Solid Organ Transplant Flashcards by Reagan Smith

Terminology

Autotransplantation

Transplant of tissue from 1 part of the body to another

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Terminology

Allotransplantation

Transplant of tissue from 1 person to another person

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Terminology

Xenotransplantation

Transplant of tissue from a different species

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Terminology

Orthotopic

Transplanted into recipient in the same place (ex. heart, lung)

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Terminology

Heterotopic

Transplanted into recipient in a different place (ex. kidney)

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Pre-Transplant Immunologic Evaluation & Management

universal donor: ___
universal recipient: ___

group O
group AB

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Pre-Transplant Immunologic Evaluation & Management

HLA Typing (A, B, DR)
___ / ___ Complex
- An association of genes found on short arm of chromosome 6 that play an important role in immune recognition and response
- HLA compatibility assessed by number of HLA mismatches (or matches) of the donor

MHC, HLA

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Pre-Transplant Immunologic Evaluation & Management

HLA Antibodies
Do NOT occur naturally
- Formed in response to non-self HLA
exposure, “Sensitizing events”

Pre-transplant HLA donor-specific antibodies (DSA) = ___ in deceased donor transplants

Post-transplant DSA: development
indicates failure of ___
- de novo DSA

Blood transfusions, pregnancy, previous transplant = sensitizing events

contraindicated
immunosuppression

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Pre-Transplant Immunologic Evaluation & Management

Quantified as % of the panel to which the patient has developed antibody
- The higher the PRA = increased ___ to MHC antigens

Determination of Crossmatch
- Negative result must be obtained prior to transplant
- Testing the transplant recipient’s serum against donor ___ to determine if there is preformed anti-HLA Class I antibody

sensitization
T cells

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Pre-Transplant Immunologic Evaluation & Management

Panel Reactive Antibody (PRA)
- Amount of ___ HLA antibodies in a recipient compared to general population
- Higher PRA = ___ risk of rejection and longer wait times for an organ (> 20–30% generally considered sensitized)
- PRA can be checked multiple times while patients are on the waitlist

pre-formed
increased

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Pre-Transplant Immunologic Evaluation & Managemen

Crossmatch (XM)
Donor-specific HLA antibody testing
- Standard: qualitative (positive vs negative)
- Flow: quantitative (measures degree of antibody activity)

recipient lymphocytes + donor blood

Positive XM indicates pre-formed DSA present = ___ risk of rejection
- Deceased donor transplant is typically ___
- May be able to overcome for ___ donor transplants

HIGH
CANCELLED
living

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Allograft Rejection

Immune response causing inflammation and direct tissue ___
- Ultimately can lead to loss of graft ___
- Can occur via T-cells, B-cells, or both

destruction
function

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Risk of Rejection

highest to lowest risk

Risk increases with more ___ tissue
(more APCs transplanted with organ)

1) small bowel, lung
2) heart
3) kidneys, pancreas
4) liver

lymphoid

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Risk of Rejection

Recipient Characteristics

Age
- Immunosenescence: gradual ___ of immune system as age increases
- Higher risk of infections + malignancies, lower risk of rejection
- Can affect choice of induction (lymphocyte-depleting vs. non-depleting)

Race - African Americans
- Greater risk of rejection
- Rapid metabolizers of ___ = Much higher dose requirements
- May benefit from ___ (prolonged-release tacrolimus)

deterioration
tacrolimus
Envarsus

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Types of Allograft Rejection

T-cell Mediated Rejection (TCMR)
- Also more commonly known as ___ cellular rejection (ACR)
- Infiltration of the allograft by ___ and other inflammatory cells

Antibody Mediated Rejection (AMR)
- Evidence of acute tissue injury
- Circulating ___ (DSA) produced from plasma cells
- Immunological evidence of an ___-mediated process

acute
lymphocytes
donor-specific antibodies
antibody

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Rejection Pathophysiology

Hyperacute rejection
- Occurs within minutes to hours after transplant
- Mediated by preformed circulating ___

Acute rejection
- Occurs within days to months after transplant
- Mediated by ___

