title: Urinary cell mRNA profiles predictive of human kidney allograft status.
abstract: Kidney allograft status is currently characterized using the invasive percutaneous needle core biopsy procedure. The procedure has become safer over the years, but challenges and complications still exist including sampling error, interobserver variability, bleeding, arteriovenous fistula, graft loss, and even death. Because the most common type of acute rejection is distinguished by inflammatory cells exiting the intravascular compartment and gaining access to the renal tubular space, we reasoned that a kidney allograft may function as an in vivo flow cytometer and sort cells involved in rejection into urine. To test this idea, we developed quantitative polymerase chain reaction (PCR) assays for absolute quantification of mRNA and pre-amplification protocols to overcome the low RNA yield from urine. Here, we review our single center urinary cell mRNA profiling studies that led to the multicenter Clinical Trials in Organ Transplantation (CTOT-04) study and the discovery and validation of a 3-gene signature of 18S rRNA-normalized measures of CD3ε mRNA and IP-10 mRNA and 18S rRNA that is diagnostic and predictive of acute cellular rejection in the kidney allograft. We also review our development of a 4-gene signature of mRNAs for vimentin, NKCC2, E-cadherin, and 18S rRNA diagnostic of interstitial fibrosis/tubular atrophy (IF/TA).
authors: Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA; Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA.
authors: John R
authors: JR
authors: Lee
authors: Thangamani
authors: T
authors: Muthukumar
authors: Darshana
authors: D
authors: Dadhania
authors: Ruchuang
authors: R
authors: Ding
authors: Vijay K
authors: VK
authors: Sharma
authors: Joseph E
authors: JE
authors: Schwartz
authors: Manikkam
authors: M
authors: Suthanthiran
mesh_terms: D064591:Allografts; D001706:Biopsy; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D006084:Graft Rejection / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000652:urine*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000652:urine*; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger
keywords: PCR; acute cellular rejection; interstitial fibrosis; kidney transplantation; urinary cell mRNA profiling