Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: Insights from the mycophenolate steroid-sparing trial

E. Gotti, N. Perico, F. Gaspari, D. Cattaneo, M. D. Lesti, P. Ruggenenti, G. Segoloni, M. Salvadori, P. Rigotti, U. Valente, D. Donati, S. Sandrini, S. Federico, V. Sparacino, G. Mourad, J. L. Bosmans, B. D. Dimitrov, B. E. Iordache, G. Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C 0) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C2) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C0 levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C2 levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.

Original languageEnglish
Pages (from-to)2037-2040
Number of pages4
JournalTransplantation Proceedings
Volume37
Issue number5
DOIs
Publication statusPublished - Jun 2005

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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