Kidney Transplantation: An Overview Of Immunosuppression

Front 1

What are the 6 Rejection Risk Stratifications?

Back 1

Donor Source
Living donor
Related or unrelated
Deceased Donor
DBD (brain) or DCD (cardiac)
Extended Criteria Donors (ECD)

Matching (ABO blood typing)

Panel Reactive Antibody (PRA)

Primary vs. multiple transplants

Race

Age

Front 2

What is a Panel Reactive Antibody? Who is performed on and what does it measure?

Back 2

Panel Reactive Antibody (PRA) is a blood test that is routinely performed on patients waiting for kidney and and measures anti-human antibodies in the blood.

Front 3

What does the PRA represent?

Back 3

The PRA represents the percentage of the U.S. population that the anti-human antibody in your blood reacts with.

Front 4

What scores are good PRA?

What scores are bad?

Back 4

High PRA not good
Low PRA is good

Front 5

What are the 3 types of rejections?

Back 5

Hyperacute

Acute

Chronic

Front 6

What kind of onset is the:
Onset?
Cause?
Prevention?

For hyperacute?

Back 6

Onset: Instant
Cause: Preformed antibodies
Prevention: Blood typing

Front 7

What kind of onset is the:
Onset?
Cause?
Prevention?

For acute

Back 7

Onset: Days or more
Cause: T-Cells; Cytokines
Prevention: Immunosuppressive Medication

Front 8

What kind of onset is the:
Onset?
Cause?
Prevention?

For chronic

Back 8

Onset: Months or more
Cause: (?) B-Cells; Endothelium
Prevention: (?) Prevent acute rejection

Front 9

What are the three immunosuppressove strategies?

Back 9

Induction

Maintenance

Rejection

Front 10

2 Calcineurin Inhibitors

Back 10

Tacrolimus
Cyclosporine

Front 11

2 steroids

Back 11

Methyprednisolone
Prednisone

Front 12

1 Monoclonal Antibodies

Back 12

Basiliximab

Front 13

3 antimetabolites

Back 13

Mycophenolate mofetil
Mycophenolic acid
Azathioprine

Front 14

2 mTOR Inhibitors

Back 14

Sirolimus
Everolimus

Front 15

What are 6 goals of Immunosuppression in solid organ transplant (SOT)

Back 15

1.To prevent allograft rejection
2.To prolong allograft functional life
3.To optimize allograft function

4.Prolong patient survival
5.Improve patient quality of life
6.To minimize toxicity of IMS agents
non-immune toxicities
Immunodeficiency complications

Front 16

What is the MOA of Thymoglobulin?

Back 16

Polyclonal Antibody
Antibody against human T-cells
Depletion of peripheral blood lymphocytes

Front 17

What are the uses for Thymoglobulin?

Back 17

Induction
Treatment of steroid resistant rejection

Front 18

What is the dosing for Thymoglobulin?

Back 18

1.5mg/kg IV over 4-6 hrs
(2-14 doses) induction vs rejection
Central or Peripheral Line
Premedicate

Front 19

What are the AEs of Thymoglobulin?

Back 19

Infusion related reactions
Serum sickness
Thrombocytopenia
Leukopenia
Anaphylaxis
Infections/PTLD

Front 20

What is the brand name of basiliximab?

Back 20

Simulect

Front 21

Simulect (basiliximab) MOA?

Back 21

Monoclonal Antibody

Block CD25 (IL-2 receptor) on activated T cell

Blocks the normal physiologic cascade of events initiated by IL-2

Front 22

What are the uses of Simulect (basiliximab)?

Back 22

Induction

Front 23

What is the dosing of Simulect?

Back 23

Simulect: 20mg IV over 30 minutes x2 on POD 0 and POD 4
No premedication

Front 24

Is Simulect as potent as thymoglobulin?

Back 24

Less potent than Thymoglobulin.

Front 25

What 2 drugs are responsible for Induction?

Back 25

Thymoglobulin >> Basiliximab

Front 26

When do you use basiliximab?

Back 26

Low/moderate risk kidney recipients
Exposure to rabbits

Front 27

When is thymo used?

Back 27

Moderate/high risk kidney recipients

Front 28

What are brand names of cyclosporine?

Back 28

Neoral, Gengraf, Sandimmune, CSA)

Front 29

What are brand names of tacrolimus?

