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Dr. Zhang's Transplant
Anti-body-ody-ody
Transplant
PT Backbone
100

Most common solid organ transplantation

kidney transplantation

100

ATG vs RATG

Equine vs Rabbit (les immunogenic)

100

Given to HIGH Immunologic Risk Patients (Drug, premeditants, route)

ATG Rabbit Thymoglobulin with Methylprenisolone, APAP, and Diphenhydramine 30-60 minutes prior.

Prefer Central line. Heparin and Hydrocortisone needed.

100

Calcineurin Inhibitors

Tacrolimus: 

IV:PO = 1:4

PO:SL = 2:1

IR-TAC: LCP-TAC = 1:0.8 TDD

IR-TAC: ER-TAC = 1:1 TDD


Cyclosporine: IV: PO = 1:3

200

4 Classifications of Rejection

Hyperacute Rejection: Donor-specific antibodies are present in recipient

Acute Cellular rejection: appear in the circulation and infiltrate the allograft

Antibody-mediated rejection: Vascular/Humoral Rejection characterized by antibodies against donor's HLA antigens 

Chronic Rejection: Cell and/or antibody-mediated rejection. Major cause of graft loss

200

Non-depleting Antibodies

Basiliximab (IL-1 receptor antagonist) - prevents IL-2 mediated activation and proliferation of T cells

200

Give Basiliximab

LOW immunologic risk

HIGH risk for infection

Renal dysfunction requiring CNI

200

Mycophenolic Acid

Mycophenolate

IV:PO = 1:1

250 mg MMF = 180 mg EC-MPA

Azathioprine

300

Pathophysiology of Rejection

  1. Recognition of the donor’s histocompatibility differences

  2. Recruitment of activated lymphocytes

  3. Initiation of immune effector mechanisms

  4. Graft destruction

300

MOA of Myophenolate Mofetil

Decreased  Nucleotide Synthesis --> reduces lymphocyte proliferation

300

High risk for Rejection (5)

  1. Previous transplant

  2. High PRA (Panel-reactive antibody)

  3. Positive DSA (Donor-specific alloantibody)

  4. Positive HLA crossmatch (Human Leukocyte Antigen)

  5. African-American

300
Unique for Azathioprine

Test for TPMT activity!

400

Improves Immediate, in Days, in Weeks

Immediately: GFR

Days: Scr, BUN

Weeks: Anemia, Ca/Ph imbalance, ALP

400

Binds to FKBP-12 and inhibits Calcineurins

Binds to FKBP-12 and inhibits MTOR

Binds to Cyclophilins and inhibits Calcineurins

Binds to Cyclophilins and inhibits Calcineurins - Cyclosporine

Binds to FKBP-12 and inhibits Calcineurins - Tacrolimus

Binds to FKBP-12 and inhibits MTOR - Sirolimus

400

Short term & long-term adrs of Corticosteroid usage

Short-term: increased Blood Pressure & Glucose, Fluid Retention, increased appetite, Insomnia

Long-term: HTN, DM, DLD, Moon Face, osteoporosis, Cataracts,

400

Corticosteroids

4 mg IV methylprednisolone = 5 mg PO prednisone

500

Activation of T-cells

  1. Requires MHC II molecule complex recognized by teh T-cell recognition complex (TCR)

  2. Costimulatory signal initiates signal transduction

  3. Activation of Calcineurin and Dephosphorylation of NFAT

  4. NFAT facilitates IL-2 gene transcription

  5. IL-2 activates IL-2 receptor

  6. IL-2 receptor signaling pathway

  7. T cell proliferation and production of cytokines specific to the T cell

500

Depleting antibodies: which hits T, which hits B, which hits both

ATG & RATG: T cells and Lymphocytes

Rituximab: B cells

Alemtuzumab: T and B lymphocytes

500

Given to prevent Opportunistic Infections:

Cytomegalovirus (CMV):

Pneumonia (PJP):

Aspergillus:

Thrush:

Cytomegalovirus (CMV): Ganiciclovir, Valganciclovir, letermovir

Pneumonia (PJP): Sulfamethoxazole-trimethoprim (Bactrim), Dapsone, Atovaquone, Pentamidine

Aspergillus: Posaconazole Preferred, Voriconazole, Isavuconazole.

Thrush: Fluconazole, Clotrimazole, Nystatin

500

Others:

Rapamycin Inhibitors: Sirolimus, Everolimus

Co-stimulation Inhibitors: Belatacept. CI in EBV IgG negative patients