Treatment of Rejection Flashcards
Kidney TCMR Nomenclature
Banff IA, IB, IIA, IIB, or III
Liver TCMR Nomenclature
Mild, moderate or severe rejection
Heart TCMR Nomenclature
Grade 0R (no rejection), 1R (mild), 2R (moderate), 3R (severe)
Lung TCMR Nomenclature
A0 (none) through A4 (severe)
Intestine TCMR Nomenclature
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe)
Liver TCMR - When to treat
Moderate or severe
Heart TCMR - When to treat
2R or 3R unless hemodynamic instability
Lung TCMR - When to treat
A2, A3, or A4 unless symptomatic
Kidney ABMR - Requirements for dx
(1) Histologic evidence on pathology, (2) C4d staining or microvascular inflammation, (3) DSA
Liver ABMR - Requirements for dx
(1) Histologic evidence on pathology, (2) C4d staining, (3) DSA, (4) Exclude other causes
Heart ABMR - Requirements for dx
(1) Histologic evidence on pathology, (2) Immunopathologic evidence such as C4d; clinical dysfunction and DSA are optional
Lung ABMR - Requirements for dx
Requires symptoms, and 2-4 of the following:(1) Histologic evidence on pathology, (2) C4d staining, (3) DSA, (4) Exclude other causes
Heart ABMR - Nomenclature
pAMR 0 = negative pAMR 1 (H+) = histologic alone pAMR 1 (I+) = immunopathologic alone pAMR 2 = pathologic AMR pAMR 3 = severe pathologic AMR
Lung ABMR - Nomenclature
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
CLAD Staging
(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
CLAD: possible vs probable vs definite
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
CLAD phenotypes
- BOS: bronchiolitis obliterans syndrome [obstructive; FEV1/FVC <0.7]
- RAS: restrictive allograft syndrome [restrictive; TLC decline >10%]
- Mixed
BOS Treatment
- Optimize IS (CsA –> FK)
- Azithro 250 mg TIW
- Fundoplication if GERD
?Montelukast
RAS Treatment
Little data indicating effective treatment - antifibrotics, campath, TLI, ECP
CAV Nomenclature
CAV0 = no detectable CAV CAV1 = Mild CAV2 = Moderate CAV3 = Severe
CAV Risk Factors
Rejection, DSA, HTN, HLD, DM, CMV infection, older donor age
BOS Risk Factors
Rejection, GERD, CMV, respiratory viral infxn, PSA colonization, Aspergillus colonization or fungal PNA, increased BAL neutrophils, PGD
RAS Risk Factors
Acute rejection, PSA colonization, infection, blood eosinophilia, BAL eosinophilia and neutropenia
MOA: Rituximab
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
Rituximab pre-med, ppx and warnings
- Pre-med with APAP & Benadryl +/- steroid
- PCP prophylaxis x6 months
- Boxed warning for HBV reactivation
MOA: Proteosome Inhibitors
Reversible inhibitor of the 26S proteasome = misfolded proteins apoptosis
Proteosome Inhibitors: PPX
HSV prophylaxis
MOA: Eculizimab
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
Eculizimab: Vaccines
Meningococcal vaccines at least 2 weeks prior
If unabl to do so - abx prophy like PCN 500 Q12, azithro 250 daily
Tocilizumab
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.
MOA: IVIG
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
MOA: Plasmapheresis
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
AlloMap: Who are candidates per ISHLT?
Heart txp recipients, low-risk patients, 6 months - 5 years post-txp
AlloMap cutoff for biopsy
2-6 months: 30+
6+ months: 34+
Range: 0-40
AlloSure: Who are candidates?
Kidney txp 18+, at least 14 days post-txp; not twin or pregnant
Allosure Cutoffs
Borderline: 0.5
TCMR: 1.0
Serial increase >61%
Benefits of DSA monitoring
- Detect DSA earlier and reduce incidence of AMR
- But no diff in rates of patient or graft survival; $$$