Back 29

(Prograf, FK-506)

Front 30

What are brand names and drug class Azathioprine

Back 30

Imuran, AZA)
Antiproliferative Agents

Front 31

What are brand names and drug class
Mycophenolate Mofetil

Back 31

Cellcept, MMF)

Antiproliferative Agents

Front 32

What are brand names and drug class
Mycophenolic Acid

Back 32

Myfortic, MPA)
Antiproliferative Agents

Front 33

What are brand names and drug class Sirolimus

Back 33

mTOR inhibitors

Rapamune, Rapamycin)

Front 34

What are brand names and drug class Everolimus

Back 34

mTOR inhibitors

Zortress)

Front 35

What are brand names and drug class
Prednisone

Back 35

Deltasone)

Corticosteroids

Front 36

What are brand names and drug class
Methylprednisolone

Back 36

Solu-Medrol)

Corticosteroids

Front 37

Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) MOA?

Back 37

Forms a complex with cyclophilin/FKBP

Complex binds/inhibits calcineurin phosphatase (CNP)

CNP prevents NFAT from entering nucleus

Inhibits IL-2 production
Necessary for full T cell activation

Front 38

Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) Bioavailability?

Back 38

Variable
Decreased by food

Front 39

What is the dosing for (CSA) Neoral/Sandimmune

What is the dosing for Prograf (tacrolimus, FK 506)

Back 39

CSA: generally ~2 to 4 mg/kg/dose BID
target trough 150-300ng/ml

FK: generally ~0.05mg/kg/dose PO BID
target trough ~5-12ng/ml.

Front 40

Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) metabolism?

Back 40

Cytochrome P 450 3A4
P-Glycoprotein

Front 41

do you take Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) with or without food?

Back 41

Without food –get stomach upset—TAKE WITH FOOD since dose based on trough levels.

Front 42

What are the dose conversions for cyclosporine and how long do you infuse it for?

Back 42

Cyclosporine PO:IV = ~3:1

Infuse over 2-4 h cyclosporine

Front 43

What are the dose conversions for tacrolimus and how long do you infuse it for?

Back 43

PO:IV = ~4:1

24 h for tacrolimus

Front 44

What kind of formulation is Sandimmune?

What is Neoral?

Back 44

Sandimmune – Original formulation

Neoral – Microemulsion formulation

Front 45

What drugs are cyclosporine modified

Which are cyclospirine non-modifed?

Back 45

Neoral, Gengraf)

(Sandimmune)

Front 46

Neoral – Microemulsion formulation

Has decreased __ ___
Better correlation with wihat?

LEss __ ___ absorption

Back 46

Decreased intra-patient variability
Better correlation with trough and AUC levels
Less bile dependent absorption

Front 47

GenGraf – Generic Cyclosporine (modified) is which drugs bioequivlant?

Back 47

Neoral

Front 48

Sandimmune is __ ___ for absorption

Back 48

bile dependent

Front 49

What are cyclosporines AEs

Back 49

Nephrotoxicity
Hypertension
GI effects (N,V,D)
Headache
Electrolyte effects
Tremors
Hyperlipidemia
Gingival hypertrophy
HIrsutism

Front 50

What are Tacrolimus AEs

Back 50

Nephrotoxicity
Hypertension
GI effects (N,V,D)
Headache
Electrolyte effects
Tremors and seizures
Post transplant DM
Hair loss

Front 51

Explain cyclosporins and tarcolimus electrolytes effect

Back 51

Increased potassium and DECREASED Phos and Mg
Ginigival hypertrophy reversible if we switch to different drug.

Front 52

Grand mal seizures are more prevelant in which drug?

Back 52

more prevalent with tacrolimus

Front 53

Out of tacrolimus and cyclosporine which has cardiovascular effects and nephrotoxic effects?

Back 53

more cardiovascular issues with cyclosporine than tacro but more neurotoxicity seen with tacro.

Front 54

What drugs increase effects on concentrations with Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) because they inhibit cyp 3a4 metabolism?

Back 54

Macrolides: Azithromycin does not effect
Erythromycin and Calrithromycin effects

Azoles: Fluconazole and voriconazole effect them

CCB: diltiazem and verapamil effect them

Danazol, chloramphenicol, cimetidine and grape fruit juice effect them

Front 55

What drugs decrease effects in concentration with Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) because they inhibit cyp 3a4 metabolism?

Back 55

Anticonvulsants: Phenytoin, phenobarbital, carbamazepine

Rifampin
Dexamethasone
Prednisone
St. John's Wort

Front 56

What does Cellcept (MMF) and Myfortic (MPA) prevent?
Compare there efficacy?
MAJOR SIDE EFFECT?
HOw many peaks to they get?
How many peaks do they get with cyclosprine?

Back 56

Both prevent proliferaton of T-Cells
Efficacy and safety same in both
Leukopenia major myelosuppressive side effect
MMF and MPA secreted in bile, and bile is reabsorped therefore usually has two peaks, when given with cyclosporine may not get the second peak.

