Transplant Flashcards
Most common transplant organ?
kidney
What is a autograft?
from self ie skin graft
What is allograft/
from same speciesq
What is a xenograft?
different species
What is isograft?
from twin
Why can you get less immunosuppression for liver transplants?
can regain so better at transplanting
What organ needs ALOT of immunosuppression?
lung
What is MHC/ HLA? Where are they found?
distinguishes self from non self
on antigen presenting cells (B cell, macrophage
What do APC’s do?
present antigen to T cells
What do CD4 or t helper cells do?
recog MHC class2 and stims B cells and t cells
What do CD8 or cytotoxic T cells do?
recog MHC class 1 and kill infected cells
What do B cells do?
forms antibodies
What do histocompatibility antigens do?
bind peptides and present them on cell surface for inspection of t cells
Why do we match HLA and not MHC?
HLA is more specific for human
What chromosome is HLA on?
Chromosome 6
What cells have HLA class 1?
most cells and platlets
What cells have class 2?
immune cells
What cells have class 3?
don’t worry no role in grafts
What is inheriting from haplotype mean? What’s the odds of being the same?
HLA genes are given as a group
1/4 siblings have the same
If perfect HLA match is there still a chance of rejection?
yes
What does signal 1 do?
recognition of MCH 2 and begin activation calcineurin pathway to make IL-2
What does signal 2 do?
Acitvate T cells by timing CD80 and 86 and 28
What does signal 3 do?
IL-2 released and binds on T cell for proliferation
Why are the signals of T cell an important target?
causes graft destruction
and activates calcineurin which is targeted
Do B cells play a role in matching?
yes by creating donor specific antibodies (DSA)
if due to this called humeral rejection
What is a PRA?
cross match blood sample with donors to see how much HLA antigens are present
What does a high PRA percentage mean?
bad because there is broad sensitization
Con of PRA?
doesn’t know strength of reaction
What is a lymphocyte cross match test mean?
directly tests reactivity between patient and donor cells if positive= BAD
What is the importance of ABO blood matching?
stops hyper acute reaction and destruction of the graft
Treatment of chronic rejection?
none hope immunosuppressants stop the beginning of process
What causes acute cellular rejection? When does this occur?
by t lymphocytes
can happen anytime
How long does induction therapy last?
1-3 months
What drugs must be given for induction?
Basiliximab OR Antithymocyte globulin
AND
corticosteroid
AND
Azathiprine OR Mycophenolate
AND
cyclosporine OR tacrolimus
How does basiliximab work?
Il-2 receptor antagonist
S/e of basiliximab?
hypersensitivity but VERY well tolerated
General dosing info on basiliximab?
everyone gets same dose
How does anti-thymocyte globulin work?
this antibody binds to T cells and depletes them
Main difference between basiliximab and antithymocyte?
Antithymocyet is a polyclonal antibody so binds more
S/e of antithymocyte?
bone marrow suppression, anaphylaxis, hepatic issues
Which agent can be used if rejection is happening?
antithymocyte
Short term s/e of corticosteroids and long term?
Short= insomnia, Gi, glucose, poor wound healing
long= osteoporosis, cataracts, moon face
Does CS cause hypo or hyper kalmia?
hypokalemia
How can we prevent osteoporosis?
routine bone tests, calcium, vitamin D, bisphosphonates
What other agent besides CS causes hyperglycaemia?
tacrolimus
MOA of azathioprine?
purine analoge that suppresses T and. B cells
Main DI with azathioprine?
allopurinol- people often get gout
CAUSES MYELIN SUPPRESSION
S/e of azathiprine?
alopecia, bone marrow suppression, skin lesion
MOA of mychophenolic acid derivatives?
more specific ability than AZA to suppress B cells and T cells
General dosing of MPA?
everyone gets the same dose
Do you need blood tests for MPA?
NO
S/e of MPA?
Gi is bad, neutropenia
teratogen for both males and females
DI of MPA?
iron and calcium and other agents that cause neutropenia
Can you give MPA with food?
yes to help with Gi just slows absorption NOT extent
is it a good idea to divide doses of MPA foo help with gi?
helps but lowers adherence
What agent causes bad neutropenia with MPA?
Valganciclovir
If neutropenia happens with MPA what can we do?
filgrastim/GCSF to cause WBC proliferation
How do cyclosporin and tacrolimus work?
binds calcineurin which stops T cell activation
What is important about dosing with cyclosporin and tacrolimus?
narrow TI which is gets serum levels right
What metabolizes cyclosporin/ tacrolimus?
CYP 34A
How does the neural formulation of cyclosporin improve the drug?
less variable and improved BA
How do you do blood levels of cyclosporin? Which method is better?
trough or 2 hour post dose
2 hours post is better for AUC but must be within 15 minutes of the 2 hours
True or false Advagraf and prograf are bio equivalent?
