title: Allograft rejection and tubulointerstitial fibrosis in human kidney allografts: interrogation by urinary cell mRNA profiling.
abstract: Because the kidney allograft has the potential to function as an in-vivo flow cytometer and facilitate the access of immune cells and kidney parenchymal cells in to the urinary space, we hypothesized that mRNA profiling of urinary cells offers a noninvasive means of assessing the kidney allograft status. We overcame the inherent challenges of urinary cell mRNA profiling by developing pre-amplification protocols to compensate for low RNA yield from urinary cells and by developing robust protocols for absolute quantification mRNAs using RT-PCR assays. Armed with these tools, we undertook first single-center studies urinary cell mRNA profiling and then embarked on the multicenter Clinical Trials in Organ Transplantation-04 study of kidney transplant recipients. We report here our discovery and validation of diagnostic and prognostic biomarkers of acute cellular rejection and of interstitial fibrosis and tubular atrophy (IF/TA). Our urinary cell mRNA profiling studies, in addition to demonstrating the feasibility of accurate diagnosis of acute cellular rejection and IF/TA in the kidney allograft, advance mechanistic and potentially targetable biomarkers. Interventional trials, guided by urinary cell mRNA profiles, may lead to personalized immunosuppression in recipients of kidney allografts.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY; Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY. Electronic address: mut9002@med.cornell.edu.
authors.forename: Thangamani
authors.initials: T
authors.lastname: Muthukumar
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY; Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY.
authors.forename: John R
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY; Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY.
authors.forename: Darshana M
authors.initials: DM
authors.lastname: Dadhania
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Ruchuang
authors.initials: R
authors.lastname: Ding
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Sharma
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY; Department of Psychiatry and Behavioral Science, Stony Brook School of Medicine, Stony Brook, NY.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Schwartz
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY; Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY.
authors.forename: Manikkam
authors.initials: M
authors.lastname: Suthanthiran
mesh_terms: D064591:Allografts; D015415:Biomarkers; D002986:Clinical Trials as Topic; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000276:immunology; D016030:Kidney Transplantation; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger