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Clinical 2 (Sam) > Renal Transplants > Flashcards

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

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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
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3
Q

Living donors:

Grant survival ?

A

20-25 years

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4
Q

Living donors:

Pre-emptive ?

A

possible

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5
Q

Deceased donors:

Graft survival ?

A

13-15 years

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6
Q

Deceased donors:

Have a ____ time

A

wait

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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)

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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)

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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

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10
Q

How many kidney transplants can you have?

A

The most there is right now is someone with 4 extra kidneys.

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11
Q

Describe standard kidney transplant recipients

A

Low or high immunological risk based on HLA match, antibody memory

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12
Q

HLA

A

Human Leukocyte Antigens:
-HLA are markers on most cells that help to identify “self” from “foreign”
MHC in humans = HLA

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13
Q

Describe Class 1 types of HLA

A

Class 1: A, B, C

Stimulate T-killer cells

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14
Q

Describe Class 2 types of HLA

A

Class 2: DR, DP, DQ

Stimulate T-helper cells, macrophages, B-cells

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15
Q

A match is out of __

A

8

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16
Q

What type of donor would give you the best probability for an 8/8 match?

A

sibling (identical twin is best)

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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
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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
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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
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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
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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)

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22
Q

Intensive immunosuppressive therapy at time of transplant to reduce risk of acute _____

A

rejection

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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)

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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

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25
Q

Many difference combinations of maintenance regimens. What does the choice depend on?

A
  • Type of transplant
  • Match between donor and recipient
  • Underlying disease
  • Patient history
  • Co-morbidities
  • Medication tolerance
  • Patient age
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26
Q

What is the standard therapy for adult kidney transplant?

A

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

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27
Q

Describe the usual maintenance regimen?

A

1) T-cell communication
- Cyclosporine
- Tacrolimus

2) Anti-proliferative
- Azathioprine
- Mycophenolate
- Sirolimus

3) Prednisone
* Usually 1 from each box

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28
Q

Cyclosporine and Tacrolimus are examples of?

A

Calcineurin Inhibitors (CNIs)

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29
Q

30-40% of ppl after kidney transplant develop _____

A

diabetes

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30
Q

Adverse drug reactions with CNIs (cyclosporine and tacrolimus)

A
  • increase BG (tacrolimus)
  • increase BP
  • increases lipids
  • increases K+
  • decrease Mg+
  • decrease P
  • increase UA
  • tremor
  • nephro & hepatoxicity, gingival hyperplasia (CSA)
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31
Q

CNIs are both substrates and inhibitors of ______ and ____

A

CYP-3A4 and P-gp

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32
Q

Is cyclosporine or tacrolimus a better inhibitor of CYP 3A4?

A

cyclosporine

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33
Q

How does diarrhea affect cyclosporine/tacrolimus ?

A
  • 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

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34
Q

List some 3A4 inhibitors that will increase concentrations of cyclosporine or tacrolimus

A
  • Azoles
  • Macrolides
  • Non-DHP CCB’s
  • Grapefruit juice
  • Ritonovir/protease inhibitors
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35
Q

List some 3A4 inducers that will decrease concentrations of cyclosporine or tacrolimus

A
  • Rifampin
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • St. John’s Wort
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36
Q

Describe the drug interaction between cyclosporine & minoxidil

A

hirsutism (excessive body hair)

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37
Q

Describe the drug interaction between cyclosporine & phenytoin, nifedipine

A

gum hyperplasia

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38
Q

Describe the drug interaction between cyclosporine & statins, digoxin, caspofungin

A

decreased clearanceq

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39
Q

Describe the drug interaction between cyclosporine & colchicine

A

increased myopathy and hepatotoxicity

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40
Q

Describe the drug interaction between cyclosporine & glyburide

A

increased CSA level

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41
Q

Describe the drug interaction between cyclosporine & repaglinide

A

increased repaglinide exposure

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42
Q

Describe the drug interaction between cyclosporine & warfarin

A

decreased INR and CSA levels

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43
Q

Describe the drug interaction between cyclosporine & potassium sparing diuretics

A

hyperkalemia

44
Q

Which statins can you use with cyclosporine?

A

pravastatin or fluvastatin (still caution tho)

45
Q

Describe the drug interaction between tacrolimus & potassium sparing diuretics

A

hyperkalemia

46
Q

Describe the drug interaction between tacrolimus & metoclopramide

A

increased tacrolimus exposure

47
Q

Describe the drug interaction between tacrolimus & statins

A

TAC/atorvastatin might be okay

48
Q

Which NOAC is the safest with CNI’s?

A

Apixaban - likely “safer”

slide 41

49
Q

CNIs cause afferent & efferent ________

A

vasoconstriction

50
Q

Which drugs will cause additive nephrotoxicity with CNI’s?

A

NSAIDS: afferent vasoconstriction

ACEi/ARB: efferent vasodilation

Aminoglycosides, amphotericin B

51
Q

Which drugs will cause renal sparing?

A

CCBs: afferent vasodilation

52
Q

List an example of rapamycin derivatives?

A

sirolimus

53
Q

When is Sirolimus dosed in response to cyclosporine?

A

4 hours after cyclosporine

54
Q

SE of Sirolimus ?

A
  • increase lipids, proteinuria, delayed would healing, anemia, hypertension
  • caution in liver and lung transplant - hepatic artery stenosis, bronchial anastomotic dehiscence
55
Q

3A4 inhibitors will ______ concentrations of Sirolimus

A

increase

56
Q

3A4 inducers with _____ concentrations of Sirolimus

A

decrease

57
Q

Inducers of 3A4 will ____ concentrations of tacrolimus, sirolimus and cyclosporine

A

decrease

58
Q

List examples of inducers of 3A4

A
  • Rifampin
  • Phenytoin, carbamazepine, barbiturates
  • St. John’s Wort (avoid with CSA, TAC, SIR)
59
Q

Inhibitors of 3A4 will ______ concentrations of tacrolimus, sirolimus and cyclosporine

A

increase

60
Q

List examples of inhibitors of 3A4

A

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
Q

Inhibitors of P-gp will ____ concentrations of tacrolimus, sirolimus and cyclosporine

A

increase

62
Q

Inducers of P-gp will ______ concentrations of tacrolimus, sirolimus and cyclosporine

A

decrease

63
Q

How does diarrhea affect P-gp ?

A

Diarrhea depletes GI lining with P-gp

-Increased drug levels/exposure (also it’s own cause of GI distrubances)

64
Q

List examples of Anti-Proliferatives

A

Azathioprine, Mycophenolate

65
Q

ADRs of Azathioprine

A
  • bone marrow suppression

- hepatotoxicity

66
Q

ADRs of Mycophenolate

A

leukopenia, GI intolerance

67
Q

What is TMPT phenotype to guide dosing of azathioprine?

A

TMPT is a genetic test - it’s an enzyme, you check and see if it’s normal levels this enzyme breaks down azathioprine

68
Q

Describe the drug interaction between:

Azathioprine & Allopurinol

A
  • Avoid using allopurinol while on AZA
  • Significantly increases AZA levels
  • Profound neutropenia
69
Q

Describe the drug interaction between:

Azathioprine & ACEi

A

increased neutropenia

70
Q

Describe the drug interaction between:

Azathioprine & Warfarin

A

decreased INR

71
Q

Describe the interaction between:

Mycophenolate & Antibiotics

A

may change enterohepatic recirculation (may change trough level but not necessarily overall exposure)

72
Q

Describe the interaction between:

Mycophenolate & Cholestyramine

A
  • Prevents reabsorption via enterohepatic recirculation

- Significant decrease in MPA concentration

73
Q

Describe the interaction between:

Mycophenolate & PPIs

A

Decrease Mycophenolate levels, use lowest dose possible

74
Q

Describe the interaction between:

Mycophenolate & Antacids

A

Dose separation by 2 hours minimum

75
Q

Describe the interaction between:

Mycophenolate & iron preparations

A

dose separation not required

76
Q

Why is dose separation not required for iron but it is required for antacids?

**with mycophenolate

A

Bc we think mycophenolate absorption is pH dependent

  • Antacids affect pH
  • Iron dose not
77
Q

List 2 corticosteroids

A

Prednisone, methylprednisone

78
Q

Adverse drug reactions of corticosteroids?

A

-increase lipids, increase BG and BP, sleep disturbances, increase appetite/weight, mood swings, osteoporosis, acne, fluid retention

79
Q

Drug interactions with corticosteroids?

A

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
Q

From Case #1:

You are starting phenytoin but they are tacrolimus. What do you do?

A

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
Q

Describe the monitoring after a kidney transplant

A

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
Q

Target blood concentrations must correlate with what?

A
  • Exposure (i.e. AUC)

- Clinical outcomes - therapeutic and toxic

83
Q

What factors influence pharmacokinetics of CNI?

A
  • 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
Q

go over monitoring slides on slide 67

A

okay

85
Q

Case #2

What else do you want to know?

A
  • 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
Q

What are some reasons for dyslipidemia?

A
  • CKD
  • Age
  • Lifestyle: diet, exercise, smoking
  • Prednisone
  • Cyclosporine
87
Q

Which statins can you use with cyclosporine?

A

pravastatin and fluvastatin (caution tho)

88
Q

Which statins can you use with tacrolimus?

A

nothing mentioned

no data vs. no interaction

89
Q

Which statins can you use with sirolimus?

A

atorvastatin

90
Q

lipids and CV disease is common in _____

A

transplants

91
Q

Which immunosuppressant and statin combo has the most reports of rhabdomyolysis/myositis?

A

Cyclosporine

92
Q

Post-transplant infections:

Describe PCP/PJP

A

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
Q

Post-transplant infections:

What is the prophylaxis for PCP?

A

In Mb:

  • 3 months
  • Co-trimoxazole 400/80 mg daily or 800/160 mg EOD/MWF
94
Q

Post-transplant infections:

What is the treatment for PCP?

A
  • 3 weeks
  • Co-trimoxazole (oral/IV) 15-20 mg TMP/kg/day
  • approx 1600/320 mg (2 DS tabs) q8h
95
Q

Post-transplant infections:

Describe CMV

A

-CMV is a member of the herpes virus family

96
Q

Post-transplant infections:

What is the prophylaxis for CMV?

A

Pre-emptive treatment until 2 negative PCR

Valganciclovir 900 mg daily for 6 months

97
Q

Post-transplant infections:

Describe BK Virus

A
  • 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
Q 
Post-transplant infections:
Describe EBV (mono)
A
  • 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
Q

Post-transplant infections:

Describe UTI

A
  • 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
Q

Post-transplant:

When is it okay to give vaccines and which type?

A

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
Q

Post-transplant increases risk for ______

A

malignancy/cancer

102
Q

What are some complications of renal transplants?

A
  • Anemia
  • Analgesia for pain
  • Bone density decrease
  • Blood pressure increase
  • Cholesterol increase
  • Cancer risk
  • Diabetes/increased BG
  • Depression/mood changes
  • Eyes (cataracts)
  • Exercise
103
Q

Describe mycophenolate & fertility

A
  • Known to be teratogenic in females

- Switch to azathioprine if planning for pregnancy

104
Q

Goals of transplant

A
  • Prolong graft survival
  • Prevent rejection episodes
  • Assess adherence on a regular basis
  • Minimize long term complications
105
Q

What should you do if you have a transplant recipient at your pharmacy ?

A
  • 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
Q

KNOW THE TARGET RANGES FOR THE DIFFERENT LEVELS

A

ok dude

Clinical 2 (Sam) (18 decks)

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