Chronic rejection
- Occurs months to years after transplant
- ___ cellular-mediated and antibody processes appear to be involved
- Progressive decline in organ function

antibodies
T-cells
both

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Goals of Immunosuppressive Therapy

Under-immunosuppression ↓ - ___
Over-immunosuppression ↑ - ___ , toxicity, malignancy

Combination therapy
- Maximize immunosuppression with overlapping/synergistic mechanisms
- Minimize ___ by using lower doses of individual agents

Rejection
Infection
side effects

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Immunosuppressive Regimens

Induction therapy
- Intense prophylactic therapy at the time of ___
- Given to lower incidence of rejection and delay use of maintenance agents
- Use depends on immunologic risk of patient

Maintenance therapy
- Long-term, chronic immunosuppression given after transplant
- Less ___ than induction and needed ___

Rejection therapy
- Most ___ therapy utilized in response to a rejection episode

transplant
potent
lifelong
intense

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Induction Agents

Polyclonal antibodies (2)

1) Rabbit antithymocyte globulin (Thymoglobulin)
2) Horse antithymocyte globulin (ATGAM)

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Induction Agents

Monoclonal antibodies (1)

Alemtuzumab (Campath-1H)

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Induction Agents

IL-2a receptor antagonists (1)

Basiliximab (Simulect)

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Induction Immunosuppression Targets

CD ___ , ___ , and ___

CD3
CD25
CD52

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Rabbit Antithymocyte Globulin

Indication: ___ and/or ___ therapy

Composed of ___ IgG against human T-lymphocytes derived from horses (ATGAM) or rabbits (Thymoglobulin)

MOA: Reduces the number of circulating ___ , which alters activation, homing, cytotoxic function
- Ultimately affects cell-mediated & humoral immunity
- T1/2~30 days; ___ ___ persisting for ~3 months

T-lymphocytes
lymphocyte depletion

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Rabbit Antithymocyte Globulin

Adverse effects
- ___ , ___ (dose limiting)
- ___ , chills (Pre-medication with ___ & ___ )
- Pruritus, erythema, rash
- Tachycardia, hypotension
- Serum sickness (rare)

Leukopenia, thrombocytopenia
fever, diphenhydramine, acetaminophen

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# Alemtuzumab (Campath-1H) Indication: **off-label** use in SOT as induction Humanized anti-CD __ monoclonal antibody - cell surface glycoprotein located on __ and __ lymphocytes, NK cells, and less densely on monocytes & macrophages Antibody-dependent cellular cytotoxicity - **Profound depletion of ___** ; to a lesser degree B cells and monocytes - Can persist for up to ~12 months AEs - Neutropenia, thrombocytopenia, pancytopenia - Fatigue, headache, dizziness, insomnia - Hypotension, supraventricular tachycardia - Rash, urticaria, pruritus - ___ -related: chills, rigors, ___ (Pre-medication with ___ and ___ )

T, B T cells infusion, diphenhydramine, acetaminophen

# Basiliximab (Simulect) Indication: induction only ___ , chimeric (murine/human) monoclonal antibody against CD __ - Bind to the α subunit of the IL-2R - Competitively inhibits ___ -mediated activation of lymphocytes - NON- ___ Dosing considerations - 20mg IVPB intraoperatively and POD4 - No pre-medications needed Well tolerated; minimal adverse effects

- Recombinant - CD25 - IL-2 - NON-lymphodepleting

# Choosing an Induction Agent - Varies by Organ! Lymphocyte ___ therapy is more commonly used - Especially for patients with high immunologic risk Basiliximab is reserved for some patient-specific factors - History of ___ - High infection risk, immunocompromised - HIV, untreated HCV - Advanced age (> ___ )

depleting malignancy 65

which one is non-depleting? a) Alemtuzumab b) Thymoglobulin c) Basiliximab

Basiliximab

which one is polyclonal? a) Alemtuzumab b) Thymoglobulin c) Basiliximab

Thymoglobulin

TH is a 58 yo AA M with ESRD 2/2 T2DM who presents for a living related kidney transplant (LRKT) from his son. He has been anuric for 2 months and has been tolerating HD MWF. Patient denies any recent fevers, chills, N/V/D/C, abdominal pain, or other complaints today. PMHx includes CKD, HTN, gout, diabetic neuropathy, and previous melanoma (treated 2010). What would be the an appropriate induction agent for this patient? - A. Alemtuzumab - B. Thymoglobulin - C. Basiliximab

