Renal Transplant Flashcards
benefits of transplant
longer survival
health care cost savings
improved quality of life
not life saving - renal replacement therapy
3 things considered for kidney allocation
medical need
utility
justice
types of living kidney donors
direct donation
kidney paired exchange
altruistic
types of decreased kidney donors
neurological determination death
donation after cardiac death
medical assistance in dying
who are highly sensitized kidney transplant recipients
PRA >95%
what are human leukocyte antigens
markers on most cells that identify self from foreign
match between A, B, DR, DQ types
degree of HLA difference = ______________
degree of immunologic risk
what are some sensitizing events that can lead to antiHLA antibody
pregnancy
blood transfusions
previous transplant
what is panel reactive antibody screening
degree of transplatability
ex 95% incompatible for transplant with 95 out of 100 potential donors
what is cross matching, whats a positive result
a test between donor and recipient
positive is bad means the recipients cells can recognize and attack donor cells, increased risk of rejection
what is a common cause of someone developing antibodies to the donor after the transplant
often result of non compliance
what is used in induction therapy
intense immunosuppressive therapy at time of transplant to reduce risk of acute rejection
- deplete antibodies with thymoglobulin
- non depleteing antibodies : basiliximab
- corticosteroids: prednisone
ex calcineurin inhibitors
cyclosporine
tacrolimus
ex corticosteroids
prednisone
methylprednisilone
ex antiproliferatives
azathioprine
mycopehnolate
ex rapamycins
sirolimus
what is the standard therapy for adult kidney transplant
tacrolimus: inhibits early in tcell activation
mycopehnolate mofetil: decrease t cell proliferation
prednisone: inhibits lymphocytes
calcineurin inhibitor AE
increase BG - TAC increase BP, K, uric acid increase lipids (CSA) decrease Mg, P tremor nephro and hepato toxicity gingival hyperplasia hair growth CSA hair loss TAC
calcineurin inhibitor are substrates and inhibitors for
cyp3A4 and pgp
CSA > inhibitor
what can cause loss of pgp
diarrhea can cause sloughing of intestinal endothelium
inhibitors of cyp 3A4 that increase CSA and TAC
azoles macrolides non DHP CCB grapefruit juice protease inhibitors
inducers of cyp 3A4 that increase CSA and TAC
rifampin phenytoin carbamazepine phenobarbital stjohns wort
minoxidil + csa
hirsutism
phenytoin, nifedipine + CSA
gum hyperplasia
statins, dig , capsofungin _ CSA
decreased clearance
colchicine + CSA
increased myopathy and hepatotoxicity
glyburide + CSA
increase CSA level
repaglinide + CSA
increased repaglinide exposure
warfarin + CSA
decrease INR and CSA levels
potassium sparing diuretics + CSA
hyperkalemia
which statins might be ok to use with CSA
pravastatin and fluvastatin
tecrolimus DI
potassium sparing diuretics cause hyperkalemia
metoclopramide increase tacrolimus - not a worry
statins - atorv low dose ok
NOACs and CI
dabigatran not recommended
rivaroxiban unknown
apixaban likely safe
which drugs have additive nephrotoxicity with CI
nsaids ACei aminoglycosides amphotericin B renal sparin = CCB
sirolimusAE
increased lipids, proteinuria, delayed wound healing, anemia, hypertension
caution in liver and lung transplant - hepatic artery stenosis, bronchial anastomotic dehiscence
spacing of cyclosporin and sirolimus
give CSA 4 hours before or will get increase concentrations of sirolimus
sirolimus DI
cyp 3A4 substrate
same as CI
azathioprine AE
bone marrow suppression
hepatotoxicity
use TPMT phenotype to guide dosin (enzymes that metabolizes azathioprine)
mycopehnolate AE
leukopenia
GI intolerance
azathioprine DI
allopurinol - increase AZA
ACEi - increased neutropenia
warfarin - decreased INR
mycophenolate DI
antibiotics - may change enterohepatic recirculation
cholestyramine - prevents reabsorption via enterohepatic recirculation
PPIs - decreases myco levels
antacids - separate by 2 hours
iron preps
prednisone AE
increase lipids, BG, BP sleep disturbance increased appetite and weight mood swings, osteoporosis acne fluid retention
general drugs to avoid
immmune stimulants duh
decongestants - increase BP
PPIs - use lowest dose
NSAIDs, aminoglycosides, amphotericin B
blood concentration must correlate with
exposure
clinical outcomes - therapeutic and toxic
trough level within 30 min pre dose target CSA
50-150mcg/L
depends on time since transplant and individual patient
trough level target in tacrolimus
correlated well with AUC
6-8mcg/L
sirolimus trough level target
correlates well with drug exposure
6-10mcg/L depends on time since transplant and patient
mycophenolate trough level targets
wide individual variability
no time point accurately reflects exposure
dont measure levels
what else do you want to know if get dyslipidemia on therapy
BMI diet and exercise smoking CVD history renal function
effects of statins and immunisuppressants
lipids and CV disease is common
myopathy with CSA
increased statin exposure
atorva, prava, fluva, simv safe at lose dose esp tacrolimus
what do you recommend for dyslipidemia after transpalnt
diet exercise
smoking cessation
start low dose statin and monitor for side effects
fibrates?
no outcome data
ezetimibe?
no data in renal transplant
resin?
drug binding, absorption interference
niacin?
glucose issues
increased uric acid
fish oil?
no benefit but not harmful
how long do we prophylactically treat pcp
3 months
co-trimoxazole
treatment for pcp
septrafor 3 weeks
when and what prophylaxis do you give for cmv
give valganciclovir for 6 months in people with mismatched CMV status to their donor or with use of induction agents
(donor +, and recipient - biggest risk)
pre emptive treatment for cmv
routine screening using PCR
treatment until 2 negative PCR
treatment of cmv in invasive tissue disease
severe leukopenia can occur
ganciclovir IV, valganciclovir po
why is routine screen screening for BK viraemia and graft dysfunction important
BK virus common in general pop may be reactivated in immunosuppressed state leading to nephropathy and graft failure
treatment of BK virus
no good treatment
reduce baseline immunosuppression
switch to cyclosporin
EBV is associated with devellpment of post transplant lymphoproliferative disorder when should routine screening occur
if EBV mismatch at time of transplant
treatment for EBV
lower immunosuppressive therapy
most common infection post transplant
UTI
complications of pyelonephritis
sepsis
graft dysfunction and failure
UTI prophylaxis
in first 3 months TMPSMX
vaccines in renal transplant
avoid live
can get flu shot after 3 months and vaccines after 6
the “ABCDEs” we should know
anemia - lots of blood work, takes time for kidney to start epo production analgesia bone density - decrease due to steroids and renal bone disease blood pressure - increase cholesterol - increase cancer risk BG - increased depression - steroid use eyes- cataracts from steroids exercise
mycophenolate and fertility
teratogenic in females
unknown for sure effects in males
switch to azathioprine if planning for pregnancy, wait at least 1 year post transplant
goals of transplant
prolong graft survival
prevent rejection episodes
min long term complication s
