title: Advantages of C2 monitoring to avoid acute rejection in pediatric heart transplant recipients.
abstract: BACKGROUND
  Inadequate cyclosporine (CsA) blood levels are a major risk factor for acute rejection in transplant recipients. The CsA trough level (C0 level) measured just before the next dose is commonly used to adjust the oral dosage. However, the 2-hour post-CsA dose concentration (C2 level) is favored as the best single-point correlate of CsA area-under-the-curve concentration and may better reflect the immunosuppressive effect of CsA. Because an adequate C2 level has not yet been defined, this study was performed to assess the value of C2 monitoring for the prevention of acute rejection and to define target levels in pediatric heart transplant recipients.
  
  
  METHODS
  C2 levels were assessed in 50 pediatric heart transplant patients with oral CsA therapy and compared with trough C0 levels using full blood sampling, mass spectrometry and a blinded analysis. Acute graft rejection was detected using intramyocardial electrocardiogram (IMEG) and serial conventional and tissue Doppler echocardiography (TDE). Rejection was confirmed or excluded by endomyocardial biopsy.
  
  
  RESULTS
  C2 and not C0 levels were significantly reduced in patients with acute graft rejection (ISHLT Grade > or =2). Patients with a C2 level <600 ng/ml had a significantly higher risk of developing acute rejection (100% sensitivity and 82% specificity). Patients with impaired CsA absorption were identified with C2 monitoring and switched to another calcineurin inhibitor.
  
  
  CONCLUSIONS
  Monitoring of the C2 rather than the C0 level better reflects immunosuppressive efficiency and identifies patients at increased risk of acute rejection. A C2 level of >600 ng/ml should be the target to prevent acute rejection.
authors.affiliation: Department of Congenital Heart Defects/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany. sschubert@dhzb.de
authors.forename: S
authors.initials: S
authors.lastname: Schubert
authors.forename: H
authors.initials: H
authors.lastname: Abdul-Khaliq
authors.forename: H B
authors.initials: HB
authors.lastname: Lehmkuhl
authors.forename: M
authors.initials: M
authors.lastname: Hübler
authors.forename: M Y
authors.initials: MY
authors.lastname: Abd El Rahman
authors.forename: O
authors.initials: O
authors.lastname: Miera
authors.forename: P
authors.initials: P
authors.lastname: Ewert
authors.forename: Y
authors.initials: Y
authors.lastname: Weng
authors.forename: H
authors.initials: H
authors.lastname: Wei
authors.forename: B
authors.initials: B
authors.lastname: Krüdewagen
authors.forename: R
authors.initials: R
authors.lastname: Hetzer
authors.forename: F
authors.initials: F
authors.lastname: Berger
mesh_terms: D000293:Adolescent; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008991:Monitoring, Physiologic; D020551:Pulse Therapy, Drug; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008775:Methylprednisolone