives from

A

O

Blood group B: donates

B

AB

Blood group B: receives from

A

AB

B

O

Blood group B is referred to as:

universal recicipient

Blood group O: donates to

A

B

AB

O

Blood group O: receives from

O

Blood group O is referred to as:

universal donor

Induction:

given immediately before or at the time of transplant

Maintenance immunosuppression:

given chronically after transplant

Rejection immunospurression:

given if the body starts to fight off the graft

What are the types of medications used for induction immunosupression?

polyclonal antibody

monoclonal antibody

Antithymocyte globulin:

a polyclonal antibody used in induction immunosuppression

used for induction and treatment

Atgam (Equine)

Thymoglobulin (rabbit)

T cell depletion effects

given to patients at high risk of rejection

Basiliximab:

interleukin 2 receptor (IL-2) antagonist

it is a monoclonal antibody

Induction ( patients at a low risk of rejection)

Alemtuzumab:

monoclonal antibody

bind to CD52 on T cells leading to T cell depletion

Can be used off label for induction

Boxed warnings for antithymocyte and Basiliximab:

administer under the supervision of a physician experienced in immunosuppressive therapy

What is a boxed warning specific to antithymocyte globulin?

anaphylaxis

inter dermal skin testing recommended prior to 1st dose of Atgam

Side effects of antithymocyte globulin:

infusion related reactions/cytokine release syndrome ( fever and chills, rash, hypotension)

infections

leukopenia

thrombocytopenia

How do you lessen infusion related reactions caused by antithymocyte globulin?

premedicate (diphenhydramine, acetaminophen, steroids)

administer infusion over 4-6 hours

Monitoring for antithymocyte globulin:

CBC with differential

vital signs

lymphocyte profile

Counseling and administration of antithymocyte globulin:

infuse with an in line filter

normal equine doses are approximate 10 fold greater than rabbit product

atgam: 5-15 mg/kg/day

thymoglobulin: 1-1.5 mg/kg/day

Side effects of basiliximab:

hypertension

fever

nausea and vomiting

peripheral edema

dyspnea

tremor

Monitoring for basiliximab:

signs and symptoms of hypersensitivity

Contraindications: systemic steroids for immunosuppression

live vaccines

serious systemic infections

What drugs are given as maintenance immunosuppression?

calcineurin inhibitor: cyclosporine or tacrolimus or costimulation blocker: belatacept

+ anti proliferative agent: (azathioprine or mycophenolate) or mammalian target of rapamycin kinase inhibitor: everolimus or sirolimus ± systemic steroid (prednisone)

MOA of belatacept:

binds to CD80/86 on APC preventing t cell costimulation, activation, proliferation, and rejection

it does not directly bind to T cells

MOA of cyclosporine and tacrolimus:

calcineurin inhibitors preventing the transcription of cytokines and prevents t cell proliferation and activation

Boxed warnings for transplant drugs:

infection risk

cancer risk

only experienced prescribers should give these medications

Boxed warnings for cyclosporine and tacrolimus:

malignancy

infection

Cyclosporine specific boxed warnings:

malignancy

infection

nephrotoxicity

hypertension

non modified and modified formulations are not AB rated ( they are not interchangeable)

Side effects common to cyclosporine and tacrolimus:

electrolyte disturbances

hyperglycemia

hyperlipidemia

infections

nephrotoxicity

neurotoxicity

Side effects specific to cyclosporine:

gingival hyperplasia

hirustism

Side effects specific to tacrolimus:

alopecia

Monitoring for cyclosporine and tacrolimus:

trough levels (taking 30 minutes before next does is due)

Cyclosporine formulations:

non-modified: sandimmune

modified: neoral, gengraf ( increase bioavailability)

How do you administer IV cyclosporine?

non PCV sets should be used H

How do you administer oral liquid cyclosporine?

do not administer from a plastic or styrofoam cup

How do you administer tacrolimus?

do not take with food because it can decrease absorption

How do you administer IV tacrolimus?

continuous infusion

must use non-PVC bag and tubing

Counseling point for all immunosuppresants:

take exactly as prescribed

take medication after you had your blood drawn but not before

increase the risk of infection

increase risk of cancer ( use sunscreen)

many drug interactions ( report all medications to transplant doctor )

Cyclosporine counseling point:

different brands ( know what you are taking, do not switch )

cyclosporine oral solution ( do not use in styrofoam or plastic cup, use measuring device provided ( do not rinse before or after use ( wipe it down), mix with orange juice)

check blood pressure

take care of gums and teeth ( can cause gingival hyperplasia)

avoid grapefruit ( fruit and juice)