Basiliximab | previous melanoma (treated 2010)

# Maintenance Agents Calcineurin Inhibitors (2)

- Cyclosporine - Tacrolimus

# Maintenance Agents Antimetabolites (3)

- Azathioprine - Mycophenolate mofetil - Mycophenolate sodium

# Maintenance Agents mTOR Inhibitors (2) | mammalian target of rapamycin

- Sirolimus - Everolimus

# Maintenance Agents Corticosteroids (3)

- Methylprednisolone - Prednisone - Dexamethasone

# Maintenance Agents T-cell Co-stimulation Blocker (1)

Belatacept

# Calcineurin Inhibitors (CNI) Cornerstone of immunosuppression - Most commonly utilized immunosuppressants - Improves survival, reduces hospitalization, reduces patient morbidity ___ (Neoral, Gengraf, Sandimmune) ___ (Prograf, Astagraf XL, Envarsus XR) MOA: - Induces immunosuppression by inhibiting ___ of T-cell activation - Inhibition of calcineurin ___ enzyme within the T-cell → prevents subsequent T-cell activation

Cyclosporine Tacrolimus signal-1 phosphatase

# CNI - Cyclosporine (CsA) Non-modified: Sandimmune - Poor and erratic bioavailability Modified microemulsion: ___ NON-modified and Modified are NOT ___ Conversion to IV typically __ : __ (e.g., 30mg IV = ~90mg PO) Therapeutic Drug Monitoring (TDM) - Intersubject ___ of CsA exposure (AUC) ranges 20-50% - Goal 12-hr trough ranges ~100-400 ng/mL

Neoral interchangeable 3:1 variability

# Cyclosporine (CsA) TDM Target trough: ___ - ___ ng/ml; depending on time post transplant, transplant type, and organ * Trough targets higher in initial post transplant period then decrease over time * Center specific Also possible to check levels 2 hours post-dose (C2) and AUC (0, 2 and 4 hour post-dose levels * More difficult clinically, not as common as troughs

- 100-400

# Tacrolimus (FK) - CNI Formulations - Immediate-Release: Prograf - Extended-Release: Astagraf XL, Envarsus XR - Potential benefits to ___ dosing: lower overall drug dose, improved adherence, less peak effects = reduced ADE, less swings/variability in trough concentrations DIFFERENT conversions for IR vs. ER - Conversion to SL typically ~2:1 (4mg PO = ~2mg SL) - Conversion to IV typically ~5:1 (2mg IV = ~10mg PO) Therapeutic Drug Monitoring (TDM) - ___ more potent than cyclosporine - Goal 12-hr trough ranges ~ __ - __ ng/mL

ER 50x 5-15

# Tacrolimus (FK) Formulations Name: ___ - IR caps/suspension - given BID Oral, sublingual, intravenous * Not a 1:1 conversion! * 2mg PO = 1mg SL = 0.33mg IV * IV: continuous infusion

Prograf

# Tacrolimus (FK) Formulations Name: ___ Extended release caps Given DAILY - Still available commercially but has fallen out of favor due to PK profile

Astagraf

# Tacrolimus (FK) Formulations Name: ___ Extended release tabs Given DAILY Not a 1:1 conversion between formulations! - 1mg total daily dose of Prograf = 0.8mg total daily dose of Envarsus

Envarsus

# Tacrolimus (FK) - TDM ___ blood concentrations - Trough ss concentration correlates well with AUC Target trough: ___ - ___ ng/ml; depending on time post transplant, transplant type, and organ - Trough targets higher in initial post transplant period then decrease over time - Center specific

- Trough - 5-15

# CNI Metabolism and Elimination - Cyclosporine (CsA) Metabolism - CYP3A4 and ___ inhibitors → ___ CsA exposure - Prone to multiple drug-drug interactions! Elimination - T 1/2 highly ___ (10-40 hr) - Prolonged in hepatic disease or disorders of biliary excretion

