Renal Transplants Flashcards
1
Q
List some benefits of renal transplantation
A
- Not life saving (as for liver, lung, heart transplant)
- Kidney transplantation is another means of renal replacement therapy
- The sickest patient does not necessarily get a kidney transplant first
- Survival benefit
- Improved quality of life
- Cost saving (after the 1st year post transplant)
*kidney transplants are an alternative to dialysis
2
Q
Which patients are high priority?
A
- Children (need kidneys for normal development)
- People on dialysis but lost line access and can no longer receive dialysis
- Younger kidneys go to younger patients
- People who previously donated a kidney
3
Q
Living donors:
Grant survival ?
A
20-25 years
4
Q
Living donors:
Pre-emptive ?
A
possible
5
Q
Deceased donors:
Graft survival ?
A
13-15 years
6
Q
Deceased donors:
Have a ____ time
A
wait
7
Q
List the 3 types of living kidney donors
A
1) Direct donation (ex. family or friend)
2) Kidney paired exchange (KPD)
3) Altruistic, non-directed (just want to donate a kidney and help someone out - anonymous)
8
Q
List the 3 types of deceased kidney donors
A
1) Neurological determination death (NDD)
- brain dead
2) Donation after cardiac death (DCD)
3) Medical assistance in dying (MAID)
9
Q
List the 4 parts to describing donor quality
A
1) Standard criteria donor
2) Extended criteria donor
3) High infectious risk donor
4) Exceptional distribution donor
10
Q
How many kidney transplants can you have?
A
The most there is right now is someone with 4 extra kidneys.
11
Q
Describe standard kidney transplant recipients
A
Low or high immunological risk based on HLA match, antibody memory
12
Q
HLA
A
Human Leukocyte Antigens:
-HLA are markers on most cells that help to identify “self” from “foreign”
MHC in humans = HLA
13
Q
Describe Class 1 types of HLA
A
Class 1: A, B, C
Stimulate T-killer cells
14
Q
Describe Class 2 types of HLA
A
Class 2: DR, DP, DQ
Stimulate T-helper cells, macrophages, B-cells
15
Q
A match is out of __
A
8
16
Q
What type of donor would give you the best probability for an 8/8 match?
A
sibling (identical twin is best)
17
Q
Describe “sensitizing events” that can lead to anti-HLA antibody and make it harder to find a match
A
- pregnancy
- blood transfusions
- previous transplants
18
Q
What is a PRA screening
A
Panel Reactive Antibody screening
- Degree of “transplantability”
- 60% PRA = incompatibility for transplant with about 60 out of 100 potential donors (of same blood group)
- 95% PRA - highly sensitized, separate registry
19
Q
What is cross-matching?
What result is bad?
A
- A test between donor and recipient
- HLA antibodies can cause severe rejection and graft loss
- Positive cross match is BAD
- The recipient’s cells are able to recognize and attack the donor cells. This causes an increased risk of rejection
20
Q
Sometimes a person develops antibodies to the donor after the transplant, often a result of ?
A
- Often result of non-compliance, under immunosuppression
- 6x increased risk for graft loss
- 56% 10 year graft survival
21
Q
How do we achieve immunosuppression ?
A
1) Depletion of lymphocytes (depleting antibodies)
2) Blocking of lymphocyte response
- Non-depleting monoclonal antibody IL-2 receptor antagonists (basiliximab)
- Calcineurin inhibitors (tacrolimus, cyclosporine)
- Anti-proliferative agents (azathioprine, mycophenolic acid)
- mTOR inhibitor (sirolimus)
22
Q
Intensive immunosuppressive therapy at time of transplant to reduce risk of acute _____
A
rejection
23
Q
What agents do we use for immunosuppressants (induction therapy)? (3)
A
1) Depleting antibodies
- Anti-thymocyte: Thymoglobulin
2) Non-depleting antibodies
- IL-2 (CD25) receptor: Basiliximab
3) Corticosteroids (predinosine, methylprednisilone)
24
Q
What agents do we use for immunosuppressants (maintenance therapy)? (4)
A
1) Calcineurin inhibitors (CNIs)
- Cyclosporine
- Tacrolimus IR
- Tacrolimus ER
2) Corticosteroids
- Prednisone
- Methylprednisilone
3) Antiproliferatives
- Azathioprine
- Mycophenolate mofetil
- Mycophenolate sodium
4) Rapamycins derivatives
- Sirolimus
25
Many difference combinations of maintenance regimens. What does the choice depend on?
- Type of transplant
- Match between donor and recipient
- Underlying disease
- Patient history
- Co-morbidities
- Medication tolerance
- Patient age
26
What is the standard therapy for adult kidney transplant?
1) Tacrolimus (Program or Advagraf)
- Inhibits early in T-cell activation + clonal expansion
2) Mycophenolate mofetil
- Works to decrease T-cell proliferation
3) Prednisone
- Sequesters and inhibits lymphocytes
27
Describe the usual maintenance regimen?
1) T-cell communication
- Cyclosporine
- Tacrolimus
2) Anti-proliferative
- Azathioprine
- Mycophenolate
- Sirolimus
3) Prednisone
* Usually 1 from each box
28
Cyclosporine and Tacrolimus are examples of?
Calcineurin Inhibitors (CNIs)
29
30-40% of ppl after kidney transplant develop _____
diabetes
30
Adverse drug reactions with CNIs (cyclosporine and tacrolimus)
- increase BG (tacrolimus)
- increase BP
- increases lipids
- increases K+
- decrease Mg+
- decrease P
- increase UA
- tremor
- nephro & hepatoxicity, gingival hyperplasia (CSA)
31
CNIs are both substrates and inhibitors of ______ and ____
CYP-3A4 and P-gp
32
Is cyclosporine or tacrolimus a better inhibitor of CYP 3A4?
cyclosporine
33
How does diarrhea affect cyclosporine/tacrolimus ?
- diarrhea can cause sloughing of intestinal endothelium
- loss of P-gp
- increased CNI levels
*other meds may use P-gp and this can affect them too
34
List some 3A4 inhibitors that will increase concentrations of cyclosporine or tacrolimus
- Azoles
- Macrolides
- Non-DHP CCB's
- Grapefruit juice
- Ritonovir/protease inhibitors
35
List some 3A4 inducers that will decrease concentrations of cyclosporine or tacrolimus
- Rifampin
- Phenytoin
- Carbamazepine
- Phenobarbital
- St. John's Wort
36
Describe the drug interaction between cyclosporine & minoxidil
hirsutism (excessive body hair)
37
Describe the drug interaction between cyclosporine & phenytoin, nifedipine
gum hyperplasia
38
Describe the drug interaction between cyclosporine & statins, digoxin, caspofungin
decreased clearanceq
39
Describe the drug interaction between cyclosporine & colchicine
increased myopathy and hepatotoxicity
40
Describe the drug interaction between cyclosporine & glyburide
increased CSA level
41
Describe the drug interaction between cyclosporine & repaglinide
increased repaglinide exposure
42
Describe the drug interaction between cyclosporine & warfarin
decreased INR and CSA levels
43
Describe the drug interaction between cyclosporine & potassium sparing diuretics
hyperkalemia
44
Which statins can you use with cyclosporine?
pravastatin or fluvastatin (still caution tho)
45
Describe the drug interaction between tacrolimus & potassium sparing diuretics
hyperkalemia
46
Describe the drug interaction between tacrolimus & metoclopramide
increased tacrolimus exposure
47
Describe the drug interaction between tacrolimus & statins
TAC/atorvastatin might be okay
48
Which NOAC is the safest with CNI's?
Apixaban - likely "safer"
slide 41
49
CNIs cause afferent & efferent ________
vasoconstriction
50
Which drugs will cause additive nephrotoxicity with CNI's?
NSAIDS: afferent vasoconstriction
ACEi/ARB: efferent vasodilation
Aminoglycosides, amphotericin B
51
Which drugs will cause renal sparing?
CCBs: afferent vasodilation
52
List an example of rapamycin derivatives?
sirolimus
53
When is Sirolimus dosed in response to cyclosporine?
4 hours after cyclosporine
54
SE of Sirolimus ?
