title: Urinary cell mRNA profiles and differential diagnosis of acute kidney graft dysfunction.
abstract: Noninvasive tests to differentiate the basis for acute dysfunction of the kidney allograft are preferable to invasive allograft biopsies. We measured absolute levels of 26 prespecified mRNAs in urine samples collected from kidney graft recipients at the time of for-cause biopsy for acute allograft dysfunction and investigated whether differential diagnosis of acute graft dysfunction is feasible using urinary cell mRNA profiles. We profiled 52 urine samples from 52 patients with biopsy specimens indicating acute rejection (26 acute T cell-mediated rejection and 26 acute antibody-mediated rejection) and 32 urine samples from 32 patients with acute tubular injury without acute rejection. A stepwise quadratic discriminant analysis of mRNA measures identified a linear combination of mRNAs for CD3ε, CD105, TLR4, CD14, complement factor B, and vimentin that distinguishes acute rejection from acute tubular injury; 10-fold cross-validation of the six-gene signature yielded an estimate of the area under the curve of 0.92 (95% confidence interval, 0.86 to 0.98). In a decision analysis, the six-gene signature yielded the highest net benefit across a range of reasonable threshold probabilities for biopsy. Next, among patients diagnosed with acute rejection, a similar statistical approach identified a linear combination of mRNAs for CD3ε, CD105, CD14, CD46, and 18S rRNA that distinguishes T cell-mediated rejection from antibody-mediated rejection, with a cross-validated estimate of the area under the curve of 0.81 (95% confidence interval, 0.68 to 0.93). Incorporation of these urinary cell mRNA signatures in clinical decisions may reduce the number of biopsies in patients with acute dysfunction of the kidney allograft.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Nephrology and Transplantation Department, Centre d'Investigation Clinique-BioThérapies 504 and Institut National de la Santé et de la Recherche Médicale U955 and Paris XII University, Créteil, France;
authors.forename: Marie
authors.initials: M
authors.lastname: Matignon
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and.
authors.forename: Ruchuang
authors.initials: R
authors.lastname: Ding
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and.
authors.forename: Darshana M
authors.initials: DM
authors.lastname: Dadhania
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and.
authors.forename: Franco B
authors.initials: FB
authors.lastname: Mueller
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and.
authors.forename: Choli
authors.initials: C
authors.lastname: Hartono
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and.
authors.forename: Catherine
authors.initials: C
authors.lastname: Snopkowski
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and.
authors.forename: Carol
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and.
authors.forename: John R
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sjoberg
authors.affiliation: Pathology, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York;
authors.forename: Surya V
authors.initials: SV
authors.lastname: Seshan
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Sharma
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Surgery, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors.forename: Bakr
authors.initials: B
authors.lastname: Nour
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; and.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Vickers
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and.
authors.forename: Manikkam
authors.initials: M
authors.lastname: Suthanthiran
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and mut9002@med.cornell.edu.
authors.forename: Thangamani
authors.initials: T
authors.lastname: Muthukumar
mesh_terms: D000208:Acute Disease; D003937:Diagnosis, Differential; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000652:urine*; D006801:Humans; D016030:Kidney Transplantation; D007684:Kidney Tubules; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000175:diagnosis* / Q000652:urine*; D012333:RNA, Messenger / Q000652:urine*; D014556:Urine / Q000166:cytology
chemical_list: D012333:RNA, Messenger
keywords: acute allograft rejection; mRNA; renal dysfunction