Solid Organ Transplant Flashcards
What three types of diagnostic evidence can be used to detect ABMR?
- Histologic evidence of acute tissue injury
- Microvascular injury (glomerulitis or peri-tubular capilaritis)
- Difference between acute and chronic rejection
- Evidence of current/recent antibody interaction with vascular endothelium
- C4d staining on biopsy (complement activation)
- Serologic evidence of donor specific antibodies (DSA)
- Pre-transplant DSA vs. de novo DSA

What is the time course of antibody-mediated graft damage?

What is the “triple whammy” of medication non-adherence when regarding solid organ transplants?
- Increased risk for antibody mediated rejection = Decreased graft life
- Development of DSA leads to elevated PRA and less likelihood of finding a match for next transplant
- Increase infection risk due to treatments required for AMR that develops after nonadherence
calcineurin inhibitors
- Cyclosporine (Neoral, Gengraf, Sandimmune)
- Tacrolimus (Prograf, Envarsus, Astagraf)
antiproliferative agents
- Mycophenolate mofetil/acid (Cellcept/Myfortic)
- Azathioprine (Imuran)
co-stimulatory blocker
- Belatacept (Nulojix)
inhibitors of late t-cell function
- Sirolimus (Rapamune)
- Everolimus (Zortress)
monoclonal antibodies
- Basiliximab (Simulect)
- Alemtuzumab (Campath)
polyclonal antibodies
- Antithymocyte globulin (thymoglobulin)
dosing conversion of calcineurin inhibitors
- IV:PO dosing conversion
- CYA 1:3
- TAC 1:4
- SL:PO dosing conversion
- TAC 1:2
- Tacrolimus ER (Astagraf XL) 1:1 conversioν
- Tacrolimus XR (Envarsus, Tac LCPT) 1: 0.75 – 0.8 conversion
calcineurin side effects
- Hyperglycemia
- Dyslipidemia
- Hypertension
- Hyperkalemia
- Hemolytic Uremic Syndrome
- Nephrotoxicity
- Patients may eventually require renal transplant/dialysis
- Gingival hyperplasia
- Increase infection/malignancy risk
TAC:
- Neurotoxicity
- Tremor
- Confusion/HA/Cloudiness
- Hyperglycemia (PTDM)
- Alopecia
CYA:
- Hirsutism
- Gingival hyperplasia
differences in metabolism of CYA and TAC
CYA
- Extensively metabolized by CYP3A
- Inhibits:
- CYP3A4
- P-gp
- BCRP
- OATP1B1
Tacrolimus
- Extensively metabolized by CYP3A
- Substrate of:
- CYP3A4/5
- P-gp
azole interaction with calcineurin inhibitors
- Azoles known inhibitors of CYP 3A4 and p-gp
- Concomitant administration requires dose decrease of calcineurin inhibitors
grazoprevir/elbasvir interaction with calcineurin inhibitors
- Grazoprevir (GZR)
- Substrate for OATP1B1/3 transporter, CYP3A, and P-gp
- Elbasvir (EBR)
- Substrate of CYP3A4 and P-gp
- GE is not given with CYA because of 15x increase of GE; however, TAC/GE has minimal interaction

letermovir interaction with calcineurin inhibitor
Substrate of drug metabolizing enzymes CYP3A, CYP2D6, UGT1A1, and UGT1A3, and transporters OATP1B1/3 and P-gp
Dose increase of letermovir required with CYA
statin interaction with calcineurin inhibitor
Simvastatin and atorvastatin are contraindicated with use of CYA
There are many interactions with calcineurin inhibitors. What are potential effects of these interactions?
- Increase creatinine
- Nephrotoxicity
- Decrease metabolism
- Increase metabolism
- Increase concentration of other agent
patient education for calcineurin inhibitors
- Adherence
- Medication dosed every 12 hours or 24 hours for TAC ER
- Do not take medication prior to trough draw
- Follow up with provider for labs
- DDIs
- Contact provider if develop any s/sx of infection (i.e., fever, cold/flu symptoms, urinary symptoms)
corticosteroid side effects
- Hyperglycemia
- Dyslipidemia
- Hypertension
- Insomnia
- Psychosis
- Osteoporosis
- Weight gain
- Infection
- PUD
- Cataracts
- Impaired wound healing
Findings of Astellas Corticosteroid Withdrawal Study Group
- Corticosteroid Arm
- More bone fractures + avascular necrosis
- More serious adverse effects due to DM or infection
- More ATG for acute rejection
- Higher fasting triglyceride level
- Steroid Withdrawal Arm
- Higher AR rate
- Higher incidence of hyperkalemia and neutropenia
- Similarities between 2 arms
- LDL and HDL cholesterol
- Blood pressure
- Mean weight change
- Cataracts
- Opportunistic infections
- Malignancies
- GI toxicity
- New onset diabetes (20% incidence)
patient education of corticosteroids
- Adherence
- Dosing in the AM with food
- Side effects
- Discuss importance of diet and exercise to minimize some side effects
- Contact provider if develop any s/sx of infection (i.e., fever, cold/flu symptoms, urinary symptoms)
mycophenolate MOA
- inhibits inosine monophosphatate dehydrogenase (IMPDH)
- inhibits de novo pathway of guanosine synthesis and blockade of lymphocyte proliferation (do not possess salvage pathway)
- diminishes proliferation of T and B cells
- decreases generation of CD8 cells
Significantly more effective in combination therapy than AZA
mycophenolate side effects
- Leukopenia
- GI toxicity
- Diarrhea, nausea
- Increased risk of infection/malignancy
- Embryofetal toxicity – 1st trimester
- Recommend avoiding use if planning pregnancy
- Any female of childbearing potential must use highly effective contraception 4 weeks prior to starting mycophenolate and continue contraception until 6 weeks after stopping
mycophenolate patient education
- Adherence
- Twice daily dosing. If intolerance can consider TID dosing
- Take with food (lower Cmax, but no change in AUC)
- Teratogenicity
- Contact provider if develop any s/sx of infection (i.e., fever, cold/flu symptoms, urinary symptoms)