- increase lipids, proteinuria, delayed would healing, anemia, hypertension
- caution in liver and lung transplant - hepatic artery stenosis, bronchial anastomotic dehiscence
55
3A4 inhibitors will ______ concentrations of Sirolimus
increase
56
3A4 inducers with _____ concentrations of Sirolimus
decrease
57
Inducers of 3A4 will ____ concentrations of tacrolimus, sirolimus and cyclosporine
decrease
58
List examples of inducers of 3A4
- Rifampin
- Phenytoin, carbamazepine, barbiturates
- St. John's Wort (avoid with CSA, TAC, SIR)
59
Inhibitors of 3A4 will ______ concentrations of tacrolimus, sirolimus and cyclosporine
increase
60
List examples of inhibitors of 3A4
Diltiazem, verapamil: immunosuppressant dose reductions of 25-50%
Azole antifungals: avoid if possible (esp. voriconazole)
-Single dose fluconazole has minimal effect
Erythromycin, clarithromycin: avoid if possible
Grapefruit
61
Inhibitors of P-gp will ____ concentrations of tacrolimus, sirolimus and cyclosporine
increase
62
Inducers of P-gp will ______ concentrations of tacrolimus, sirolimus and cyclosporine
decrease
63
How does diarrhea affect P-gp ?
Diarrhea depletes GI lining with P-gp
| -Increased drug levels/exposure (also it's own cause of GI distrubances)
64
List examples of Anti-Proliferatives
Azathioprine, Mycophenolate
65
ADRs of Azathioprine
- bone marrow suppression
| - hepatotoxicity
66
ADRs of Mycophenolate
leukopenia, GI intolerance
67
What is TMPT phenotype to guide dosing of azathioprine?
TMPT is a genetic test - it's an enzyme, you check and see if it's normal levels this enzyme breaks down azathioprine
68
Describe the drug interaction between:
| Azathioprine & Allopurinol
- Avoid using allopurinol while on AZA
- Significantly increases AZA levels
- Profound neutropenia
69
Describe the drug interaction between:
| Azathioprine & ACEi
increased neutropenia
70
Describe the drug interaction between:
| Azathioprine & Warfarin
decreased INR
71
Describe the interaction between:
| Mycophenolate & Antibiotics
may change enterohepatic recirculation (may change trough level but not necessarily overall exposure)
72
Describe the interaction between:
| Mycophenolate & Cholestyramine
- Prevents reabsorption via enterohepatic recirculation
| - Significant decrease in MPA concentration
73
Describe the interaction between:
| Mycophenolate & PPIs
Decrease Mycophenolate levels, use lowest dose possible
74
Describe the interaction between:
| Mycophenolate & Antacids
Dose separation by 2 hours minimum
75
Describe the interaction between:
| Mycophenolate & iron preparations
dose separation not required
76
Why is dose separation not required for iron but it is required for antacids?
**with mycophenolate
Bc we think mycophenolate absorption is pH dependent
- Antacids affect pH
- Iron dose not
77
List 2 corticosteroids
Prednisone, methylprednisone
78
Adverse drug reactions of corticosteroids?
-increase lipids, increase BG and BP, sleep disturbances, increase appetite/weight, mood swings, osteoporosis, acne, fluid retention
79
Drug interactions with corticosteroids?
Minimal but do interact with:
- Immune stimulants
- Decongestants
- PPIs - use lowest possible dose
- Additive nephrotoxicity: avoid when possible with NSAIDs and ahminoglycosides, and amphotericin B
80
From Case #1:
| You are starting phenytoin but they are tacrolimus. What do you do?
No need to pre-emptively lower doses. Take blood levels and adjust accordingly.
Phenytoin = 3A4 inducer so it will decrease TAC level
-Increase TAC level by 25%
81
Describe the monitoring after a kidney transplant
Managing drug levels of a transplant patient is like balancing a scale:
- Rejection (efficacy vs toxicity)
- Each person and each target level is unique
- Never a textbook case
Within each "reference range", the appropriate drug level (tighter range) is influenced by:
- Time post-transplant
- Organ type
- Use of induction agents
- Other immunosuppression
- Presence of rejection or toxicity
82
Target blood concentrations must correlate with what?
- Exposure (i.e. AUC)
| - Clinical outcomes - therapeutic and toxic
83
What factors influence pharmacokinetics of CNI?
