Renal transplant Flashcards
(10 cards)
Name 5 causes of acute allograft dysfunction
Volume depletion
Mechanical (renal artery or vein, ureteric obstruction, lymphocele)
HUS/TTP
Rejection
ATN
Pharmacology (CNI, interstitial nephritis)
Infection (CMV, BK virus)
What is the mechanism of cyclosporin (CsA)?
Competitive binding to and inhibition of calcineurin (a Ca++ dependent phosphatase)
(And for brownie points…)
This inhibits translocation of a family of transcription factors, NF-AT, reducing transcriptional activation of early CK genes for IL-2,3,4, CD40L, TNFa, IFNy
What are 3 adverse effects of cyclosporin
Nephrotoxicity - Acute: vasospastic, HT - Chronic: striped fibrosis Thrombotic microangiopathy/HUS DM Metabolic (K, urate, low Mg) Neurotoxicity (especially tremor) Hirsutism Gingival hyperplasia
What is the mechanism of Tacrolimus (FK506)?
Blocks action of calcineurin in activated T cells. Target is FKBP-12.
What is the mechanism of mycophenolate mofetil / sodium?
Converted to mycophenolic acid, which selectively suppresses lymphocyte proliferation and antibody formation by inhibiting inosine monophosphate dehydrogenase (IMPDH).
Acts on the immune system at a similar level to azathioprine but by a distinct and more lymphocyte-selective mode of action.
What are two adverse effects of mycophenolate?
GI (diarrhoea)
Myelosuppression
What are 2 side effects of Tacrolimus?
Alopecia (common)
Cardiomyopathy
What is the drug interaction between CsA and MMF?
CsA lowers MMF levels
What is the mechanism of mTOR inhibitors?
Bind to the same intracellular protein (FKBP‑12) as tacrolimus; however, the protein-drug complex blocks the activity of mTOR kinase, preventing cell cycle progression and cytokine-induced T and B cell proliferation.
What are 3 side effects of mTOR inhibitors?
Infections Oedema Leucopenia/thrombocytopaenia/anaemia VTE HUS/TTP Hyperglycaemia/cholesterol/triglyceridaemia Impaired wound healing Mouth ulcers Sirolimus pneumonitis - dose related, responds to cessation +/- steroids Male infertility (reversible)
