title: Abbreviated AUC monitoring of cyclosporine more adequately identified patients at risk for acute rejection during induction of immunosuppressive therapy after kidney transplantation than recommended C2 concentration values.
abstract: OBJECTIVE
  Monitoring of cyclosporine (CsA) is critical during the induction of immunosuppressive therapy. Although most centers have incorporated C2 levels, our unit still uses an abbreviated AUC model which includes concentrations at C1, C2, and C6 post-dose (AUC(1-6)). The objective of this study was to compare both strategies of CsA monitoring during the first 30 days after kidney transplantation.
  
  
  METHODS
  The study included 89 recipients induced with CsA microemulsion and steroids. AUC(1-6) profiles were performed around days 3, 10, and 30 after transplantation with a target of 5500 to 6000 ng*h/mL considered therapeutic. For comparison purposes, a value of C2 >/= 1500 ng/mL was also considered therapeutic. Mean C2 and AUC(1-6) values were low dated with biopsy-proven acute rejection episodes (BPAR) during the study period.
  
  
  RESULTS
  Twenty patients received living donor kidneys and overall there were 46 females. During this period, 253 AUC(1-6) were performed including 44 (17.4%) below the therapeutic range. When the analysis included only C2, 171 (67.6%) were below the therapeutic target (P < .001). Five patients experience BPAR and only AUC(1-6) at day 10 discriminated rejectors versus nonrejectors (5645 +/- 1390 and 8221 +/- 2502, respectively; P = .008). C2 was not significantly different at any time in either group.
  
  
  CONCLUSIONS
  In this study, abbreviated AUC monitoring more adequately identified patients at risk for acute rejection than C2. Recommended C2 concentration levels need to be redefined in our patients.
authors.affiliation: Unidad de Trasplante Renal, Pontificia Universidad Católica de Chile, Santiago, Chile. pabtron@med.puc.cl
authors.forename: P
authors.initials: P
authors.lastname: Troncoso
authors.forename: A M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: A
authors.initials: A
authors.lastname: Jara
authors.forename: S
authors.initials: S
authors.lastname: Vilches
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D019540:Area Under Curve; D002102:Cadaver; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D018579:Patient Selection; D012189:Retrospective Studies; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine