Rosenberg on Immunosuppression

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Alex Rosenberg is an Intensivist who was working in a transplant centre last year. He gave this talk on immunosupression at last year's Bedside Critical Care Conference and managed to make a fairly dry subject seem understandable and relevant. Go to www.intensivecarenetwork.com for the podcast.

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  • three forms of renal injury including: 1) an acute renal dysfunction due to vasoconstriction of the afferent arteriole, 2) an thrombotic microangiopathy that leads to thrombotic thrombocytopenic purpura and hemolytic uremic syndrome 3) chronic interstitial fibrosis and arteriolar sclerosis associated with persistent deterioration of renal function
  • 2 case series of anastomoticdehisence
  • Rosenberg on Immunosuppression

    1. 1. ImmunosuppressionAlex RosenbergClinical Fellow In TransplantationSt Vincent’s Hospital, Sydney
    2. 2. Rejection• Acute Rejection• T cell mediated• Humoral.•Chronic RejectionBronchiolitis obliterans syndrome
    3. 3. Calcineurin Inhibition• Cyclosporin A– Isolated 1979 from Tricoderma polysprum Rifai– Binds to Cyclophilin – inhibits Calcineurin.– Highly Lipid Soluble.– Monitoring best with Peak Levels.
    4. 4. • Tacrolimus.– Macrolide Antibiotic.– Isolated 1984 from Streptomyces tskubaensis.– Binds to FK-Binding protein.– Tacrolimus-FKBP complex inhibits calcineurin.– Empty stomach– Monitoring
    5. 5. Drug Interactions• Metabolized via cytochrome P-450 system.
    6. 6. Toxicities• Nephrotoxicity.• Hypertension• Hyperkalaemia• Hyperglycaemia• Hyperlipidaemia• Neurological side effects• Hirsuitism• Gingival hypertrophy.
    7. 7. Antimetabolites• Azathioprine– Pro drug: metabolized to 6-MP– Inactivated by TPMT.– Interferes with purine synthesis and so inhibitsDNA replication.– Adverse effects: myelosupression, GI symptoms– Interacts with allopurinol.
    8. 8. • Mycophenolate– Pro drug of mycophenolic acid.– Blocks inosine monophosphate dehydrogenase.– Selectively inhibits T & B lymphocyte clonalexpansion.– Side effects: Diarrhoea, marrow suppression.
    9. 9. Corticosteroids• Immunosuppressive and anti-inflammatory.• Inhibit transcription factors (IL2 / NFkB)• Down regulate expression of graft selfmolecules.• Usually lifelong.• First line treatment of acute rejection
    10. 10. Proliferation Signal Inhibitors• Sirolimus– Streptomyces hygroscopicus – 1975 in EasterIsland.– Binds to FK binding protein.– Inhibits activation of mTOR.– Prevents T and B cell proliferation– Synergistic with CNIs– Toxicities: Poor wound healing
    11. 11. Monoclonal Antibodies
    12. 12. To name a few….• Basiliximab – anti CD25.• Antithymocyte Globulin – CD 45 and multipleothers• Muromonab – anti CD3• Alemtuzumab – anti CD52• Rituximab – anti CD20• Bortezomib – proteasome inhibitor
    13. 13. 10 years post lung transplant
    14. 14. 13 years post lung transplant
    15. 15. 9 years post lung transplant
    16. 16. Thanks

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