Human Pathology
Volume 41, Issue 5 , Pages 672-678, May 2010

Fibrocytes are involved in the pathogenesis of human chronic kidney disease☆

  • Norihiko Sakai, MD, PhD

      Affiliations

    • Division of Blood Purification, Kanazawa University Hospital, Kanazawa 920-8641, Japan
    • ,
  • Kengo Furuichi, MD, PhD

      Affiliations

    • Division of Blood Purification, Kanazawa University Hospital, Kanazawa 920-8641, Japan
    • ,
  • Yasuyuki Shinozaki, MD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Hiroyuki Yamauchi, MD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Tadashi Toyama, MD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Shinji Kitajima, MD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Toshiya Okumura, MD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Satoshi Kokubo, MD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Motoo Kobayashi, MD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Kazuya Takasawa, MD, PhD

      Affiliations

    • Department of Internal Medicine, Public Central Hospital of Matto Ishikawa, Hakusan 924-8588, Japan
    • ,
  • Shin-ichi Takeda, MD, PhD

      Affiliations

    • Department of Internal Medicine, Kurobe Municipal Hospital, Kurobe 933-8502, Japan
    • ,
  • Mitsuhiro Yoshimura, MD, PhD

      Affiliations

    • Department of Internal Medicine, Kanazawa Medical Center, Kanazawa 920-8650, Japan
    • ,
  • Shuichi Kaneko, MD, PhD

      Affiliations

    • Faculty of Medicine, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • ,
  • Takashi Wada, MD, PhD

      Affiliations

    • Faculty of Medicine, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
    • Corresponding Author InformationCorresponding author.

Received 5 August 2009; received in revised form 30 September 2009; accepted 8 October 2009. published online 30 December 2009.

Summary 

The presence of chronic kidney disease in humans is associated with a risk of kidney function loss as well as the development of cardiovascular disease. Fibrocytes have been shown to contribute to organ fibrosis. In this study, the presence of fibrocytes was investigated immunohistochemically in kidney biopsy specimens from 100 patients with chronic kidney disease. In addition, 6 patients with thin basement membrane disease were studied as a disease control. In patients with chronic kidney disease, the infiltration of fibrocytes was observed mainly in the interstitium. The number of interstitial fibrocytes in patients with chronic kidney disease was higher than that in patients with thin basement membrane disease. The number of infiltrated fibrocytes in the interstitium correlated well with the severity of tubulointerstitial lesions, such as interstitial fibrosis, in patients with chronic kidney disease. In addition, there were significant correlations between the number of interstitial fibrocytes and the number of CD68-positive macrophages in the interstitium as well as urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was an inverse correlation between the number of interstitial fibrocytes and kidney function at the time of biopsy. Finally, the numbers of interstitial fibrocytes and macrophages as well as urinary CCL2 levels were significantly decreased during convalescence induced by glucocorticoid therapy. These results suggest that fibrocytes may be involved in the pathogenesis of chronic kidney disease through the interaction with macrophages as well as CCL2.

Keywords: CKD, Fibrocytes, Fibrosis, Chemokine

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☆ This work was supported by a Grant-in-aid from the Ministry of Education, Science, Sport and Culture of Japan and Takeda Science Foundation (T.W.) and CKD AWARD 2008 from Nippon Boehringer Ingelheim Co, Ltd, and Astellas Pharma Inc (NS).

PII: S0046-8177(09)00373-6

doi:10.1016/j.humpath.2009.10.008

Human Pathology
Volume 41, Issue 5 , Pages 672-678, May 2010

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