Tacrolimus counseling points:

takes as directed: once a day or every 12 hours

take on an empty stomach

monitor BP and BG

avoid grapefruit ( fruit and juice)

Side effects of azathioprine:

myelosuppression

gi side effects

acute pancreatitis

rash

hepatotoxicity

Monitoring for azathioprine:

liver function

CBC

renal funciton

boxed warning for mycophenolate:

malignancies

infections

embryo-fetal toxicity

Mycophenolate side effects:

gi side effects

leukopenia

monitoring for mycophenolate:

CBC

gi intolerance

pregnancy test

renal function

liver function

signs of infection

True/False; CellCept and Myfortic are interchangeable

False: they are not interchangeable

CellCept IV is stable in:

D5W only

Counseling points for mycophenolate:

different brands: CellCept and myfortic are not interchangeable

avoid in pregnancy

can cause diarrhea

avoid antacids containing aluminium and magnesium because they can interact with mycophenolate

Side effects of mTOR kinase inhibitors:

hyperlipidemia

hyperglycemia

hypertension

impaired wound healing

pneumonitis

peripheral edema

Monitoring parameters of mTORKinase Inhibitors:

trough levels

renal function

liver function test

lipids

BG

BP

CBC signs of infection

Boxed warnings for belatacept:

increased risk of post transplant lymphoproliferative disorder ( use in EBV) seropositive patients only)

increased risk of infection and malignancy

increased risk of TB ( test for and treat latent TB prior to use)

Side effects of belatacept:

anemia

leukopenia

UTIs

headache

peripheral edema

Monitoring for belatacept:

TB screening

EBV status

neurological signs ad symptoms

infections

Steroids in solid organ transplantation:

conversion- methylprednisolone IV to prednisone PO

steroid minimization; induction allows minimization of dose

early corticosteroid withdrawal- low immunologic risk and T-cell depleting induction

not given as monotherapy

prednisone dosing in transplant:

2.5-20 mg by mouth daily or on alternate days

shor term side effects of steroids:

increased appetite/weight gain

fluid retention

emotional instability

insomnia

stomach upset

hypertension

hyperglycemia

long term side effects of steroids:

adrenal suppression/cushing syndrome

acne

moon face

fat deposits

impaired wound healing

hypertension

diabetes

osteoporosis

impaired growth in children

induction immunosuppression treatment

monoclonal antibody ( basiliximab) or polyclonal antibody (antithymocyte) + high dose steroids

maintenance immunosuppression treatment:

1st line: tacrolimus + mycophenolate ± prednisone

alternative: belatacept , aziathoprine (can be used in pregnant) or mTOR kinase inhibitors( if patient is having intolerable side effects to mycophenolate)

CNI drug interactions:

CYP3A4 and P-GP substates

decreased levels by CYP3A4 and P-gp inducers

increased levels with CYP3A4 and P-GP inhibitors

do not use simvastatin or lovastatin with cyclosporine

mycophenolate drug interctions:

decrease the levels of hormonal contraceptives

decreased levels of mycophenolate by antacids containing aluminum/magnesium, bile acids, rifampin

Azathioprine drug interactions:

avoid using with allopurinol or febuxostat

Acute Cellular rejection treatment approach

optimized maintenance immunosuppression

high dose corticosteroids

Antibody mediated rejection treatment approach;

high dose steroids

plasmapheresis + IVIG

rituximab

symptoms of acute rejection:

chills

body aches

nausea

pain and tenderness on graft site

heart transplant patients: heart failure symptoms

kidney transplant patients: fluid retention, decreased urine output

how do you reduce injection risk in transplant patients?

infection prophylaxis: 1st 6 months and after treatment or acute rejection

infection control: proper handwashing and aseptic techniques, self monitor for infections

How can you reduce the risk of cancer in transplant patients?

screen for cancer prior to transplant

after transplant: wear sunscreen, sun protection measures

Which type of vaccines should not be given to transplant patients?

live vaccines

Pre transplant vaccination:

vaccination evaluated

all recommended vaccines given

live vaccines given at this time

Post transplant vaccines:

inactivated vaccines( > 3-6 months)

can not give live vaccines

common live vaccines: micro vy

MMR II

flumist

cholera

rotavirus

oral typhoid

varicella

yellow fever

Varicella vaccine:

give pre-transplant

vaccinate close contacts

Vaccines transplant patients should receive:

influenzae

pneumococcal vaccine; PCV20 ×1 dose or PCV 15 ×1 dose and PPSV 23 ×1 dose >8 weeks after 1st dose of PCV 15