14. Transplant Flashcards
What are the important immune cells in transplant patients?
- T cells
- APCs (B-cells, macrophages, dendritic cells)
What antigen/antibody interactions are important in transplant patients?
- MHC class I and II
- cytokine release
- co-stimulatory molecules
What are the goals of immunosuppression therapy in transplants?
- prevent acute rejection while minimizing toxicity
- minimize the risk for infection
- use lowest effective dose to prolong patient and graft survival
What are the phases of immunosuppression?
- induction
- maintenance
- rejection
What are non-T cell depleting agents?
IL-2 receptor antagonists: Basiliximab
What are T-cell depleting agents?
- antithymyocyte globulin
- alemtuzumab
Maintenance immunosuppression usually consists of __ medications from ______ _____.
2-3
different classes
What are some Maintenance immunosuppressive agent combos?
- CNI + antiproliferative +/- steroids
- mTOR inhibitor + CNI + steroids
- mTOR inhibitor + antiproliferative + steroids
- Co-stimulation blocker + antiproliferative + steroids
Immunosuppressants are frequently used off-label. (T/F)
True
What is a CNI and what does it do?
- Calcineurin inhibitor
- prevents the activation of nuclear factor of T-cells
- activation normally leads to production of IL-2
What does IL-2 do?
- potent growth factor for T-cells
- activates T-cells
- produced by T-cells
What is cyclosporine and what does it do?
- calcinuerin inhibitor
- binds to cyclophilin
What is tacrolimus and what does it do?
- calcinuerin inhibitor
- binds to FKBR- 12
What are the antiproliferative agents?
mycophenolate
azathioprine
What do mTOR inhibitors do and how to they work?
- inhibits mammalian target of rapamycin
- inhibits T-cell proliferation influenced by IL-2
What are the mTOR inhibitor agents?
Sirolimus and Everolimus
Why are corticosteroids used for immunosuppression?
- broad spectrum anti-inflammatory properties
- block cytokine activation
- inhibit IL-1,2,3,6
- inhibit INF gamma
- inhibit TNF alpha
What are the corticosteroid agents?
- methylprednisolone
- prednisone
Both methylprednisolone and prednisone are converted to what?
prednisolone
Calcineurin inhibitors are metabolized hepatically primarily via which CYP enzyme? a. CYP 1A2 b. CYP 2D6 c. CYP 2E1 d.CYP 3A4
d.CYP 3A4
Which of the following medications will potentially increase serum concentrations of mTOR inhibitors?
a. Rifampin
b. Diltiazem
c. Allopurinol
d. Ferrous sulfate
b. Diltiazem
A common adverse effect associated with high dose steroid use immediately after transplant includes
a. Hyperglycemia
b. Weight loss
c. Alopecia
d. Mouth ulcers
a. Hyperglycemia
Maintenance immunosuppressive regimens following transplant typically use two to three immunosuppressive agents. (T/F)
True
Less potent immunosuppression has lead to improved graft survival but increased susceptibility to infection among SOT recipients. (T/F)
False: more potent
What are the 4 main categories of infections in SOT recipients?
- donor derived
- recipient derived
- nosocomial
- community acquired
How long is the perioperative period?
day 0 - 30
What are the major infection risks in the perioperative period?
- nosocomial infections
- surgical site infections
- line and catheter infections
- C.diff
What are the major infection risks in months 1-6?
- opportunistic infections
- community acquired infections
What are the major infection risks > 6 months?
- community acquired
- risk diminishes as immunosuppression is tapered off
What antibiotics are used to prevent pneumocystis pneumonia?
- Bactrim
- Dapsone
- inhaled pentamidine
- atovaquone
What are common perioperative period viral infections?
- donor derived (HSV, HIV, West Nile, rabies)
- reactivation (HSV)
- viral dissemination (hepatitis, pancreatitis, pneumonia)
What is the #1 cause of fever in the 1-6 month range?
viral pathogen
What is CMV?
cytomegalovirus
What solid organ transplants are most likely to get CMV?
lung and intestines
EBV requires what alteration to immunosuppression?
de-escalation
EBV can result in allograft ________.
neuropathy
What virus is associated with post-transplant lymphoproliferative disorder (PTLD)?
EBV
What virus antibody titer is take before transplant surgery?
VZV
Transplant surgery can reactivate what virus to manifest what condition?
VZV
shingles
What is the antiviral regimen for prophylaxis for low risk CMV?
acyclovir for 3 months
What is the antiviral regimen for prophylaxis for moderate/high risk CMV?
valganciclovir 900 mg for 3 – 6 months
Acyclovir prophylaxis covers what viruses?
HSV, VZV, EBV
Valganciclovir prophylaxis covers what viruses?
CMV, HSV, VZV, EBV
What is the antiviral regimen if a virus is contracted and requires treatment?
- Ganciclovir 5 mg/kg IV q12h OR
Valganciclovir 900 mg PO q12h for 14 – 21 days - followed by valganciclovir prophylaxis
What viral infections are common after 6 months post-transplant?
community acquired infections
What measures should be taken by transplant patient to avoid viral infections after 6 months post-surgery?
- annual flu shot
- avoiding sick contacts
- good hygiene
How can fungal infections be introduced in the perioperative period?
- associated with transplant surgical technique
- donor derived
What is the most common fungal infection that is associated with transplant surgical technique?
Candida albicans
What fungal infections are commonly donor derived?
- Aspergillosis
- Histoplasmosis
- Coccidioidomycosis
- Cryptococcus
Aside from surgical and donor derived infections, what other fungal infections are associated with the perioperative period?
thrush
candiduria
What fungal infections are common in the 1-6 month period post-transplant?
- Cryptococcus meningitis
- Aspergillosis (pneumonia, CNS, GI tract)
- Toxoplasmosis
- Endemic mycoses: Histoplasmosis, Blastomycosis, Coccidioidomycosis
What fungal infections are common > 6 months post-transplant?
community acquired pathogens
What antifungal prophylaxis is recommended for pancreas or liver transplants?
fluconazole
What antifungal prophylaxis is recommended for heart and lung transplants?
- itraconazole
- voriconazole
- inhaled amphotericin
What is recommended prophylaxis for mucocutaneous candida?
- clotrimazole
- nystatin
If a kidney transplant patient presents with a fever, what is the likely cause?
pylonephritis or BK virus
If a liver transplant patient presents with a fever, what is the likely cause?
anastomotic leaks
intra-abdominal abscesses
If a heart transplant patient presents with a fever, what is the likely cause?
pneumonia syndromes, sternal wound infections
If a lung transplant patient presents with a fever, what is the likely cause?
pneumonia, aspiration
