title: Transcriptional profiles in urine during acute rejection, bacteriuria, CMV infection and stable graft function after renal transplantation.
abstract: Acute rejection remains an important cause of renal allograft dysfunction and the need for accurate diagnosis is essential to treat transplant recipients successfully. Molecular markers in urine may serve as a diagnostic tool in acute rejection, but controversy still exists regarding the uniqueness of these biomarkers. We measured mRNA of perforin (PRF), granzyme B (GZMB) and granulysin (GNLY) normalized to cyclophilin B in urine specimens from 24 renal allograft recipients with acute rejection, 12 with bacteriuria, 11 with cytomegalovirus (CMV) infections and 17 controls with stable graft function. Measurements were performed using a real-time polymerase chain reaction assay. mRNA levels (means [95% CI]) for all three markers were significantly higher in recipients with acute rejection compared with controls: PRF (0.23 [0.12-0.42] versus 0.04 [0.02-0.07] P<0.001), GZMB (0.14 [0.09-0.23] versus 0.05 [0.03-0.08] P=0.003), GNLY (0.24 [0.14-0.41] versus 0.06 [0.03-0.11] P=0.001). GZMB and GNLY levels during acute rejection were significantly higher when compared with bacteriuria (P=0.011 and P=0.005 respectively), and PRF level during acute rejection was significantly elevated compared with CMV infection (P=0.015). No significant difference was found when comparing marker levels during bacteriuria and CMV infection to controls. Urinary mRNA levels of PRF, GZMB and GNLY are significantly elevated during acute rejection but not during bacteriuria or CMV infections when compared with recipients with stable graft function. The ability to differentiate acute rejection from bacteriuria and CMV infections was only present for some of the markers, that is why careful consideration should be given before applying this technique to clinical practice.
authors.affiliation: Research Laboratory C, Department of Nephrology, Aarhus University Hospital, Skejby, Denmark. doc.aygen@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Øzbay
authors.forename: C
authors.initials: C
authors.lastname: Tørring
authors.forename: R
authors.initials: R
authors.lastname: Olsen
authors.forename: J
authors.initials: J
authors.lastname: Carstens
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000652:urine; D001437:Bacteriuria / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000652:urine*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000652:urine*; D053804:Granzymes / Q000235:genetics / Q000652:urine; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000235:genetics / Q000652:urine; D012333:RNA, Messenger / Q000652:urine; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; C075005:GNLY protein, human; D012333:RNA, Messenger; D054353:Perforin; D053804:Granzymes