Renal Transplantation Flashcards
What are the benefits of renal transplantation?
- not life saving (like liver, lung or heart transplant)
- survival benefit
- improved QOL
- cost saving (after first year post transplant)
What are the advantages of a living donor vs a deceased donor?
- graft survival is longer (20 years minimum vs 13 years minimum)
- there is not as much of a wait time for a living donor
What are the types of living kidney donors?
- direct donation
- kidney paired exchange
- altruistic, non directed
What are the types of deceased kidney donors?
- neurological determination of death
- donation after cardiac death
- medical assistance in dying
What does a patient all have to go through as part of the recipient evaluation?
- tranplant nephrologist
- blood group, HLC typing, HLC cross matching, HLA antibody screening
- infection screening: TB, HBV, HCV, HIV, CMV, EBV, BK
- imaging: CXR, U/S
- cardiac evaluation
- vascular disease screen
- psychiatry assessment
(approx. 9 months in MB)
What is evaluated when matching donors to recipeints?
- HLA: human leukocyte antigens
- HLA are the markers on most cells that help to identify self from foreign
Class 1 HLA does what?
- stimulates T killer cells
Class 2 HLA does what?
- stimulates T helper cells, macrophages, B cells
Typical matching is between what?
- A, B, DR and DQ types
The degrees of ________ is directly related to the degree of immunologic risk?
- HLA disparity
- – the closer the match, the less immunosuppression that the person will have to have over time- the closest match a person will have will likely be their sibling
What sensitizing events can lead to an anti-HLA antibody?
- pregnancy, blood transfusions, previous transplant
- increased difficultly in finding a match in these cases
What is a PRA panel screening?
- this is the degree of transplantability
What is cross matching between a donor and a recipient?
- testing for HLA antibodies that can cause severe rejection and graft loss
- positive cross match here is bad - the recipients cells are able to recognize and attack the donor cells
- there is an increased risk of rejection
What happens when a person develops HLA antibodies after a transplant?
- there is an increased risk of graft loss in this case- often this is a result of non-conplaiance and under immunosuppression
How is immunosuppression achieved?
- depletion of lymphocytes, depletion of antibodies
- blocking of the lymphocyte response
(non-depleting monoclonal antibody IL-2 receptor antagonists, calcineurin inhibitors, antiproliferative agents, mTOR inhibitors)
What medications are used at the time of transplant to reduce the risk of acute injection- what is this referred to as?
- induction therapy
- can use wither DEPLETING ABS (anti-thrymocyte: thyroglobulin) or NONDEPLETING ABS (IL-2 receptor:basiliximab)
- also add on corticosteroids here- prednisone or methylprednisone
What drugs fall under the class of calcineurin inhibitors?
- cyclosporin
- tacrolimus
What drugs fall under the class of antiproliferatives?
- azathoprine
- mycophenolate mofetil
- mycophenolate sodium
What drug is considered to be a rapamycin derivative?
- sirolimus
What is the MOA of tacrolimus?
- inhibits earlt in T cell activation and clonal expansion
What is the MOA of mycophenolate mofetil?
- it works to decrease the T cell proliferation
What is the MOA of prednisone?
- sequesters and inhibits lymphocytes
Should use THREE drugs in combination for immunosuppression- what are they?
- T cell communication
- Antiproliferatives
- Prednisone
What are the T cell communication drugs? (calcineurin inhibitors)
- cyclosporine
- tacrolimus
What are the anti proliferative agents?
- azathioprine
- mycophenolate
- sirolimus
What is the calcineurin inhibitor that cause more diabetes?
tacrolimis
What CNI causes hair loss? Which one causes hair growth?
- hair loss: tacrolimis
- hair growth: cyclosporin
Diarrhea will cause an ____ drug level due to the pumping out of the drug
increased
What are the adverse drug reactions that come fro CNIs?
- increased blood glucose
- increased blood pressure
- increased lipids
- increased K
- decreased Mg
- decreased P
- increased UA
- tremor, nephro and hepatotoxicity, gingival hyperplasia
What CNI is a stronger inhibitor of cyp 3A4?
- CSA > TAC
What is the effect that a CNI will have on p-glycoprotein?
- both substrate and an inhibitor
- diarrhea can be caused by sloughing of intestinal endothelium -> loss of pgp -> increased CNI levels
- other medications may use the pgp pathway
What are some of the medications that will inhibit or increase the levels of CNIs?
- azoles
- macrolides
- non DHP CCBs
- grapefruit juice
- ritonovir/protease inhibitors
What are some of the medications that will induce or decrease the levels of CNIs?
- rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort
What is the effect from the interaction between cyclosporin and nifedipine/phenytoin?
- gum hyperplasia
What is the effect of the interaction between statins, dig and caspofungin?
- decreased clearance
What is the interaction between cyclosporine and colchicine?
- increased myopathy and hepatotoxicity
What is the interaction between warfarin and cyclosporin?
- decreased INR and CSA levels
What is the interaction between K sparing diuretics and cyclosporine?
- hyperkalemia
What are the 2 statins here that are okay to use with CSA?
- fluvastatin and pravastatin
What are the main drug interactions with tacrolimis?
- K sparing diuretics (cause hyperkalemia)
- metoclopramide (increased tacrolimis exposure)
- statins (TAC/atorvastatin might be okay)- but NEVER use atorvastatin 80
What is considered to be the “safer” NOAC to use with CNIs?