- P-glycoprotein, INCREASE - variable

# CNI Metabolism and Elimination - Tacrolimus (FK) Metabolism - ___ inhibitors → ___ FK exposure - Prone to multiple drug-drug interactions! Elimination - T 1/2 more ___ (12-18 hr) - Prolonged in hepatic disease or disorders of biliary excretion

- CYP3A4, INCREASE - consistent

# CNI Adverse Effects - Cyclosporine (CsA) - Nephrotoxicity - ___ (~50%) - Neurotoxicity (tremors, 12-34%) - ___ - ___ - Hyperglycemia; post-transplant diabetes mellitus [PTDM] - Electrolyte changes (↑K, ↓Mg) - ___ hyperplasia (2-16%) - ___ (21-45%)

- Hypertension - Hypercholesterolemia - Hypertriglyceridemia - Gingival - Hirsutism

# CNI Adverse Effects - Tacrolimus (FK) - Nephrotoxicity - Hypertension - ___ [Headache (64%), insomnia (64%), tremor (56%), dizziness (19%)] - ___ ; post-transplant diabetes mellitus [PTDM] (~20%) - Electrolyte changes (↑K, ↓Mg) - GI adverse reactions - ___

- Neurotoxicity - Hyperglycemia - Alopecia

# CNI Drug Interactions CYP 450 Enzyme Inducers (4) = ___ CSA/FK concentrations

↓ - Phenytoin - Carbamazepine - Phenobarbital - Rifampin

CYP 450 Enzyme Inhibitors = ___ CSA/FK concentrations

↑ - Erythromycin, clarithromycin - Azole Antifungals - Diltiazem, verapamil - Ritonavir - Grapefruit juice

# CNI Pharmacokinetics in Organ Dysfunction Liver dysfunction: alterations in CNI PK - ___ primarily eliminated by hepatic metabolism - T ½ prolonged Renal dysfunction: no change in CNI PK - Dose adjustments not necessary

Tacrolimus

LS is a 52 yo white F with ESLD 2/2 NASH cirrhosis s/p orthotopic liver transplant (OLT) 4 months ago. She was recently admitted to the hospital and diagnosed with pneumonia and oral candidiasis (thrush), for which she was prescribed antibiotics. Patient now returns to clinic for her follow-up. She notes a new fine hand tremor and her FK level is supra-therapeutic. Which of the following medications may be contributing to her elevated levels? - A. Fluconazole - B. Azithromycin - C. Levofloxacin - D. None of the above

- A. Fluconazole | oral candidiasis (thrush)

# Maintenance Immunosuppression: Antimetabolites Azathioprine (AZA) MOA: ___ analog 1) AZA converted to 6-MP in blood 2) 6-MP incorporated into nucleic acids 3) Inhibition of ___ and ___ synthesis 4) Inhibition of immune cell proliferation No routine TDM

Purine RNA, DNA

# Azathioprine (AZA) Adverse effects - Lack of specificity and potential for inhibiting replication in other highly proliferative tissues such as bone marrow and gut - ___ : abdominal pain, N/V, diarrhea, dyspepsia - ___ suppression: agranulocytosis, macrocytic anemia, leukopenia, neutropenia, thrombocytopenia - Alopecia, hepatotoxicity Drug interactions - Less common than CNIs - Allopurinol & ___ (reduce AZA by 50-75%)

- GI - bone marrow - Febuxostat

# Mycophenolic Acid (MPA) **Most commonly used adjunct agent with CNIs** - Usually in combination with ___ MOA - Inhibits the de novo pathway of ___ synthesis, ( ___ for lymphocytes) - Limits progression of activated __ and __ cells Metabolism - Immediately ___ to form free MPA, the active compound - Most of the free MPA is conjugated in the liver by glucuronyl transferase

- tacrolimus - purine, selective - T, B - hydrolyzed

# Mycophenolic Acid (MPA) Mycophenolate mofetil, MMF (CellCept) - ___ , immediate release (stomach) - Typical dose 500-1000mg PO BID Mycophenolate sodium, MPS (Myfortic) - ___ coated, delayed release (small intestine) - Typical dose 360-720mg PO BID **Therapeutically equivalent & interchangeable** but dosing requires conversion - MMF 250mg = MPS 180mg - IV:PO = 1:1 - TDM is controversial!

