title: Evaluation of gene panel mRNAs in urine samples of kidney transplant recipients as a non-invasive tool of graft function.
abstract: Non-invasive monitoring may be useful after kidney transplantation (KT), particularly for predicting acute rejection (AR). It is less clear whether chronic allograft nephropathy (CAN) is also associated with changes in urine cells. To identify non-invasive markers of allograft function in kidney transplant patients (KTP), mRNA levels of AGT, TGF-beta1, EGFR, IFN-gamma, TSP-1, and IL-10 in urine (Ur) samples were studied using QRT-PCR. Ninety-five KTP and 111 Ur samples were evaluated. Patients (Pts) were divided as, within six months (N = 31), and with more than six months post-KT (N = 64). KTP with more than six months post-KT were classified as KTP with stable kidney function (SKF) (N = 32), KTP with SKF (creatinine < 2 mg/dL) and proteinuria > 500 mg/24 h (N = 18), and KTP with biopsy proven CAN (N = 14). F-test was used to test for equality of variances between groups. IL-10 mRNA was decreased in Ur samples from KTP with less than six months post-KT (P = 0.005). For KTR groups with more than six months post-KT, AGT and EGFR mRNA were statistically different among KTP with SKF, KTP with SKF and proteinuria, and CAN Pts (P = 0.003, and P = 0.01), with KTP with SKF having higher mean expression. TSP-1 mRNA levels also were significantly different among these three groups (P = 0.04), with higher expression observed in CAN Pts. Using the random forest algorithm, AGT, EGFR, and TGF-beta1 were identified as predictors of CAN, SKF, SKF with proteinuria. A characteristic pattern of mRNA levels in the different KTP groups was observed indicating that the mRNA levels in Ur cells might reflect allograft function.
authors.affiliation: Division of Transplant, Department of Surgery, Virginia Commonwealth University, Richmond, Virginia, USA. vrmas@hsc.vcu.edu
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Mas
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Mas
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Yanek
authors.forename: Anne L
authors.initials: AL
authors.lastname: King
authors.forename: Eric M
authors.initials: EM
authors.lastname: Gibney
authors.forename: Adrian
authors.initials: A
authors.lastname: Cotterell
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fisher
authors.forename: Marc
authors.initials: M
authors.lastname: Posner
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Maluf
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics / Q000652:urine; D016207:Cytokines / Q000235:genetics / Q000652:urine; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D012333:RNA, Messenger / Q000235:genetics* / Q000652:urine*; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000235:genetics / Q000652:urine; D013997:Time Factors; D016482:Urinalysis
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D019700:Thrombospondin 1; D000808:Angiotensinogen; D066246:ErbB Receptors