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Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker.

Publication ,  Journal Article
Ju, W; Nair, V; Smith, S; Zhu, L; Shedden, K; Song, PXK; Mariani, LH; Eichinger, FH; Berthier, CC; Randolph, A; Lai, JY-C; Zhou, Y; Bitzer, M ...
Published in: Sci Transl Med
December 2, 2015

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.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

December 2, 2015

Volume

7

Issue

316

Start / End Page

316ra193

Location

United States

Related Subject Headings

  • Transcriptome
  • Renal Insufficiency, Chronic
  • Regeneration
  • Proteins
  • Prognosis
  • Middle Aged
  • Male
  • Humans
  • Glomerular Filtration Rate
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Ju, W., Nair, V., Smith, S., Zhu, L., Shedden, K., Song, P. X. K., … ERCB, C-PROBE, NEPTUNE, and PKU-IgAN Consortium, . (2015). Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Sci Transl Med, 7(316), 316ra193. https://doi.org/10.1126/scitranslmed.aac7071
Ju, Wenjun, Viji Nair, Shahaan Smith, Li Zhu, Kerby Shedden, Peter X. K. Song, Laura H. Mariani, et al. “Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker.Sci Transl Med 7, no. 316 (December 2, 2015): 316ra193. https://doi.org/10.1126/scitranslmed.aac7071.
Ju W, Nair V, Smith S, Zhu L, Shedden K, Song PXK, et al. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Sci Transl Med. 2015 Dec 2;7(316):316ra193.
Ju, Wenjun, et al. “Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker.Sci Transl Med, vol. 7, no. 316, Dec. 2015, p. 316ra193. Pubmed, doi:10.1126/scitranslmed.aac7071.
Ju W, Nair V, Smith S, Zhu L, Shedden K, Song PXK, Mariani LH, Eichinger FH, Berthier CC, Randolph A, Lai JY-C, Zhou Y, Hawkins JJ, Bitzer M, Sampson MG, Thier M, Solier C, Duran-Pacheco GC, Duchateau-Nguyen G, Essioux L, Schott B, Formentini I, Magnone MC, Bobadilla M, Cohen CD, Bagnasco SM, Barisoni L, Lv J, Zhang H, Wang H-Y, Brosius FC, Gadegbeku CA, Kretzler M, ERCB, C-PROBE, NEPTUNE, and PKU-IgAN Consortium. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Sci Transl Med. 2015 Dec 2;7(316):316ra193.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

December 2, 2015

Volume

7

Issue

316

Start / End Page

316ra193

Location

United States

Related Subject Headings

  • Transcriptome
  • Renal Insufficiency, Chronic
  • Regeneration
  • Proteins
  • Prognosis
  • Middle Aged
  • Male
  • Humans
  • Glomerular Filtration Rate
  • Female