- Prodrug - Enteric

# Mycophenolic Acid (MPA) Adverse effects - GI: abdominal pain, N/V, diarrhea, dyspepsia - Bone marrow suppression: agranulocytosis, macrocytic anemia, leukopenia, neutropenia, thrombocytopenia FDA pregnancy category D ( ___ ) - Formal consent required for women of childbearing potential ( ___ program) - 2 forms of ___ required Drug interactions - Aluminum-/magnesium-containing antacids (decreases MPA AUC) - Cholestyramine (decreases MPA AUC) - Other ___ drugs such as ___ , ___ (additive myelosuppression) - Cyclosporine

- teratogenic - REMS - birth control - myelosuppressive - valganciclovir, sirolimus

# Maintenance Immunosuppression: mTOR Inhibitors Structure - ___ = structural analog of tacrolimus - ___ = structural analog of sirolimus Acts synergistically with other immunosuppressants - Combination with ___ and/or corticosteroids - Minimal overlapping toxicity MOA: Binds to ___ , which fuses with mTOR → inhibits T-cell ___ Metabolism: CYP ___ & ___ - **Same DDI as CNIs**

- Sirolimus - Everolimus - CNI - FKBP12, proliferation - CYP3A4, P-glycoprotein

# mTOR Inhibitors Sirolimus (SRL, Rapamune) - T ½ ~60 hours - Bioavailability is ~14% with the oral solution - Oral tablet has ~27% higher bioavailability - Daily dosing - Start at ~2mg QD - Goal trough ~5-10 ng/mL - Approved for ___ transplant rejection prophylaxis

- kidney

# mTOR Inhibitors Everolimus (EVR, Zortress) - T ½ ~30 hours - Bioavailability is ~80% - Only available as a tablet - BID dosing - Start at 0.75–1mg BID - Goal trough ~3-8 ng/mL - Approved for ___ and ___ transplant rejection prophylaxis

- kidney, liver

# mTOR Inhibitors- AE Sirolimus (SRL) - ___ - Hyper ___ and ___ - Impaired ___ healing - Mouth ___ - ___ uria - Hypertension - Hepatic artery thrombosis - Anemia (↑ incidence in combination with mycophenolate) - Interstitial pneumonitis

- edema - Hyperlipidemia, Hypertriglyceridemia - wound - ulcers - Proteinuria

# mTOR Inhibitors- AE Everolimus (EVR) - ___ - hyper ___ and ___ - Impaired ___ healing - Mouth ___ - ___ uria - Kidney arterial and venous thrombosis - Derm reactions (rash, pruritus) - Arthralgia - Diarrhea - Non-infectious pneumonitis

- Edema - Hyperlipidemia, Hypertriglyceridemia - wound - ulcers - proteinuria

# mTOR Inhibitors Limitations - Impaired ___ healing → unable to use immediately post-op - ___ : increased risk of hepatic artery thrombosis post-op - ___ : increased risk of kidney arterial and venous thrombosis post-op Adjunct agents with various roles - Replace ___ in patients with toxicity (nephrotoxicity) - In combination with CNIs to use lower levels of both drugs - Replace ___ in patients with intolerable ADE - Steroid-free protocols **Will NOT be used immediately post-transplant due to impaired wound healing**

- wound - Sirolimus - Everolimus - CNIs - mycophenolate

CA is a 47 yo Hispanic male with h/o HFrEF 2/2 ischemic cardiomyopathy s/p orthotopic heart transplant 11 months ago. He has no rejection history to date and graft function is normal (EF 70%). His immunosuppression regimen includes: tacrolimus, mycophenolate, and prednisone. Patient returns to clinic for routine follow-up with complaints of ongoing nausea. His most recent CBC comes back What potential changes could you make to his immunosuppressive regimen?