Front 57

What is the moa of Cellcept (MMF) and Myfortic (MPA)

Back 57

MMF is a prodrug of MPA
Both reversiby inhibit inosine monophosphate dehydrogenase (IMPDH)
Block de novo purine synthesis

Front 58

What is the dosing for MMF?

What is the dosing for MPA?

Back 58

MMF: 1gm PO BID

MPA: 720mg PO BID
Do NOT break or crush

Front 59

What is a major SE for MMF and MPA?

Back 59

Leukopenia major myelosuppressive side effect

Front 60

What drug decreases AUC with MMF and and MPA?

Back 60

Cyclosporine decreases AUC

Front 61

What drug needs to be avoided giving with MMF or MPA?

Back 61

Cholestyramine-avoid!

Front 62

What OTC should be given seperately during admin when patient is on MMF and MPA?

Back 62

Antacids-separate admin!

Front 63

What kind of pts can you not use MMF and MPA?

Back 63

Pregnancy because they are teratogenic

Front 64

What is the prodrug of Imuran (azathioprine)?

Back 64

Prodrug of 6-mercaptopurine

Front 65

What is the MOA of Imuran?

Back 65

6-MP is incorporated into DNA where it interferes with RNA synthesis

Blocks proliferation of T cells

Front 66

What is the dosing of Imuran?

Back 66

~2mg/kg once daily

Front 67

What are the AEs of Imuran?

Back 67

Myelosuppression
Macrocytic anemia
Pancreatitis
Hepatotoxicity

Front 68

What drug interacts with Imuran?

Back 68

Allopurinol
Decrease AZA dose by 1/3 to ½ per PI
Contraindicated in practice!

Front 69

What is the MOA of Rapamune (sirolimus) andZortress (everolimus)?

Back 69

Binds FKBP
Complex interacts with the target of rapamycin (TOR)
Disrupts ability of IL-2 to trigger T cell division

Front 70

What is the dosing for Rapamune (sirolimus) andZortress (everolimus)?

Back 70

Rapamune: 6mg load then 2 mg daily
Target trough~3-15 ng/ml

Zortress: No load required, shorter half-life
1.5 to 3mg daily

Front 71

What kind of Metabolism does Rapamune (sirolimus) andZortress (everolimus) have?

Back 71

cyp 3A4

Meaning anything that inhibits it is a DI

Front 72

What are Aes of Rapamune (sirolimus) andZortress (everolimus)

Back 72

Impaired wound healing
Hyperlipidemia
Myelosuppression
GI effects (N,V,D)
Mouth ulcers

Front 73

What is the MOA of High Dose > 100mg of prednisone equivalents

Back 73

Directly toxic to T cells

Front 74

What is the MOA of SteroidsMethylprednisolone and Prednisone Low Dose < 100mg of prednisone equivalents

Back 74

Nonspecific immunosuppression: inhibits IL-1, IL-2, IL-3, IL-6, IL-15, TNF-alpha and INF-gamma

Front 75

Methylprednisolone and Prednisone
High doses at induction and maintenance usually___ per day.

Back 75

5mg

Usually instituion specfic

Front 76

What are AEs of SteroidsMethylprednisolone and Prednisone

Back 76

Decreased Growth Rate
Infections
Osteoporosis
Glucose Intolerance
Acne
Mood Alterations
Weight Gain

Front 77

What is the 1st agent always used?

What is the 2nd agent often used?

Back 77

Use of 2 or 3 agents with different MOAs
Agent #1 is always CNI
Agent #2 is often antimetabolite

Front 78

What drug class of drugs are the Back bone regimen?

Back 78

CNI
Backbone of regimen: Tacro >CSA

Front 79

What drugs are great adjunctive agents?

Back 79

Great adjunctive agents: MMF = MPA >AZA

Front 80

When are mTor inhibitors avoided?

If patients can tolerate a statin shoul they been on sirolimus?

Back 80

Typically avoided first 3 months to allow wound healing
If pt cannot tolerate a statin, should not be on sirolimus/everolimus

Front 81

Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
For viral prophylaxis what drugs should be used?
High risk?
Mod risk?
Low risk?

Back 81

High risk ( Donor +/Recipient-) Valganciclovir 450mg QD x 6 months

Mod risk (D+/R-) Valganciclovir 450mg Qd x 3 months

Low risk (D-/R-) Acyclovir 400mg q8h x 3 months

Front 82

Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
PCP prophylaxis (i.e. Pneumocystis jiroveci)?

Back 82

Bactrim SS daily x 6 months

Alternatives: Pentamidine, Atovaquone

Front 83

Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
UTI prophylaxis?

Back 83

Bactrim SS daily
Alternatives: any FQ except for Avelox

Front 84

Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
Fungal prophylaxis?

Back 84

Clotrimazole troche 1 lozenge tid x 1 month.