Term
improves morbidity and mortality
option when other medical treatments are inadequate
improve quality of life |
|
Definition
| rationale for transplantation |
|
|
Term
kidney
heart
lung
liver
small bowel
pancreas
heart/lung
kidney/pancreas
cornea
bone
skin |
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Definition
|
|
Term
kidney: old kidney left in place, new kidney placed in the right iliac fossa; donor ureter, renal artery and vein are also transplanted
liver: old liver must be removed, then new liver transplanted
heart: recipient's major vessels left in place and are attached to new heart
pancreas: recipient pancreas remains intact; part of donor duodenum transplanted with pancreas |
|
Definition
| surgical process of a kidney, liver, heart, and pancreas transplant |
|
|
Term
|
Definition
bone marrow derived lymphocytes
encounter antigen to which their surface immunoglobulin has specificity
APC function
activate CD4+ T-cells
differentiate into plasma cells and memory cells |
|
|
Term
|
Definition
MOST IMPORTANT CELLS IN ALLOGRAFT REJECTION
activity largely mediated by IL-2
encounter APCs presenting specific antigen (DO NOT recognize antigen alone)
thymus derived lymphocytes |
|
|
Term
MHC I: HLA-A and HLA-B
HHC II: HLA-DR |
|
Definition
| the most important subclasses of MHC I and MHC II in terms of transplants |
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|
Term
HLA matching:
testing MHC I (subtypes HLA-A and HLA-B) and MHC II (subtypes HLA-DR)
minor HLA not used for matching but may lead to rejection -> reason that non-identical individuals require immunosuppression
HLA matching increases "cold ischemia" time
primarily done in kidney transplants; not routinely done with other organs
blood type matching is required for all transplants
panel reactive antibodies (PRA):
a panel of common random antibodies
recipients are tested for reactivity
if they have > 10-20% reactivity, HLA typing must be done for that recipient |
|
Definition
| matching that is required for transplants |
|
|
Term
pregnancy
previous transplant(s)
multiple blood transfusions |
|
Definition
| risks of elevated panel reactive antibodies |
|
|
Term
|
Definition
preformed donor antibodies present: complement fixing antibody (blood ABO and/or MHC antigens) bind to vascular epithelium
occurs within 48 hours
no known treatment
incidence <1% |
|
|
Term
|
Definition
T-lymphocyte mediated: CD8 and CD4 cells involved
delayed type hypersensitivity reaction
usually occurs within first 90 days, but may occur anytime
biopsy is done to confirm
PREVENTION IS MAIN GOAL OF IMMUNOSUPPRESSIVE THERAPY
reasons: failure of regimen, non-adherence |
|
|
Term
fever
increased SrCr
hypertension
edema
weight gain |
|
Definition
| symptoms of acute kidney rejection |
|
|
Term
fever
leukocytosis
change in bile color/consistency
increased LFTs/bilirubin |
|
Definition
| symptoms of acute liver rejection |
|
|
Term
asymptomatic early
fever
malaise
heart failure |
|
Definition
| symptoms of acute heart rejection |
|
|
Term
|
Definition
rejection that occurs > 90 days after transplant: slow, indolent pathologic changes
immunologic and non-immunologic:
immunologic = humoral role
non-immunologic = drug toxicity, comorbidities, donor disease, infectious disease
ultimately results in obliterative disease via allograft fibrosis
no known effective therapy
change from calcineurin inhibitors to sirolimus of MMF may help prevent further damage
treat comorbid diseases to prevent further damage |
|
|
Term
previous transplant(s)
acute tubular necrosis
African-American
pancreas, lung, or small bowel transplant
high PRA titer
poor match
cadaveric donor |
|
Definition
| patients with high immunological risk of rejection |
|
|
Term
primary transplant
Caucasian
living transplant
low PRA titer |
|
Definition
| patients with low immunologic risk of rejection |
|
|
Term
|
Definition
| length of immunosuppressive therapy for transplant patients |
|
|
Term
all patients get perioperative high dose IV steroids (dexamethasone or methylprednisolone)
high risk patients also receive aggressive immunosuppressants
therapies are started intraoperatively or immediately post-op
calcineurin inhibitors are typically not used in induction
therapies target IL-2 or T-cells |
|
Definition
|
|
Term
Basliliximab and Daclizumab: target IL-2 receptor
ATG, thymoglobulin, and muromonab: anti T-cell antibodies
corticosteroids: interfere with macrophage function, inhibit synthesis and release of IL-1, inhibit IL-2 secretion from T-cells, nonspecific anti-inflammatory effects |
|
Definition
|
|
Term
agents:
thymoglobulin and ATG - polyclonal antibodies
place in therapy:
induction
reverse steroid-resistant acute rejection
MOA:
bind to activated T-cells (multiple sites)
may alter ability of T-cells to cause rejection
cause profound depletion of population
MUST BE GIVEN VIA A CENTRAL LINE |
|
Definition
antithymocyte globulin:
agents and place in therapy and MOA |
|
|
Term
place in therapy:
induction
reverse steroid-resistant acute rejection
MOA:
monoclonal antibody
potent anti T-cell immunosuppressant
targets mature T-cells expressing CD3 antigen in T-cell receptors
monitoring:
CD3% (goal <5%)
human antimurine antibody (HAMA) titers - limits the ability for reuse |
|
Definition
Muromonab:
place in therapy and MOA and monitoring |
|
|
Term
MOA:
targets IL-2 receptor CD25 - low on resting T cells and is induced on activated T cells
basiliximab is chimeric (xi)
daclizumab is humanized (zu)
place in therapy:
induction only |
|
Definition
basiliximab and daclizumab:
MOA, place in therapy |
|
|
Term
flu-like symptoms
rigors
myelosuppression |
|
Definition
|
|
Term
flu-like symptoms
rigors
myelosuppression |
|
Definition
| common ADRs of thymoglobulin |
|
|
Term
flu-like symptoms
pulmonary edema |
|
Definition
|
|
Term
|
Definition
| common ADRs of diclizumab |
|
|
Term
calcineurin inhibitors: cyclosporin, tacrolimus
antiproliferatives: azathioprine, mycophenolate
mTOR inhibitors: sirolimus
corticosteroids
calcineurin inhibitors are backbone of therapy
adjunctive therapy with sirolimus or mycophenolate
steroid avoidance is a major goal |
|
Definition
| agents used for maintenance therapy |
|
|
Term
agents:
cyclosporin and tacrolimus
MOA:
inhibit calcineurin inhibiting transcription of IL-2 early in the T-cell activation pathway
monitoring:
drug levels have to be monitored
trough levels must be drawn PRIOR TO AM dose
drug interactions:
CYP3A4
drugs that cause nephrotoxicity (aminoglycosides, furosemide) |
|
Definition
calcineurin inhibitors:
agents, MOA, monitoring, drug interactions |
|
|
Term
neoral and gengraf are interchangeable
sandimmune and neoral/gengraf are NOT interchangeable |
|
Definition
are sandimmune, neoral, and gengraf interchangeable?
forms of cyclosporin |
|
|
Term
cyclosporin:
MORE ADRs associated with HTN and hyperlipidemia
same with renal ADRs
tacrolimus:
MORE ADRs associated with GI, endocrine (hyperglycemia), and CNS |
|
Definition
| comparison of ADRs between cyclosporin and tacrolimus |
|
|
Term
agents:
azathioprine and mycophenolate
Place in therapy:
maintenance
considered adjunctive therapy
MOA:
metabolized to 6-mercaptopurine in vivo
6-MP inhibits DNA and RNA synthesis by preventing the formation of adenylic and guanylic acids from inosinic acid
interferes with proliferation of T and B cells
dose adjustments:
adjust dose based on CBC
reduce dose in renal impairment
reduce dose in combination with allopurinol
ADR:
bone marrow suppression |
|
Definition
antiproliferatives:
agents, place in therapy, MOA, dose adjustments, ADR |
|
|
Term
agent:
sirolimus
MOA:
suppresses cellular response to IL-2, IL-4, and IL-15
binds to FK binding protein
interferes with the signaling of IL-2
markedly suppresses T-cell proliferation
toxicities:
hyperlipidemia - especially TGs
place in therapy:
maintenance
may decrease CMV disease
useful in calcineurin free regimens
may decrease risk of malignancy |
|
Definition
mTOR inhibitors:
agent, MOA, toxicities, place in therapy |
|
|
Term
nephrotoxicity
increased cholesterol
HTN |
|
Definition
| common ADRs of cyclosporin |
|
|
Term
nephrotoxicity
GI upset
glucose intolerance
neurotoxicity |
|
Definition
| common ADRs of tacrolimus |
|
|
Term
myelosuppression
GI upset
hepatoxicity
pancreatitis |
|
Definition
| common ADRs of azathioprine |
|
|
Term
|
Definition
| common ADRs of mycophenolate |
|
|
Term
myelosuppression
increased cholesterol
mouth sores |
|
Definition
|
|
Term
|
Definition
| common ADRs of prednisone |
|
|
Term
each episode of acute rejection shortens the overall life of the graft
high doses of steroid initiated and subsequently tapered when rejection has resolved
anti leukocyte antibodies used when steroids aren't enough
after rejection:
increase maintenance dose of meds (especially calcineurin inhibitors)
add another immunosuppressant (different class from other meds) |
|
Definition
|
|
Term
risk of rejection
infection
risk of ulcers
CV complications
malignancy |
|
Definition
|
|
Term
bacterial: wound, catheter-related, pulmonary, UTI
fungal: candida, aspergillus
Viral: CMV, HSV, EBV, BKV
protozoan: PCP, toxoplasmosis |
|
Definition
| common infection associated with transplants |
|
|
Term
risk mainly due to corticosteroids
consider if patient in ICU, surgical complications, protracted hospital course
usually given to patients on > 10mg of prednisone daily |
|
Definition
| when is GI prophylaxis given to patients to prevent ulcers? |
|
|
Term
cardiovascular death is leading cause of death after 1 year (less than one year is infection)
HTN
post-transplant DM
hyperlipidemia (calcineurin inhibitors, sirolimus)
CKD |
|
Definition
| CV complication associated with transplants |
|
|
Term
Kaposi's sarcoma
squamous cell carcinoma
non-Hodgkin's lymphoma
skin cancer
cancer of vulva and perineum
post-transplant lymphoproliferative disorder |
|
Definition
| transplant patients are at an increased risk of what malignancies? |
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