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Association of apoptosis inhibitor of macrophage (AIM) expression with urinary protein and kidney dysfunction

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Abstract

Background

Apoptosis inhibitor of macrophage (AIM) expressed on macrophages prolongs inflammation by protecting macrophages from apoptosis. Most circulating AIM co-exists with immunoglobulin M (IgM). AIM’s pathophysiological role in relation to IgM remains unclear. Here we evaluated the glomerular expression/deposition of AIM and IgM in the kidney using immunohistochemistry and its associations with clinical manifestations in 43 patients with biopsy-confirmed kidney diseases.

Methods

Kidney biopsy tissue from all patients was immunostained for AIM and IgM. Staining patterns and percent stained areas within the glomeruli were determined. Cells expressing AIM were identified by co-staining with macrophage and endothelial cell surface markers. Correlations between staining results and clinical parameters were evaluated using univariate and multivariate analyses.

Results

AIM was deposited in various areas, such as mesangial and capillary area. A part of AIM expression was localized to CD68-positive macrophages in the glomerulus. Amount of glomerular expression was positively correlated with urinary protein in patients with severe proteinuria (urinary protein ≥0.5 g/day) and kidney dysfunction [estimated glomerular filtration ratio (eGFR) <60 ml/min/1.73 m2]. Urinary protein was higher in patients exhibiting overlapping glomerular expression of AIM and IgM. Annual eGFR decline rate negatively correlated with AIM-positive area. AIM-positive area and initial serum creatinine were independently associated with decreased kidney function.

Conclusion

AIM expression in the kidney was associated with urinary protein and decline in kidney function. Co-expression with IgM appeared to exacerbate AIM’s deleterious effects on kidney function. Combined glomerular AIM and IgM expression is a candidate prognostic index for kidney disease.

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Authors and Affiliations

  1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan

    Megumi Oshima, Yasunori Iwata, Kengo Furuichi, Norihiko Sakai, Miho Shimizu, Akinori Hara, Shinji Kitajima, Tadashi Toyama, Yasuyuki Shinozaki, Akihiro Sagara, Eri Umeda & Takashi Wada

  2. Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan

    Megumi Oshima, Yasunori Iwata, Kengo Furuichi, Norihiko Sakai, Miho Shimizu, Akinori Hara, Shinji Kitajima, Tadashi Toyama, Yasuyuki Shinozaki, Akihiro Sagara & Shuichi Kaneko

  3. Division of Infection Control, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan

    Yasunori Iwata

  4. Laboratory of Molecular Biomedicine for Pathogenesis, Faculty of Medicine, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo, Japan

    Satoko Arai & Toru Miyazaki

  5. Department of Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan

    Takashi Wada

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  1. Megumi Oshima
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  2. Yasunori Iwata
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  14. Toru Miyazaki
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  15. Takashi Wada
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Corresponding author

Correspondence to Yasunori Iwata.

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Oshima, M., Iwata, Y., Furuichi, K. et al. Association of apoptosis inhibitor of macrophage (AIM) expression with urinary protein and kidney dysfunction. Clin Exp Nephrol 21, 35–42 (2017). https://doi.org/10.1007/s10157-016-1240-5

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  • DOI: https://doi.org/10.1007/s10157-016-1240-5

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