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Osteopontin expression and microvascular injury in cyclosporine nephrotoxicity

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Abstract

The aim of this study was to evaluate the role of osteopontin (OPN) in cyclosporine (CsA) nephrotoxicity of the human kidney. Renal biopsy samples obtained before and after 1–2 years of CsA treatment were evaluated in 18 children (2.2–13.0 years, 14 males, 4 females) diagnosed with minimal change nephrotic syndrome. The changes in tubular OPN expression between pre- and post-treatment samples were correlated with interstitial macrophage infiltration, transforming growth factor-β (TGF-β) expression, interstitial fibrosis, and microvascular density. OPN, TGF-β, CD68, and CD34 positivity were quantitatively assessed by immunohistochemical staining. Light microscopy showed that interstitial fibrosis developed in two-thirds of patients after CsA treatment. However, CD68-positive macrophages infiltrated minimally in fibrotic areas and were found in only one-third of patients. OPN expression was significantly increased in the glomerular mesangium (P=0.001) and tubules (P=0.025) after CsA treatment, whereas the number of CD34-positive peritubular capillaries decreased (P=0.022). An inverse relationship was observed between tubular OPN expression and microvascular density (r=−0.644). However, tubular OPN expression was not related to proteinuria, interstitial fibrosis, or interstitial or tubular TGF-β expression. This study indicates that increased OPN expression may be related to microvascular injury in human CsA nephrotoxicity. It also shows that OPN expression may be used as an early but non-specific marker of CsA toxicity before the manifestation of interstitial fibrosis.

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Acknowledgement

This work was supported by a grant from the Korean Society of Nephrology (Chong Kun Dang 2003) to H.J. Jeong.

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Authors and Affiliations

  1. Department of Pathology, College of Medicine, Yonsei University, Seoul, Korea

    Beom Jin Lim, Soon Won Hong & Hyeon Joo Jeong

  2. Department of Pediatrics, College of Medicine, Yonsei University, Seoul, Korea

    Pyung Kil Kim

  3. Department of Pathology, College of Medicine, Yonsei University, Shinchon-dong, Seodaemun-ku, 120–752, Seoul, Korea

    Hyeon Joo Jeong

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  1. Beom Jin Lim
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  2. Pyung Kil Kim
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Correspondence to Hyeon Joo Jeong.

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Lim, B.J., Kim, P.K., Hong, S.W. et al. Osteopontin expression and microvascular injury in cyclosporine nephrotoxicity. Pediatr Nephrol 19, 288–294 (2004). https://doi.org/10.1007/s00467-003-1386-8

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  • DOI: https://doi.org/10.1007/s00467-003-1386-8

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