- Age
- Race
- Type of organ
- Liver dysfunction
- Hep c
- Small bowel length
- Gastrintestinal state
- Infection
- Inflammatory states
- Time post-transplant
- Hematocrit
- Albumin levels
- Diurnal variations
- Drug interactions
- Comorbidities (diabetes, CHF)
- Intestinal CYP 450 and P-gp expression
84
go over monitoring slides on slide 67
okay
85
Case #2
| What else do you want to know?
- BMI, waist circumference
- Diet and exercise and smoking history
- CVD history (personal and family)
- Abnormal baseline renal function
- Why cyclosporine vs tacrolimus?
- Lipid target ? lol
86
What are some reasons for dyslipidemia?
- CKD
- Age
- Lifestyle: diet, exercise, smoking
- Prednisone
- Cyclosporine
87
Which statins can you use with cyclosporine?
pravastatin and fluvastatin (caution tho)
88
Which statins can you use with tacrolimus?
nothing mentioned
| no data vs. no interaction
89
Which statins can you use with sirolimus?
atorvastatin
90
lipids and CV disease is common in _____
transplants
91
Which immunosuppressant and statin combo has the most reports of rhabdomyolysis/myositis?
Cyclosporine
92
Post-transplant infections:
| Describe PCP/PJP
Pneumocystis jiroveci:
- PJP has significant morbidity and mortality in solid organ transplant patients
- Associated with periods of higher immunosuppression in the first 3-12 months post-transplant
93
Post-transplant infections:
What is the prophylaxis for PCP?
In Mb:
- 3 months
- Co-trimoxazole 400/80 mg daily or 800/160 mg EOD/MWF
94
Post-transplant infections:
What is the treatment for PCP?
- 3 weeks
- Co-trimoxazole (oral/IV) 15-20 mg TMP/kg/day
- approx 1600/320 mg (2 DS tabs) q8h
95
Post-transplant infections:
| Describe CMV
-CMV is a member of the herpes virus family
96
Post-transplant infections:
| What is the prophylaxis for CMV?
Pre-emptive treatment until 2 negative PCR
Valganciclovir 900 mg daily for 6 months
97
Post-transplant infections:
| Describe BK Virus
- Polyomavirus
- Common in general population, mostly asymptomatic in the renal tract
- Reactive and replicate in immunosuppressed state
- May lead to BK nephropathy and graft failure
- Routine screening for BK viraemia & graft dysfunction
- No good treatments available (reduction in baseline immunosuppression, switch to cyclosporine)
98
```
Post-transplant infections:
Describe EBV (mono)
```
- Common virus in general population
- Routine screening if EMB mismatch at time of transplant
- Association with development of post transplant lymphoproliferative disorder
- Mainstay treatment - lowering immunosuppressive therapy
99
Post-transplant infections:
| Describe UTI
- Most common infection post kidney transplant
- Pyelonephritis can lead to sepsis, graft dysfunction and failure
- Risk factors include female, advanced age, history of UTI's pre-transplant, prolonged use of catheter, indwelling device, polycystic kidney disease
- There is benefit to using UTI prophylaxis especially within first 3 months post kidney transplant
- TMP/SMX is preferred over ciprofloxacin
100
Post-transplant:
| When is it okay to give vaccines and which type?
Avoid live vaccines!
Inactivated vaccines only.
Flu shot is okay 3 months after transplant, should wait 6 months after transplant for other inactivated vaccines.
101
Post-transplant increases risk for ______
malignancy/cancer
102
What are some complications of renal transplants?
- Anemia
- Analgesia for pain
- Bone density decrease
- Blood pressure increase
- Cholesterol increase
- Cancer risk
- Diabetes/increased BG
- Depression/mood changes
- Eyes (cataracts)
- Exercise
103
Describe mycophenolate & fertility
- Known to be teratogenic in females
| - Switch to azathioprine if planning for pregnancy
104
Goals of transplant
- Prolong graft survival
- Prevent rejection episodes
- Assess adherence on a regular basis
- Minimize long term complications
105
What should you do if you have a transplant recipient at your pharmacy ?
- Find out who their transplant team is
- Remember drug interactions
- The ABCDE list is a great way to look for areas to improve their overall health
- Ask about adherence
106
KNOW THE TARGET RANGES FOR THE DIFFERENT LEVELS
ok dude
