title: Cyclosporine C2 levels have impact on incidence of rejection in de novo lung but not heart transplant recipients: the NOCTURNE study.
abstract: BACKGROUND
  Cyclosporine (CsA) absorption varies early after transplantation and can be accurately assessed by the area under the absorption curve (AUC). The 2-hour post-dose (C2) level of CsA in whole blood is reported to be a useful surrogate marker of CsA AUC in kidney and liver transplant monitoring, but should be further explored in thoracic organ recipients.
  
  
  METHODS
  In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by C0 and blood was collected for analysis of C2 retrospectively. Abbreviated AUC (AUC(0-4)) was measured at 7 days and 3 months. Primary outcome was C2 relation to the frequency of acute cellular rejection (ACR) needing treatment and possible decline in measured glomerular filtration rate (mGFR). Recipients were divided into lower, middle and upper third C2 groups based on 2-week post-operative values (tertiles T1 to T3).
  
  
  RESULTS
  C2 was the most robust substitute for AUC(0-4) in the group of patients studied. For lung, but not heart, recipients there were differences in mean number of ACRs (p = 0.05), incidence of any rejections (p = 0.04), mean number of any rejections (p = 0.001) and time to first rejection (p = 0.03) between T1 and T3. C2 did not predict reduction in mGFR.
  
  
  CONCLUSIONS
  C2 is a sensitive predictor for ACR in lung, but not heart, recipients, C2 was not predictive of a decline in mGFR. This study suggests that management of lung recipients by C2 may diminish the number of ACRs.
authors.affiliation: Department of Cardiology, Section of Heart and Lung Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. martin.iversen@dadlnet.dk
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
authors.forename: Folke
authors.initials: F
authors.lastname: Nilsson
authors.forename: Jorma
authors.initials: J
authors.lastname: Sipponen
authors.forename: Hans
authors.initials: H
authors.lastname: Eiskjaer
authors.forename: Lena
authors.initials: L
authors.lastname: Mared
authors.forename: Stein
authors.initials: S
authors.lastname: Bergan
authors.forename: Ulla
authors.initials: U
authors.lastname: Nyström
authors.forename: Hans E
authors.initials: HE
authors.lastname: Fagertun
authors.forename: Dag
authors.initials: D
authors.lastname: Solbu
authors.forename: Svein
authors.initials: S
authors.lastname: Simonsen
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000601:surgery; D003324:Coronary Artery Disease / Q000601:surgery; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000601:surgery; D004646:Emphysema / Q000601:surgery; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016040:Lung Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000601:surgery
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine