Urinary cytotoxic molecular markers for a noninvasive diagnosis in acute renal transplant rejection*

Authors

  • Maria Yannaraki,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
    3.  CHU Besançon, department of Nephrology, Dialysis and renal transplantation, Besançon, France
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  • Jean-Michel Rebibou,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
    3.  CHU Besançon, department of Nephrology, Dialysis and renal transplantation, Besançon, France
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  • Didier Ducloux,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
    3.  CHU Besançon, department of Nephrology, Dialysis and renal transplantation, Besançon, France
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  • Philippe Saas,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
    3.  EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, Besançon, France
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  • Anne Duperrier,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
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  • Sophie Felix,

    1.  CHU Besançon, department of pathology, Besançon, France
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  • Gérard Rifle,

    1.  CHU Dijon, department of Nephrology, Dijon, France
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  • Jean-Marc Chalopin,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
    3.  CHU Besançon, department of Nephrology, Dialysis and renal transplantation, Besançon, France
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  • Patrick Hervé,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
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  • Pierre Tiberghien,

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
    3.  EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, Besançon, France
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  • Christophe Ferrand

    1.  INSERM U645, Besançon, France
    2.  University of Franche-Comté, IFR133, Besançon, France
    3.  EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, Besançon, France
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  • *

    This work was supported in part by grants from the Foundation of transplantation (FDTSFV), BP 86, 4 rue de la Brot, 21850 Saint Appolinaire.

Christophe Ferrand, INSERM-Univ U645, IFR 133, Laboratoire de Thérapeutique Immuno-Moléculaire, EFS Bourgogne Franche-Comté, 1 Bd A. Fleming, 25020 Besançon, France.
Tel.: +33 3 8161 5615; fax: +33 3 8161 5617; e-mail: christophe.ferrand@efs.sante.fr

Summary

Perforin (P), Granzyme B (GB) and Fas-Ligand (FAS-L) are cytotoxic molecules involved in acute rejection (AR) after renal transplantation. A noninvasive diagnostic test to monitor AR and other complications could improve clinical management. We investigated the predictive and diagnostic interest of target mRNA measurements, with a quantitative PCR assay, in AR, as well as in other clinical complications recurrent in kidney transplantation. One hundred and sixty-two urine specimens from 37 allograft recipients were investigated. Clinical settings were AR, urinary tract infection (UTI), cytomegalovirus infection (CMVi) or disease (CMVd), chronic allograft nephropathy (CAN), delayed graft function (DGF) and stable graft course (controls). In the case of AR, mRNA levels of all three molecules were significantly higher than in recipients not showing any clinically evident signs of complication. Indeed, it was observed that expression levels of P, GB and Fas-L mRNA also increase in other clinical situations such as UTI, CMV and DGF. Finally, kinetic studies in three patients with AR revealed that increased P, GB and Fas-L mRNA levels could precede or were concomitant with increased serum creatinin levels. P, GB and Fas-L gene expression in urine specimens were upregulated in AR episodes but also in UTI, CMV infection and DGF. Therefore, this technique would appear to be of limited clinical value as a noninvasive method of diagnosing AR.

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