title: Limitations of C2 monitoring in renal transplant recipients.
abstract: BACKGROUND
  Recent developments have proposed the cyclosporin (CsA) concentration at 2 h post-dose (C(2)) as the best single time-point predictor of the extent of CsA exposure and as the optimal basis for monitoring immunosuppressive therapy in renal transplant patients. The present study sought to validate the cornerstones of the current concept of C(2) monitoring.
  
  
  METHODS
  We assessed the predictive value, dose proportionality and intrapatient variability of C(2) levels in 41 de novo renal transplant recipients treated with CsA microemulsion, steroids, mycophenolate sodium and basiliximab.
  
  
  RESULTS
  Patients with rejection and patients with CsA nephrotoxicity had lower C(2) (P = NS) and absorption (P<0.05 for toxicity), while C(0) did not show any significant difference. Receiver operating characteristic analysis did not detect discriminative C(2) values as a predictor of rejection or toxicity. In a substantial number of patients (29%) we observed poor and/or slow absorption, with C(0) >300 ng/ml and C(2) levels <800 ng/ml during the first month and a high rate of complications in these patients (18% rejection, 64% toxicity). Absorption increased over the first month post-transplant. Analysis of dose changes indicated that C(2) levels are not dose-proportional. Intrapatient variability of C(2) was as high as that of C(0).
  
  
  CONCLUSIONS
  C(2) levels do not predict rejection or toxicity. C(2) monitoring alone does not detect toxicity in poor and/or slow absorbers, who constitute a significant proportion of patients. Changes in absorption over time, high intrapatient variability and lack of dose proportionality constitute further limitations of the C(2) monitoring concept in the early post-transplant phase.
authors.affiliation: Department of Nephrology, Charité, Berlin, Germany. gunilla.einecke@ualberta.ca
authors.forename: Gunilla
authors.initials: G
authors.lastname: Einecke
authors.forename: Manuela
authors.initials: M
authors.lastname: Schütz
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mai
authors.forename: Lutz
authors.initials: L
authors.lastname: Fritsche
authors.forename: Markus
authors.initials: M
authors.lastname: Giessing
authors.forename: Petra
authors.initials: P
authors.lastname: Glander
authors.forename: Hans-H
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000097:blood*; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D007674:Kidney Diseases / Q000097:blood* / Q000139:chemically induced / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine