Own the Immunosuppressants!

Five minute teaching 002

Author: Paul Nixon
Reviewer: Chris Nickson

If you’re looking after transplant patients in the ICU, it is critical that you get the immunosuppression right. You need to OWN THE IMMUNOSUPPRESSANTS!

At The Alfred ICU we have a regular 5 minute teaching session that covers the basics of transplant immunosuppression. If you can answer the questions below, you’ll be on your way to becoming a transplant immunosuppression guru.

Q1. Why is immunosuppression used?

Required post-transplantation to prevent both

  • Acute humoral rejection (B cell antibody mediated)
  • Chronic cell mediated rejection (T cell mediated)

Q2. What types of immunosuppressant drugs are used?

Almost always 3 classes of immunosuppressive drugs are used simultaneously!

  1. Corticosteroids
  2. Anti-metabolites (e.g. azithioprine, mycophenolate)
  3. Calcineurin inhibitors (CNI) (e.g. tacrolimus, cyclosporin)

Q3. How are they given?

Loading dose prior to theatre

  • oral dose of anti-metabolite
  • oral dose of CNI (if renal function ok)

Loading dose in theatre

  • 2 x 500mg methylprednisolone IV

Maintenance doses

  • Corticosteroid
    – Tapering dose of methylprednisolone / prednisolone over 2 weeks
    – Usually remain on ~ 20mg / day
  • Mycophenolate / Azathioprine
    – IV dosing until absorbing feeds then transition to oral
    – Mycophenolate BD dosing
    – Azathioprine daily dosing
  • CNI
    – IV dosing until absorbing feeds then transition to oral
    – BD dosing

Q4. What are some other options if a CNI is contraindicated or if the patient is intolerant of CNIs?

If a CNI is contraindicated (eg. pre-existing kidney disease):

  • Basiliximab (Simulect) can be used
  • This is a monoclonal antibody that has taken over the role of ATGAM

When patients are intolerant of CNI:

  • Occasionally a proliferation inhibitor is used
  • Everolimus or sirolimus

Q5. What are the important side effects of the different immunosuppressant drugs?

All classes

  • opportunistic infections
  • common hospital acquired infections

Corticosteroids

  • hyperglycaemia
  • hypertension
  • osteoporosis (chronic use)
  • peptic ulcers

Calcineurin inhibitors – tacrolimus and cyclosporin

  • acute kidney dysfunction
  • electrolyte disturbance (low magnesium)
  • diabetes mellitus
  • hyperlipidaemia
  • neurological disturbance including seizures and posterior reversible encephalopathy syndrome (PRES)

Mycophenolate

  • gastrointestinal disturbance

Azithioprine

  • leucopaenia
  • gastrointestinal disturbance
  • hepatitis and pancreatitis

Q6. How do these immunosuppressant drugs work?

The short and highly simplified answer is that, essentially, they all block signalling from T cell to T cell and between T cells and B cells, and they  target some point in the IL-2 signalling pathway.

Immunologic mechanisms leading to graft rejection and sites of action of immunosuppressive drugs are shown in this figure from Lindenfeld et al, 2004.

References and Links

  • Lindenfeld J, Miller GG, Shakar SF, Zolty R, Lowes BD, Wolfel EE, Mestroni L, Page RL 2nd, Kobashigawa J. Drug therapy in the heart transplant recipient: part I: cardiac rejection and immunosuppressive drugs. Circulation. 2004 Dec 14;110(24):3734-40. Review. PubMed PMID: 15596559. [Free Full Text]

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.