title: Dangerous drug interactions leading to hemolytic uremic syndrome following lung transplantation.
abstract: BACKGROUND
  To report our experience of a rather uncommon drug interaction, resulting in hemolytic uremic syndrome (HUS).
  
  
  METHODS
  Two consecutive cases of hemolytic uremic syndrome were diagnosed in our service. In both patients the use of macrolides in patients taking Tacrolimus, resulted in high levels of Tacrolimus.
  
  
  RESULTS
  The first patient was a 48 years old female with Bilateral emphysema. She underwent Single Sequential Lung Transplantation. She developed reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51). The patient remained well up till 5 months later; Erythromycin commenced for chest infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She was treated with plasmapheresis successfully. The second case was a 57 years old female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed 1 year later and she switched to Tacrolimus. She was admitted to her local Hospital two and a half years later with right middle lobe consolidation. The patient commenced on amoxicillin and clarithromycin. Worsening renal indices, high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS diagnosed & treated with plasmapheresis.
  
  
  CONCLUSIONS
  There are 21 cases of HUS following lung transplantation in the literature that may have been induced by high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus lead to high levels. Mechanism of action could be glomeruloconstrictor effect with reduced GFR increased production of Endothelin-1 and increased Platelet aggregation.
authors.affiliation: Cardiothoracic Department, Royal Victoria Hospital, Grosvernor Rd, Belfast, BT12 6BA, Nothern Ireland. hparissis@yahoo.co.uk
authors.forename: Haralabos
authors.initials: H
authors.lastname: Parissis
authors.forename: Kate
authors.initials: K
authors.lastname: Gould
authors.forename: John
authors.initials: J
authors.lastname: Dark
mesh_terms: D004347:Drug Interactions; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced / Q000209:etiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology; D016040:Lung Transplantation; D018942:Macrolides / Q000009:adverse effects* / Q000494:pharmacology; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000601:surgery*; D016559:Tacrolimus / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D018942:Macrolides; D016559:Tacrolimus
references.citation: J Heart Lung Transplant. 2004 May;23(5 Suppl):S202-6
references.pmid: 15093806
references.citation: Transplant Proc. 2003 Mar;35(2):627-8
references.pmid: 12644073
references.citation: Transplant Proc. 2009 Jun;41(5):1821-4
references.pmid: 19545736
references.citation: Transpl Int. 1996;9(1):68-75
references.pmid: 8748414
references.citation: Drugs. 2003;63(12):1247-97
references.pmid: 12790696
references.citation: J Heart Lung Transplant. 2005 Feb;24(2):119-30
references.pmid: 15701425
references.citation: J Heart Lung Transplant. 1999 Oct;18(10):1024-6
references.pmid: 10561115
references.citation: Best Pract Res Clin Haematol. 2009 Dec;22(4):567-76
references.pmid: 19959109
references.citation: Transplantation. 1999 Feb 27;67(4):539-44
references.pmid: 10071024
references.citation: Am J Kidney Dis. 2000 Oct;36(4):844-50
references.pmid: 11007689
references.citation: J Nephrol. 2003 Jul-Aug;16(4):580-5
references.pmid: 14696762
references.citation: Transplant Proc. 1991 Dec;23(6):3156-7
references.pmid: 1721390
references.citation: J Heart Lung Transplant. 1993 May-Jun;12(3):440-4
references.pmid: 8329415
references.citation: Egypt J Immunol. 2006;13(2):95-9
references.pmid: 18689275
references.citation: Am J Nephrol. 2000 Sep-Oct;20(5):418-20
references.pmid: 11093002