Organ Transplant Flashcards by Madison Denny

Indications for a Kidney transplant

Diabetes
Hypertension
Lupus
PCKD

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Indications for a liver transplant

Alcoholic cirrhosis
NASH
HBV
HCC
APAP toxicity

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Indications for Pancreas transplant

Diabetes

- Congenital abnormalitites

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Indications for Heart transplant

Ischemic heart disease
Congenital abnormalities
Idiopathic cardiomyopathy
Valvular diseases

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Indications for Lung transplant

CF
Pulmonary HTN
Pulmonary fibrosis
COPD
Emphysema

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Goals of Immunosuppression

Prevent rejection
Avoid complications
Patient and graft survival
Patient adherence

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Phases of Immunosuppression

Desensitization
Induction
Maintenance

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Least to most immunogenic organs

Liver
Kidneys
Pancreas
Heart
Lungs
Colon

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Induction Therapy Goal

Prevent early acute graft rejection

- Decrease T cells and/or B cells for months

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Drugs that can be used for induction therapy

Basiliximab
Antithymocyte globulin
Alemtuzumab

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Basliximab (Simulect) Mechanism of Action

Blocks T cell proliferation
Via interleukin 2 (IL-2)
Anti CD25 antibodies
Used in lowest immunologic risk patients

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Antithymocyte Globulin (Thymoglobulin) Mechanism of Action

Binds to T cell surface antigens
leading to depletion of T cells
Used in moderate to high immunologic risk
Increased risk of CMV, BKV, and PJP

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Alemtuzumab (Campath) Mechanism of action

Binds to CD52 on T cells, B cells, NK cells, and monocytes/macrophages
“AIDs” in a bottle
1+ year for CD4/8 counts to recover
Associated with many opportunistic infections

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Maintenance Therapy Goal

Prevent graft rejection

- Life long immunosuppression

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Drugs that can be used for Maintenance Therapy

Corticosteroids
Calcineurin inhibitors
Antimetabolites
mTOR inhibitors

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Corticosteroids mechanism of action

Inhibit cytokine gene expression
Modify lymphocyte distribution and function
Anti inflammatory
ex. prednisone 5-10mg/day

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Corticosteroid long term side effects

Osteoporosis
Adrenal insufficiency
pancreatitis
Amenorrhea
Diabetes mellitius

Corticosteroid short term side effects

-Mood change
-Hyperglycemia
-Hypertension
-Insomnia
-Acne
increased appetite

Tacrolimus (FK506) and Cyclosporine (Calcineurin inhibitors) Mechanism of action

Inhibit T cell activity through inhibition of IL-2 production
Has crummy bioavailability and variable half life

Therapeutic range of Tacrolimus (FK506)

-5 to 15ng/mL

Tacrolimus interactions

Ketoconazole, diltiazem,
Phenytoin, rifampn
P glycoprotein substrate
Antacids

Cyclosporine Therapeutic Range

-50 to 200ng/mL

Cyclosporine drug interactions

Ketoconazole, diltiazem
Phenytoin, rifampin
P glycoprotein
Food (keep it consistent)

Tacrolimus monitoring

-Trough levels

Cyclosporine monitoring

- Trough levels | - C2 levels

Calcineurin Inhibitors adverse effects

- More severe with Tacrolimus than cyclosporine - Nephrotoxicity - Hyperglycemia - HTN - Electrolyte abnormalities

Mycophenolate

- Antiproliferative - Prodrug of mycophenolic acid (MPA) - Prevents T and B lymphocytes proliferation

Mycophenolate in pregnancy

- NO - Must have negative pregnancy test prior to starting - Use two methods of contraception

Azathioprine

- Antiproliferative - Prodrug of 6MP - Prevents T and B cell proliferation - Only used in patients who are intolerant to mycophenolate

Azathioprine Drug interactions

- 6MP | - Allopurinol

Sirolimus

- mTOR inhibitor | - Suppresses cytokine mediated T cell proliferation

Everolimus

- mTOR inhibitor - Suppresses cytokine mediated T cell proliferation - Used in renal transplant rejection prophylaxis

Belatacept

- Binds to CD80 and 86 on APCs blocking stimulation of T cells - Used for maintenance immunosuppression in renal transplant recipients

Adverse effects of Belatacept

``` -Post transplant lymphoproliferative disorder ^Black box warning -GI -HTN -Edema ```

Immunosuppression considerations

- Rejection - Toxicity - Adverse effects - Infection - Cost - Interactions - Cancer

Cardiovascular Complications

- Leading cause of mortality in renal transplant recipients - HTN - Hyperlipidemia - Diabetes

Infectious Complications

- Highest risk immediately following transplant and rejection treatment - Atypical organisms - Opportunistic infections - Prophylaxis

Malignancy Complications

- Related to degree of immunosuppression - Increased risk of lymphomas and lymphoproliferative disorders - Renal, skin, and Kaposi's sarcoma

Sensitization and Risk Factors for Rejection

a) Sensitization - Previous pregnancy - Blood transfusion - Previous transplant - HLA mismatch b) Risk factors - Delayed graft function - Rejection episodes - African american

Barriers to adherence

- System - Motivation - Understanding - Recall - Financial