Steroids + Drugs | Mechanisms of action | Pros | Cons |
Tacrolimus (TAC) | *Binds FKBP12 and inhibits calcineurin dephosphorylation of NFAT, a transcription factor (TF) for IL-2 synthesis. | *TAC/MMF/steroids most effective maintenance ISA *GC supports Tregs/ graft tolerance *GC inhibits TF: AP-1 and NFKB *Activate renal P-glycop/ cyt P450: reduce nephrotoxicity |
*TAC diminishes IL-2 support for AICC and graft tolerance *TAC/MMF/GC may promote BK virus infection *GC + TAC promote NODAT/ Hypertension/ hyperlipemia |
Cyclosporine (CsA) | *Binds cyclophillin and inhibits calcineurin dephosphorylation of NFAT, a TF for IL-2 synthesis. | *Similar to TAC but may be less effective | *Similar to TAC but more hyperlipemia and less NODAT *Increases serum MMF + toxicity |
Mycophenolate Mofetil (MMF) | *Inhibits IMDH + progression of cell cycle | *Allows lower doses of CNI/ GC *GC enhances UDPGT + decrease toxicity *GC attenuates BM depression |
*Bone marrow depression *CsA increases serum MMF + toxicity |
Sirolimus (SRL) | *Binds FKBP12 + mTOR to arrest growth cycle *Anti-proliferative agent |
*Reduces non-melanoma skin cancer *Survival of Tregs/ graft tolerance? |
*GC/RAP delay wound healing, cause NODAT + hyperlipemia *RAP delays graft function/ nephrotoxicity/ proteinuria *TAC/ RAP promote PTLD in EBV (-) / TMA |
Belatacept | CTLA4Ig: blocks co-stimulatory CD28 receptor | *Better short-term graft function vs. CsA *GC+Belatacept: Less CV morbidity vs. GC/CsA? |
*Promotes PTLD in EBV (-) *Does not inhibit memory T cell *More frequent early AR vs. CsA |