Most common solid organ transplantation
kidney transplantation
ATG vs RATG
Equine vs Rabbit (les immunogenic)
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.
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
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
Non-depleting Antibodies
Basiliximab (IL-1 receptor antagonist) - prevents IL-2 mediated activation and proliferation of T cells
Give Basiliximab
LOW immunologic risk
HIGH risk for infection
Renal dysfunction requiring CNI
Mycophenolic Acid
Mycophenolate
IV:PO = 1:1
250 mg MMF = 180 mg EC-MPA
Azathioprine
Pathophysiology of Rejection
Recognition of the donor’s histocompatibility differences
Recruitment of activated lymphocytes
Initiation of immune effector mechanisms
Graft destruction
MOA of Myophenolate Mofetil
Decreased Nucleotide Synthesis --> reduces lymphocyte proliferation
High risk for Rejection (5)
Previous transplant
High PRA (Panel-reactive antibody)
Positive DSA (Donor-specific alloantibody)
Positive HLA crossmatch (Human Leukocyte Antigen)
African-American
Test for TPMT activity!
Improves Immediate, in Days, in Weeks
Immediately: GFR
Days: Scr, BUN
Weeks: Anemia, Ca/Ph imbalance, ALP
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
Short term & long-term adrs of Corticosteroid usage
Long-term: HTN, DM, DLD, Moon Face, osteoporosis, Cataracts,
Corticosteroids
4 mg IV methylprednisolone = 5 mg PO prednisone
Activation of T-cells
Requires MHC II molecule complex recognized by teh T-cell recognition complex (TCR)
Costimulatory signal initiates signal transduction
Activation of Calcineurin and Dephosphorylation of NFAT
NFAT facilitates IL-2 gene transcription
IL-2 activates IL-2 receptor
IL-2 receptor signaling pathway
T cell proliferation and production of cytokines specific to the T cell
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
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
Others:
Rapamycin Inhibitors: Sirolimus, Everolimus
Co-stimulation Inhibitors: Belatacept. CI in EBV IgG negative patients