- apixaban- safer compared to warfarin
What drugs have additive nephrotoxicity when added onto cyclosporine and tacrolimus?
- NSAIDs, ACEI/ARB, aminoglycosides
What additive medication helps CNIs be renal sparing?
- CCBs - this is because they cause afferent vasodilation
What are the adverse DIs associated with sirolimus?
- increased lipids
- proteinuria
- delayed wound healing
- anemia
- hypertension
- caution in liver and lung transplant - hepatic artery stenosis, bronchial anastomotic dehiscence
What is a big drug interaction that is associated with sirolimus?
- cyclosporine: space CSA four hours before sirloins
- — if taken together will have increased sirloins concentrations
What are the medications that will increase SIR concentrations?
- azoles (single fluconazole dose has minimal effects)
- macrolides
- non DHP CCBs
- ritonavir/protease inhibitors
- grapefruit juice
What are the medications hat will decrease SIR concentrations?
- rifampin
- phenytoin
- carbamazepine
- phenobaribital
- St. John’s Wort
What drugs are considered to be anti-poliferative agents?
- azathioprine and mycophenolate
What are the AEs associated with AZA?
- bone marrow suppression, hepatotoxicity
what are the AEs associated with mycophenolate?
- leukopenia, GI intolerance (GI effects here are severe- people will sometimes be unable to leave their homes because of diarrhea)
NEVER use AZA and _____ together due to severe bone marrow suppression
allopurinol
What are other DIs associated with AZA?
- allopurinol
- ACE inhibitors (profound neutropenia)
- warfarin(decreased INR)
What are the drug interactions associated with mycophenolate?
- anitbiotics (may change enterohepatic recirculation, may change trough level but not necessarily overall exposure)
- cholestyramine (prevents reabsorption via enterohepatic recirculation, significant decrease in MPA concentration)
- PPIs (decreases MPA levels, use lowest dose possible)
- antacids (dose separated by 2 hours minimum)
- iron preps (dose seperation not required)
What is mycophenolate dependent on for absorption?
- dependent on pH for absorption- mycophenolate is pH dependent with its absorption - not based on chelation so this is why you need to space out antacids and not iron preps
What are the most common AE associated with corticosteroids?
- increaed lipids, increased BG, increased bp, sleep disturbances, increased appetite/weight, moos swings, osteoporosis, acne, fluid retention
What is a monitoring parameter for cyclosporine levels?
- want to ensure that the trough level (winning 30 minutes pre-dose)
- high variability of cyclosporine trough levels
- target level depends on time since transplant and is individual to each patient
- usual maintenance target range: 50-150 mcg/L
Trough levels of tacrolimis should correspond to what?
- to AUC/drug exposure
- target range in reference: 6-8 mcg/L
What is the target drug range for sirolimus?
AUC/drug exposure
- target level depends on time since transplant and is individual to each patient
- usual maintenance range: 6-10 mcg/L
What is the monitoring parameter associated with mycophenolate?
- these levels are not routinely done - wide inter-individual variability in MPA exposure
- no single time point here accurately reflects exposure
- some centres do trough levels in setting of toxicity or absorption concerns (target and dose adjustments are unclear)
Glucose control in these patients helps to ____ the TGs
decrease
What are the main reasons for dyslipidemia?
- CKD
- age
- lifestyle: diet, smoking, exercise
- prednisone
- cyclosporine
What immunosuppressent is there no interaction with statins?
- tacrolimis
What immunosuppressants have the most reports of myopathy?
- combination of CSA with a statin, there are a few with tacrolimis and sirolimus
What is the incidence of pneumocystis jiroveci?
- PJP has significant morbidity and mortality in solid organ transplant patients (mortality up to 50%)
- associated with periods of higher immunosupression (eg. first 3-12 months post-transplant)
- tx: co-trimoxazole 15-20 mg TMP/kg/day
- – 1600/3200 (2 DS tabs) q8h
Who is at the highest risk of CMV?
- when the donor has had CMV before and the recipient has not – more likely to get it this way
What is the prophylaxis treatment for CMV?
- valganciclovir 900 mg for 6 months
What are the problems associated with BK virus and renal transplantation?
- polyomavirus- reactive and replciate in an immunosuppressed state
- may lead to bk nephropathy and graft failure
- routine screening for BK viremia and graft dysfunction
- NO GOOD TX- switch to cyclosporin to reduce immunosuppression
What is the impact that an infection from EBV has on kidneys?
- common virus in the general population
- associated with a development of post transplant lymphoproliferative disorder
- lower immunosuppressive therapy!
What are the complications associated with UTIs and kidney transplants?
- can led to sepsis, graft dysfunction and failure
What are the risk factors associated with UTIs?
- females, advanced age history if UTIs pre transplant, prolonged use of a catheter, indwelling device, polycycstic kidney disease
Should UTIs be prophylaxed for?
- yes! there is benefit in the first 3 months
- TMPSMX is preferred over cipro
What are some of the common complications associated with renal transplantation?
- anemia (surgical blood loss, time for new kidney to start expo production
- analgesia- chronic pain
- decreased bone density due to steroid use
- increased blood pressure
- increased cholesterol (esp wit sirolimus use)
- increased cancer risk
- diabetes onset (with steroid use this is difficult to control)
- depression
- cataracts (due to steroid use)
- exercise
What drug is known to be teratogenic, and what should be done if someone is planning on getting pregnant?
- mycophenolate is known to be teratogenic
- switch women to azathioprine if planning on conceiving
- – recommend for women and men!
