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学科主题: 临床医学
题名:
Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker
作者: Ju, Wenjun1,2; Nair, Viji1; Smith, Shahaan1; Zhu, Li3; Shedden, Kerby2,4; Song, Peter X. K.5; Mariani, Laura H.1,6; Eichinger, Felix H.1; Berthier, Celine C.1; Randolph, Ann1; Lai, Jennifer Yi-Chun1; Zhou, Yan5; Hawkins, Jennifer J.1; Bitzer, Markus1; Sampson, Matthew G.7; Thier, Martina8; Solier, Corinne8; Duran-Pacheco, Gonzalo C.8; Duchateau-Nguyen, Guillemette8; Essioux, Laurent8; Schott, Brigitte8; Formentini, Ivan8; Magnone, Maria C.8; Bobadilla, Maria8; Cohen, Clemens D.9; Bagnasco, Serena M.10; Barisoni, Laura11; Lv, Jicheng3; Zhang, Hong3; Wang, Hai-Yan3; Brosius, Frank C.1,12; Gadegbeku, Crystal A.13; Kretzler, Matthias1,2; ERCB; C-PROBE; NEPTUNE; PKU-IgAN Consortium
刊名: SCIENCE TRANSLATIONAL MEDICINE
发表日期: 2015-12-02
DOI: 10.1126/scitranslmed.aac7071
卷: 7, 期:316
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]: Cell Biology ; Research & Experimental Medicine
关键词[WOS]: GLOMERULAR-FILTRATION-RATE ; DIABETIC-NEPHROPATHY ; GENE-EXPRESSION ; RENAL-FUNCTION ; NEPHROTIC SYNDROME ; IGA NEPHROPATHY ; NETWORK NEPTUNE ; PROGRESSION ; CKD ; EXCRETION
英文摘要:

Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of progression while in early stages of CKD. To address this challenge, a renal biopsy transcriptome-driven approach was applied to develop noninvasive prognostic biomarkers for CKD progression. Expression of intrarenal transcripts was correlated with the baseline estimated glomerular filtration rate (eGFR) in 261 patients. Proteins encoded by eGFR-associated transcripts were tested in urine for association with renal tissue injury and baseline eGFR. The ability to predict CKD progression, defined as the composite of ESKD or 40% reduction of baseline eGFR, was then determined in three independent CKD cohorts. A panel of intrarenal transcripts, including epidermal growth factor (EGF), a tubule-specific protein critical for cell differentiation and regeneration, predicted eGFR. The amount of EGF protein in urine (uEGF) showed significant correlation (P < 0.001) with intrarenal EGF mRNA, interstitial fibrosis/tubular atrophy, eGFR, and rate of eGFR loss. Prediction of the composite renal end point by age, gender, eGFR, and albuminuria was significantly (P < 0.001) improved by addition of uEGF, with an increase of the C-statistic from 0.75 to 0.87. Outcome predictions were replicated in two independent CKD cohorts. Our approach identified uEGF as an independent risk predictor of CKD progression. Addition of uEGF to standard clinical parameters improved the prediction of disease events in diverse CKD populations with a wide spectrum of causes and stages.

语种: 英语
所属项目编号: 305608 ; R01DK079912 ; P30DK081943 ; DK083912 ; P30DK020572 ; UL1RR000433 ; U54DK083912
项目资助者: Else Kroner-Fresenius Foundation ; European Consortium for High-Throughput Research in Rare Kidney Diseases (EURenOmics ; European Union) ; NIH ; Office of Rare Diseases Research ; National Center for Advancing Translational Sciences ; National Institute of Diabetes and Digestive and Kidney Diseases ; University of Michigan and NephCure Kidney International ; University of Michigan Health System ; Peking University Health Sciences Center Joint Institute for Translational and Clinical Research ; Hoffman-La Roche
WOS记录号: WOS:000366136400004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62678
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: 1.Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA
2.Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA
3.Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
4.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
5.Peking Univ, Inst Nephrol, Hosp 1, Renal Div,Dept Internal Med, Beijing 100034, Peoples R China
6.Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA
7.Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
8.Arbor Res Collaborat Hlth, Ann Arbor, MI 48104 USA
9.Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
10.Roche Pharmaceut Res & Early Dev Roche Innovat Ct, CH-4070 Basel, Switzerland
11.Univ Zurich, Inst Physiol, Div Nephrol, CH-8006 Zurich, Switzerland
12.Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
13.Temple Univ, Sch Med, Temple Clin Res Inst, Philadelphia, PA 19140 USA

Recommended Citation:
Ju, Wenjun,Nair, Viji,Smith, Shahaan,et al. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker[J]. SCIENCE TRANSLATIONAL MEDICINE,2015,7(316).
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