title: Urinary cytotoxic molecular markers for a noninvasive diagnosis in acute renal transplant rejection.
abstract: 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.
authors.affiliation: INSERM U645, Besançon, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Yannaraki
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rebibou
authors.forename: Didier
authors.initials: D
authors.lastname: Ducloux
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
authors.forename: Anne
authors.initials: A
authors.lastname: Duperrier
authors.forename: Sophie
authors.initials: S
authors.lastname: Felix
authors.forename: Gérard
authors.initials: G
authors.lastname: Rifle
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Chalopin
authors.forename: Patrick
authors.initials: P
authors.lastname: Hervé
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiberghien
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000652:urine*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology / Q000652:urine; D053222:Fas Ligand Protein; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology* / Q000652:urine; D053804:Granzymes; D006801:Humans; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000652:urine; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011183:Postoperative Complications / Q000175:diagnosis / Q000276:immunology / Q000652:urine; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000302:isolation & purification / Q000652:urine; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods* / Q000592:standards; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000235:genetics / Q000652:urine; D014184:Transplantation, Homologous; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000652:urine; D014552:Urinary Tract Infections / Q000175:diagnosis / Q000276:immunology / Q000652:urine
chemical_list: D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases