Immunosuppression

Must constantly weigh risk of rejection against risk from immunosuppression

• No real way to measure an individual's need for immunosuppression

Corticosteroids

• Common in induction, maintenance and rescue therapies
• Prednisone most common
• May need stress dosing in emergencies
• Suppresses lymphocyte activation and promotes lymphocyte apoptosis
• Reduces production of cytokines and suppresses inflammatory response

Rabbit anti-thymocyte globulin (rATG)

• Polyclonal Ab against human T cells
• Depletes T cells
• Effectively reduces the risk of acute rejection

Basilixumab

• Alternative to rATG

Antimetabolites - inhibit lymphocyte clonal expansion

• Azathioprine (Imuran)
• Mycophenolate mofetil (Cellcept)
  • Don't need to stop if patient has another surgical condition e.g. appendicitis
  • Can be given IV
• Cyclophosphamide

Calcineurin inhibitors

• Mainstay of most multimodal immunosuppressive regimens (used in 95% of patients)
• Inhibit calcineurin, which has downstream affect of limiting T cell activation
• Cyclosporin
• Tacrolimus
  • • Especially liver transplant
    • Don't need to stop if patient has another surgical condition e.g. appendicitis
    • Needs close monitoring if giving IV
    • The IV dose is approximately one third of the oral dose
    • Target concentration varies significantly depending on patient and transplant factors. Trough concentrations are used. Steady state is reached after 3-5 days.
    • Be careful of risk of AKI if dosing is slightly wrong during acute illness - use levels if necessary

Lymphocyte-depleting agents

• Often used as induction
• Antilymphocyte globulin
• OKT3
• Anti-Il2 receptor antibodies

Inhibitors of mammalian target of rapamycin (mTOR)

• Alternative to calcineurin inhibitors
• Prevents IL-2 stimulated proliferation of T cells
• Significant impairment of wound healing
• No IV equivalents
• Everolimus
  • Stop 5 days before elective surgery
  • In emergencies, stop on admission and restart when wound heals
• Sirolimus

Induction

• Aim is to prevent acute rejection
• Give at the time of transplant

Maintenance

• Start at the time of transplant, and continue for the life of the graft
• Suppress multiple pathways with subtoxic doses of medications

Complications of immunosuppression

• Malignancy
  • Mechanism
    • Impaired immunosurveillance of neoplastic cells
    • Reduced antiviral immune activity
    • Direct mutagenic effects
  • Types
    • Skin - primarily SCC, but also BCC/melanoma
    • Kaposi's sarcoma
    • Lymphoproliferative disease (related to EBV)
    • Lymphoma
    • Cervical cancer
    • Anogenital cancer
    • TVV
    • HCC
    • Lung cancer
  • Management
    • Treat malignancy as required
    • Avoid carcinogens carefully
    • Switch immunosuppressant to mTOR, especially for skin cancers
• Infection
  • Atypical presentations, opportunistic, reactivation of chronic infections
  • C diff
  • CMV
  • Viral gastro
• Metabolic
  • Diabetes
  • Hypertension
  • Dyslipidaemia
  • CVD
  • OP/osteonecrosis

Screening in immunosuppressed patients

• Skin exam annually
• Pelvic exam and pap smear every 1-3 years
• Mammogram same as population
• HCC annual USS and AFP if cirrhosis present
• FOBT/CRC same as population