Treatment of Rejection

Question 1

Kidney TCMR Nomenclature

Answer 1

Banff IA, IB, IIA, IIB, or III

Question 2

Liver TCMR Nomenclature

Answer 2

Mild, moderate or severe rejection

Question 3

Heart TCMR Nomenclature

Answer 3

Grade 0R (no rejection), 1R (mild), 2R (moderate), 3R (severe)

Question 4

Lung TCMR Nomenclature

Answer 4

A0 (none) through A4 (severe)

Question 5

Intestine TCMR Nomenclature

Answer 5

Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe)

Question 6

Liver TCMR - When to treat

Answer 6

Moderate or severe

Question 7

Heart TCMR - When to treat

Answer 7

2R or 3R unless hemodynamic instability

Question 8

Lung TCMR - When to treat

Answer 8

A2, A3, or A4 unless symptomatic

Question 9

Kidney ABMR - Requirements for dx

Answer 9

(1) Histologic evidence on pathology, (2) C4d staining or microvascular inflammation, (3) DSA

Question 10

Liver ABMR - Requirements for dx

Answer 10

(1) Histologic evidence on pathology, (2) C4d staining, (3) DSA, (4) Exclude other causes

Question 11

Heart ABMR - Requirements for dx

Answer 11

(1) Histologic evidence on pathology, (2) Immunopathologic evidence such as C4d; clinical dysfunction and DSA are optional

Question 12

Lung ABMR - Requirements for dx

Answer 12

Requires symptoms, and 2-4 of the following:(1) Histologic evidence on pathology, (2) C4d staining, (3) DSA, (4) Exclude other causes

Question 13

Heart ABMR - Nomenclature

Answer 13

pAMR 0 = negative
pAMR 1 (H+) = histologic alone pAMR 1 (I+) = immunopathologic alone
pAMR 2 = pathologic AMR
pAMR 3 = severe pathologic AMR

Question 14

Lung ABMR - Nomenclature

Answer 14

Possible (2), probable (3) or definitive ABMR (4)

Requires symptoms, and 2-4 of the following:(1) Histologic evidence on pathology, (2) C4d staining, (3) DSA, (4) Exclude other causes

Question 15

CLAD Staging

Answer 15

(Based on FEV1)
CLAD 0: FEV1 >80% baseline
CLAD 1: 65 - 80%
CLAD 2: 50 - 65%
CLAD 3: 35 - 50%
CLAD 4: FEV1 < 35% baseline

Question 16

CLAD: possible vs probable vs definite

Answer 16

Lung allograft dysfxn: >10% decline FEV1 +/- FVC from baseline
Possible CLAD: < 3 weeks; >20% decline
Probable CLAD: 3 weeks - 3 months; >20% decline
Definite CLAD: > months; >20% decline

Question 17

CLAD phenotypes

Answer 17

1. BOS: bronchiolitis obliterans syndrome [obstructive; FEV1/FVC <0.7]
2. RAS: restrictive allograft syndrome [restrictive; TLC decline >10%]
3. Mixed

Question 18

BOS Treatment

Answer 18

1. Optimize IS (CsA –> FK)
2. Azithro 250 mg TIW
3. Fundoplication if GERD

?Montelukast

Question 19

RAS Treatment

Answer 19

Little data indicating effective treatment - antifibrotics, campath, TLI, ECP

Question 20

CAV Nomenclature

Answer 20

CAV0 = no detectable CAV
CAV1 = Mild
CAV2 = Moderate
CAV3 = Severe

Question 21

CAV Risk Factors

Answer 21

Rejection, DSA, HTN, HLD, DM, CMV infection, older donor age

Question 22

BOS Risk Factors

Answer 22

Rejection, GERD, CMV, respiratory viral infxn, PSA colonization, Aspergillus colonization or fungal PNA, increased BAL neutrophils, PGD

Question 23

RAS Risk Factors

Answer 23

Acute rejection, PSA colonization, infection, blood eosinophilia, BAL eosinophilia and neutropenia

Question 24

MOA: Rituximab

Answer 24

Anti-CD20 monoclonal antibody where CD20 is expressed on mature B cells (but not plasma cells)

= complement-dependent and antibody-dependent cytotoxicity of B cells

Question 25

Rituximab pre-med, ppx and warnings

Answer 25

1. Pre-med with APAP & Benadryl +/- steroid 2. PCP prophylaxis x6 months 3. Boxed warning for HBV reactivation

Question 26

MOA: Proteosome Inhibitors

Answer 26

Reversible inhibitor of the 26S proteasome = misfolded proteins apoptosis

Question 27

Proteosome Inhibitors: PPX

Answer 27

HSV prophylaxis

Question 28

MOA: Eculizimab

Answer 28

Monoclonal antibody that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9

Question 29

Eculizimab: Vaccines

Answer 29

Meningococcal vaccines at least 2 weeks prior | If unabl to do so - abx prophy like PCN 500 Q12, azithro 250 daily

Question 30

Tocilizumab

Answer 30

Recombinant, humanized IL-6R monoclonal antibody that binds both soluble IL-6R and membrane IL-6R IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes and fibroblasts.

Question 31

MOA: IVIG

Answer 31

Concentrated IgG antibodies purified from large pools of human plasma (other Ig present in small quantities) - Enhances antibody clearance - Neutralizing effects and blocks action of the complement & cytokines - Inhibition of T cell proliferation - B cell apoptosis - Inhibition of cytokine synthesis - Negative regulatory signals via activation of Fv gamma receptors

Question 32

MOA: Plasmapheresis

Answer 32

Remove DSA from the circulation. Not to be used alone – does not prevent antibody formation and there is rebound of circulating DSA after pheresis - Alternate day PP may allow for optimal antibody removal by giving adequate time (~48H) for re-equilibration of antibody to intravascular space from interstitium

Question 33

AlloMap: Who are candidates per ISHLT?

Answer 33

Heart txp recipients, low-risk patients, 6 months - 5 years post-txp

Question 34

AlloMap cutoff for biopsy

Answer 34

2-6 months: 30+ 6+ months: 34+ Range: 0-40

Question 35

AlloSure: Who are candidates?

Answer 35

Kidney txp 18+, at least 14 days post-txp; not twin or pregnant

Question 36

Allosure Cutoffs

Answer 36

Borderline: 0.5 TCMR: 1.0 Serial increase >61%

Question 37

Benefits of DSA monitoring

Answer 37

- Detect DSA earlier and reduce incidence of AMR | - But no diff in rates of patient or graft survival; $$$