Switch mycophenolate to sirolimus

CA is a 47 yo Hispanic male with h/o HFrEF 2/2 ischemic cardiomyopathy s/p orthotopic heart transplant 11 months ago. He has no rejection history to date and graft function is normal (EF 70%). His immunosuppression regimen includes: tacrolimus, mycophenolate, and prednisone. Patient returns to clinic for routine follow-up with complaints of ongoing nausea. Given his symptoms & CBC, you decide to switch to sirolimus. Given the side effect profile of the mTOR inhibitors, what baseline labs should you also check today? What are some important side effects you would want to counsel CA on?

- Baseline lipid panel = hypercholesterolemia, hypertriglyceridemia - Baseline urine protein, urine protein-to-creatinine ratio = proteinuria - CXR, baseline PFTs = pneumonitis

# Maintenance Immunosuppression: Corticosteroids - 1st approved by the FDA in the 1950s & used for immunosuppression since the 1960s - The “original” cornerstone of immunosuppression - Corticosteroid dosage is tapered to a low dose or completely off post- transplant - Some transplant centers utilize early steroid withdrawal or steroid-free regimens MOA: - inhibits ___ production by T cells and macrophage - Blocks ___ of cytokine genes including interleukins 1, 2, 3, 5, TNF-alpha, and interferon gamma - Interferes with cell ___ , recognition, and cytotoxic effector mechanisms

- cytokine - transcription - migration

# Corticosteroids - AE ADE related to both average dose and cumulative duration of use - Varies between patients - May affect many organ systems - Range of severity - Symptoms may or may not be present

# Maintenance Immunosuppression T-cell Co-stimulation Blocker Belatacept (Nulojix®) - Relative contraindication for use in ___ transplant - Studies of belatacept in liver transplant resulted in increased graft loss & death MOA: - Blocks ___ of T-cell activation (“co-stimulation”) - Blocks the CD ___ mediated co-stimulation of T-lymphocytes by binding to CD80 and CD86 on ___ - Inhibits T lymphocyte ___ and cytokine production

- liver - signal-2 - CD28 - APCs - proliferation

# Belatacept (Nulojix) Unique administration: IV only - Variable dosing, generally 5-10mg/kg IVPB over 30 minutes on various days post-transplant - Routinely Q __ weeks at an infusion clinic = guaranteed adherence! Place in therapy - Replacement or ___ to CNI - Similar efficacy in kidney transplant recipients compared to cyclosporine - GFR higher in belatacept group up to 5 years post transplant Adverse effects - Post-transplant lymphoproliferative disorder (PTLD) - 9x-fold higher rate in those who were Epstein-Barr Virus (EBV) seronegative * Contraindicated in ___ patients - Headache, anemia, GI

- 4 - adjunct - EBV seronegative

# Considerations in Selecting Immunosuppressive Regimens Post-Transplant Triple Drug Regimen CNI + antimetavolite +/- corticosteroid

# Other Immunosuppressive Regimens Approach: CNI avoidance/minimization - Rationale: improved ___ function - Potential tradeoff: increased incidence of ___ rejection Example regimens: - ___ + Mycophenolate or Azathioprine + Corticosteroids - ___ + low-dose Tacrolimus + Corticosteroids - ___ + Mycophenolate + Corticosteroids Approach: Corticosteroid withdrawal or avoidance - Rationale: goal to decrease long-term associated toxicity - CV risk, hypertension, hyperlipidemia, glucose intolerance, weight gain, bone loss

- renal - acute - Sirolimus - Everolimus - Belatacept

# Rejection Immunosuppressive Regimens Acute Cellular Rejection (ACR) - Mild-moderate: High-dose corticosteroids - ___ 250-1000mg IV x 3-5 days Moderate-severe or steroid-resistant: T-lymphocyte depleting therapy - ___ antithymocyte globulin 1.5 mg/kg/day IV x 6-7 days - Refractory: ___ Antibody Mediated Rejection (AMR) - Steroids ± ___ ± IVIG - ___ in often performed in conjunction with medication therapy

- Methylprednisolone - Rabbit - Alemtuzumab - Rituximab - Plasmapheresis

# Rituximab (Rituxan) Indication: Off-label use in SOT - ___ protocols Anti CD ___ chimeric (murine/human) monoclonal antibody