FALSE prograf is BID and advagraft is ER
How do you do blood levels of tacrolimus?
trough needs to be within 30 minutes of C0
S/e of the calcineurin inhibitors?
nephrotoxicity, neurotoxicity- headache, fatigue
electrolytes issues (K increase)
gi
hepatic
Which calcineurin inhibitors has worse gi?
tacrolimus, especially with MPA
Unique s/e of tacrolimus?
alopecia
unique s/e of cyclosporin?
more limipds and uricemia, acne, facial hair, gingival hyperplasia
How to help with lipid s/e of cyclosporin?
statin BUT lowest dose due to DI causing more muscle pain
DI with calcineurin inhibitors?
macrolide (NOT azithro), diltiazem, verapamil, fluconazole, grapfruit, other nephrotoxic agents
MOA of sirolimus?
Macrolide antibiotic similar to tacrolimus that binds to FKBP and engages TOR which lowers proliferation
Important PK info of sirolimus?
LOOOOONG half life (60 hours)
same DI as tacrolimus
When would we use sirolimus?
to replace calcineurin agents due to low renal function, anti malignancy properties, add on
S/e of sirolimus?
BAD hyper lipids, rash, mouth sores, edema, proteinuria, anemia
What side effect must you stop siroliimus?
proteinuria
Patient comes in complaining of edema and is on sirolimus. What agent can we give?
DIURETICS DO NOT WORK
How to treat acute rejection?
HIGH dose CS
antithymocyte
How to treat humeral rejection?
plasmapheresis (dialysis for antibodies), CS, antithymocyte, rituximab, tocilzumab, bortezomib
How frequent is blood work for transplant patients?
minimum monthly forever
How frequent is blood work for heart transplants?
prob q3 months due to no good biomarkers if stable
Which drugs need level monitoring?
CNI, Sirolimus
Should we use generic immunosuppressants?
Cheaper so yeah but LOTS more monitoring when switching so patient must be made aware
Who is eligible for kidney transplant?
when GFR under 20
What other transplant is common with kidney?
pancreas
Signs of acute and chronic kidney rejection?
acute= abrupt >30% increase in SCr, low urine production, pain by kidney
Chronic= HTN, proteinuria and low renal function
When do we need delayed graft function? and why?
if no pee after transplant need dialysis to kickstart kidney
What is a common opportunistic infection with kidney grafts?
BK virus/polyoma virus due to so high immunosuppression
Who is eligible for liver transplant? And what conditions are common?
advanced, nonreversible decompensated liver disease
causes= Hep C+B, PBC,PSC, alcohol
How is immunosuppression different in Liver grafts?
can eventually taper off CS first then MPA after a year
Signs of acute and chronic liver rejection?
Acute= increase in enzymes and bilirubin
chronic= LFTs, jaundice and itching
What conditions can cause recurrent disease in liver?
Hep B and c, PBC and PSC
Who is eligible for heart transplant?
advanced heart failure, non responsive to therapy, otherwise HEALTHY, but survival about 1 year
How is immunosuppression different in heart grafts?
prednisone is eventually tapered off
Issues with heart grafts?
higher resting rate, can’t tolerate exercise, MI can be asymptomatic
If heart transplant what meds MUST be on board?
statin, ASA, ACE
Signs of acute and chronic rejection of heart grafts?
Acute= mostly asymptomatic, heart failure sx
chronic= vasculopathy (plaque in grafted vessels
Who is eligible of lung transplants?
HEALTHY,YOUNGER, end stage and failing max therapy, able to adhere
Difference in immunosuppression in lung grafts?
possibly quad therapy
signs of chronic rejection of lung graft?
CLAD- happens a lot after 5 years give azithro
What is CMV and what is therapy?
most common virus and risk is highest with D+R-
give valganciclovir and screening with CMV PCR
What is PJP prophylaxis?
SMX-TMP perhaps always if lung
sulpha allergy give dapsone or inhaled pentamadine
What can we do for herpes simplex reactivation?
valganciclovir some help but usually therapy
Why is Epstein Barr virus so bad?
can cause PTLD which is cancer and need prophylaxis and monitoring if D+R-
How can we minimize malignancy risk?
sunscreen, pap and colonoscopy, term exams
Who is most at risk of PTLD?
kids
How do we treat PTLD?
lower immunosuppression or rituximab
If bad gi issues on meds what can we do?
PPI
What is blood pressure target for graft patients?
Lower is better but as tolerated
Which is worse for renal grafts, ACE or diuretics?
diuretics
Is CCB good for BP in graft patients?
use amlodipine but worse peripheral edema, gingival hyperplasia
What can we do if anemia?
EPO dugh
What drug is worse for gout in transplant therapy?
Cyclosporin
What is paired exchange and altruistic donor?
Paired= if want to donate but no match go on registry for later
altruistic= stagner donating
