Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease

Shunsaku Nakagawa, Kumiko Nishihara, Hitomi Miyata, Haruka Shinke, Eri Tomita, Moto Kajiwara, Takeshi Matsubara, Noriyuki Iehara, Yoshinobu Igarashi, Hiroshi Yamada, Atsushi Fukatsu, Motoko Yanagita, Kazuo Matsubara, Satohiro Masuda

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

In chronic kidney disease (CKD), progressive nephron loss causes glomerular sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury. In this study, we aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage. A discovery set of renal biopsies were obtained from 48 patients with histopathologically confirmed CKD, and gene expression profiles were determined by microarray analysis. The results indicated that hepatitis A virus cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1), lipocalin 2 (also known as neutrophil gelatinase-associated lipocalin, NGAL), SRY-box 9, WAP four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in CKD. Their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury, determined by histopathological examination. The expression of these 5 genes was also increased as kidney damage progressed in a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular score using the microarray gene expression profiles of the biopsy specimens. The composite area under the receiver operating characteristics curve plotted using this molecular score showed a high accuracy for diagnosing tubulointerstitial fibrosis and tubular cell damage. The robust sensitivity of this score was confirmed in a validation set of 5 individuals with CKD. These findings identified novel molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney.

Original languageEnglish
Article numbere0136994
JournalPloS one
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 28 2015

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kidney diseases
fibrosis
Chronic Renal Insufficiency
Fibrosis
Cells
kidneys
Kidney
genetic markers
Biopsy
Microarrays
Transcriptome
Gene expression
cells
biopsy
Lipocalin 1
Wounds and Injuries
Lipocalins
Hepatitis A virus
Ureteral Obstruction
nephrons

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Nakagawa, S., Nishihara, K., Miyata, H., Shinke, H., Tomita, E., Kajiwara, M., ... Masuda, S. (2015). Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease. PloS one, 10(8), [e0136994]. https://doi.org/10.1371/journal.pone.0136994

Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease. / Nakagawa, Shunsaku; Nishihara, Kumiko; Miyata, Hitomi; Shinke, Haruka; Tomita, Eri; Kajiwara, Moto; Matsubara, Takeshi; Iehara, Noriyuki; Igarashi, Yoshinobu; Yamada, Hiroshi; Fukatsu, Atsushi; Yanagita, Motoko; Matsubara, Kazuo; Masuda, Satohiro.

In: PloS one, Vol. 10, No. 8, e0136994, 28.08.2015.

Research output: Contribution to journalArticle

Nakagawa, S, Nishihara, K, Miyata, H, Shinke, H, Tomita, E, Kajiwara, M, Matsubara, T, Iehara, N, Igarashi, Y, Yamada, H, Fukatsu, A, Yanagita, M, Matsubara, K & Masuda, S 2015, 'Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease', PloS one, vol. 10, no. 8, e0136994. https://doi.org/10.1371/journal.pone.0136994
Nakagawa, Shunsaku ; Nishihara, Kumiko ; Miyata, Hitomi ; Shinke, Haruka ; Tomita, Eri ; Kajiwara, Moto ; Matsubara, Takeshi ; Iehara, Noriyuki ; Igarashi, Yoshinobu ; Yamada, Hiroshi ; Fukatsu, Atsushi ; Yanagita, Motoko ; Matsubara, Kazuo ; Masuda, Satohiro. / Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease. In: PloS one. 2015 ; Vol. 10, No. 8.
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