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Tubulointerstitial fibrosis in patients with IgG4-related kidney disease: pathological findings on repeat renal biopsy

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Abstract

Renal parenchymal lesions in patients with IgG4-related kidney disease (IgG4-RKD) are characterized by tubulointerstitial nephritis with storiform fibrosis and infiltration by high numbers of IgG4-positive plasma cells. The aim of this study was to evaluate the clinical and pathological effects of corticosteroid therapy in patients with IgG4-RKD. Of six patients who were diagnosed with IgG4-RKD, four patients underwent re-biopsy at approximately 30–50 days after corticosteroid therapy was initiated. Based on the classification of Yamaguchi et al., the degree of tubulointerstitial fibrosis was classified before and after therapy. In addition, tubulointerstitial expression patterns of α-smooth muscle actin (α-SMA), collagen I, III, and IV protein, and connective tissue growth factor (CTGF) mRNA were examined. Histopathological findings before treatment showed α-SMA-positive myofibroblasts in the lesion, and CTGF mRNA-positive cells were found in the cellular infiltrate. Although corticosteroid therapy improved serum creatinine clinically, the stage of fibrosis advanced pathologically as evidenced by increased staining for collagen I and III. However, the number of IgG4-positive plasma cells decreased, and CTGF mRNA expression reduced. In other words, fibrosis had advanced from the time of extensive cell infiltration in patients with IgG4-RKD and inflammation was relieved by corticosteroid. A reduced number of positive CTGF mRNA expression cells in repeat biopsies indicated that the fibrosis process was terminated by corticosteroid therapy. We propose that corticosteroid therapy could terminate the pathway of active fibrosis, thereby inhibiting progression to renal dysfunction.

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Acknowledgments

This study was supported by a Grant-in-Aid for Diabetic Nephropathy and Nephrosclerosis Research and for Progressive Renal Diseases Research, Research on Intractable Disease, from the Ministry of Health, Labor and Welfare of Japan. This work was also supported by JSPS KAKENHI Grant Numbers, 23790967, 22590886, and 19590947 and by the Aichi Kidney Foundation.

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Authors and Affiliations

  1. Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan

    Haruna Arai, Hiroki Hayashi, Kazuo Takahashi, Shigehisa Koide, Waichi Sato, Midori Hasegawa & Yukio Yuzawa

  2. Yamaguchi’s Pathology Laboratory, Chiba, Japan

    Yutaka Yamaguchi

  3. Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Jan Aten

  4. Department of Renal Replacement Therapy and Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yasuhiko Ito

Authors
  1. Haruna Arai
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  2. Hiroki Hayashi
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  3. Kazuo Takahashi
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  4. Shigehisa Koide
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  5. Waichi Sato
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  6. Midori Hasegawa
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  7. Yutaka Yamaguchi
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  8. Jan Aten
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  9. Yasuhiko Ito
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  10. Yukio Yuzawa
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Corresponding authors

Correspondence to Hiroki Hayashi or Yukio Yuzawa.

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Arai, H., Hayashi, H., Takahashi, K. et al. Tubulointerstitial fibrosis in patients with IgG4-related kidney disease: pathological findings on repeat renal biopsy. Rheumatol Int 35, 1093–1101 (2015). https://doi.org/10.1007/s00296-014-3153-5

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  • DOI: https://doi.org/10.1007/s00296-014-3153-5

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