Transplant medicine Flashcards
Hyperacute transplant rejection
a) Presentation
b) Immunology
c) More common in first or second transplant?
d) Microscopy
a) - Immediate (minutes) - surgeon notices graft turning white during the operation
- Leads to massive capillary thrombosis and failure of vascularisation of the graft
b) - Caused by recipient sensitised IgG antibodies
- Type 2 hypersensitivity reaction
c) Second
d) Thrombosis, neutrophil infiltration
Acute transplant rejection
a) Timeframe
b) Immunology
c) Presentation
d) Microscopy
e) How should it be investigated if suspected?
f) Treatment
a) Weeks-Months
b) T-cell mediated
- Type 4 hypersensitivity reaction
c) - Usually asymptomatic, but may have vague symptoms of tiredness, myalgia, arthralgia, sometimes fever/pain at transplant site, etc.
- Reducing renal function
d) Vascular endotheliiitis
e) - Exclude sepsis
- Check tacrolimus levels
- Ultrasound of transplanted kidney
- Further imaging and transplant biopsy if needed
f) Anti- T cell antibodies
Steroids
Chronic transplant rejection
a) Timeframe
b) Immunology
c) Presentation
d) Microscopy
e) Treatment
a) Years
b) Two subtypes:
- Chronic antibody-mediated rejection (type 2 HSR)
- Chronic T-cell mediated rejection (type 4 HSR)
c) Vague symptoms
- Reducing renal function
d) B-cell or T-cell infiltrates, or both
e) - Prevention the best method
- Steroids, IVIG etc.
Ciclosporin
a) Side effects
b) Interactions causing toxicity (also for tacrolimus)
a) - Gingival hyperplasia, hirsutism, paraesthesia, headache, arthralgia, gout, eye discomfort/inflammation
b) CYP450 3A4 inhibitors:
- Fluconazole, macrolides, amiodarone, verapamil, diltiazem
CMV infection
a) When it occurs?
b) Presentation
c) Treatment
d) CMV donor/recipient negative/positive - explain significance
a) Usually in the 6 weeks post-transplant
b) Fever, pain at transplant site, abnormal LFTs, lympadenopathy, reduced renal function
c) IV ganciclovir - 14 days (or up to 200 days if CMV negative recipient with CMV positive donor)
EBV infection in transplant patients
a) Time of onset
b) Presentation
c)
a) Usually 6 months post-transplant (later than CMV)
b) Post-transplant lymphoproliferative disease (PTLD) - diffuse B-cell hyperplasia or polymorphic B-cell lymphoma
Hepatitis infection in transplant patients
a) Time of onset
b) When should transplant patients receive Hep B vaccine?
a) Usually first 1-2 weeks
b) Before transplant
Toxoplasma infection
a) - Pneumonitis
- Choroidoretinitis
- Encephalitis
Vaccines for transplant patients
- which should be avoided
Live vaccines
- MMR
- Nasal influenza (flu injection not live so OK after 6 months, and recommended yearly)
- Chickenpox/shingles
- Yellow fever
- Typhoid
- Oral polio
Graft rejection
a) Investigations
b) Differentials
a) - Renal profile
- Graft US
- Viral screen - including CMV, BK, JC, etc.
- Renal biopsy is the definitive investigation
b) - CNI toxicity*
- BK virus associated nephropathy
- Recurrence of pre-existing renal disease
- De novo renal disease
*CNI toxicity:
- Ciclosporin and tacrolimus can cause both an acute and a chronic renal injury, generally due to reduced renal perfusion
- Risk is increased by higher doses, concomitant use of nephrotoxic drugs, use of CYP3A/5 inhibitors (macrolides, ketoconazole, ciprofloxacin, verapamil, diltiazem), older age of transplant kidney
- Treatment generally by reducing CIN doses and replacing with a different immunosuppressant
Tacrolimus
a) brand names
b) therapeutic range
c) side effects (PROGRAF)
a) Prograf, Advagraf, Adoport
b) 3-12
c) Peripheral neuropathy, tremor
Renal dysfunction, low phos, low Mg
Opportunistic infection
GI upset (N&V, constipation, diarrhoea)
RTA type 4, risk of diabetes
Anaemia
Fluid around heart (pericardial effusion)
General causes of graft dysfunction
a) Acute (day 0 to 4 months)
b) Later (4 months+)
c) Median transplanted kidney survival
a) - Graft rejection
- Ischaemic injury, renal artery thrombosis
- Anastamotic dysfunction e.g. ureteric obstruction
- Infection - bacterial (UTI), CMV
- Ciclosporin/tacrolimus toxicity
b) - Chronic allograft nephropathy
- Recurrent primary disease (e.g. glomerulonephritis)
- Ciclosporin/tacrolimus toxicity
- Infection - JC and BK virus
- Transplant RAS or microvascular complications
- Obstruction
c) 13 years