Desensitization CD20

# Rituximab (Rituxan) - AE First dose “infusion reaction complex” - Can occur within 24 hours of the infusion - Hypoxia, ___ - ___ fibrillation, ___ shock - Infusion should be STOPPED if any of the above symptoms occur Pre-medication (30 min prior to administration) - Acetaminophen, Diphenhydramine, ___ Monitoring Parameters * ___ and ___ every 15 minutes x 1 hr; then every 30 min x 2 hrs; then every 2 hrs

- ARDS - Ventricular, Cardiogenic - Methylprednisolone - BP, HR

# Intravenous Immune Globulin (IVIG) Indication - ___ protocols in SOT - Treatment of ___ -mediated rejection Derived from the pooled human plasma of thousands of donors - Consists of intact immunoglobulin (Ig)G molecules Dosage - Dependent on indication, number of infusions, concomitant therapy - 100-2000 mg/kg (0.1-2 G/kg) given as continuous IV infusion

Desensitization antibody

# Intravenous Immune Globulin (IVIG) - AE ___ -related * Fever, chills, flushing * Pre-medicate with acetaminophen and diphenhydramine - Headache, myalgia, back pain - Hypotension Acute renal failure, renal dysfunction - ___ formulations Hemolysis, hemolytic anemia Monitoring - Vital signs should be taken prior to the start of the infusion, before any increase in the rate of the infusion, mid infusion, immediately post infusion

- Infusion - sucrose

OM is a 35 yo AA F with T1DM s/p simultaneous pancreas-kidney (SPK) transplant 2 months ago. Her current immunosuppression regimen is tacrolimus (goal 8-10 ng/mL) and mycophenolate 1000mg BID. Nadir creatinine post-transplant was 1.1 mg/dL, but has been trending up lately to a peak of 2.8 mg/dL. Your team suspects possible acute cellular rejection.

- Obtain a renal and pancreatic biopsy - Follow tacrolimus levels given concern for possible CNI-induced nephrotoxicity - Methylprednisolone 500mg x 3 days

# Opportunistic Infection Prophylaxis Potential bacteria - ___ - Toxoplasma gondii - Nocardia spp. - Listeria monocytogenes - Strongyloides spp. Agents - ___ - Atovaquone (Mepron) - Dapsone (Alvosulfon) - Pentamidine (Pentam) Duration: Institution-specific & organ-specific

- Pneumocystis carinii (PCP) or Pneumocystis jirovecci (PJP) - Sulfamethoxazole−Trimethoprim (SMX/TMP, Bactrim)

# Opportunistic Infection Prophylaxis Potential viruses - Herpes Simplex Virus (HSV) - Varicella Zoster Virus (VZV) - Epstein-Barr Virus (EBV) - ___ Agents - Acyclovir (Zovirax) = HSV, VZV - Valacyclovir (Valtrex) = HSV, VZV - Ganciclovir (Cytovene) [IV] = HSV, VZV, CMV - ___ Duration: Institution-specific & organ-specific MUST consider the viral serostatus of the ___

- Cytomegalovirus (CMV) - Valganciclovir (Valcyte) [PO] = HSV, VZV, CMV - donor

# Opportunistic Infection Prophylaxis Potential Yeasts/Molds - Select Candida spp. - Select Aspergillus spp. especially ___ transplant Agents - Nystatin (Mycostatin) [solution] - Clotrimazole (Mycelex) [troches] - Fluconazole (Diflucan) - Voriconazole (Vfend) - ___ (Noxafil)

- lung - Posaconazole

DJ is a 23 yo M with cystic fibrosis s/p bilateral orthotopic lung transplant now POD1 from his surgery. The donor CMV serostatus is positive (+). The recipient CMV serostatus is negative (−). He received basiliximab for induction. His current immunosuppression regimen is tacrolimus SL, mycophenolate mofetil IV, and methylprednisolone. He has no known drug allergies. - What more information would you want to know? - What 3 opportunistic infections would you need to cover? - What agents can you use to cover them?

- PJP = SMX/TMP (Atovaquone if sulfa allergic) - CMV = Ganciclovir IV or Valganciclovir PO - Aspergillus spp. = Posaconazole

Solid Organ Transplant Flashcards

(80 cards)