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Association between circulating tumor necrosis factor receptors and oral bacterium in patients receiving hemodialysis: a cross-sectional study

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Abstract

Background

High levels of tumor necrosis factor (TNF) receptors (TNFRs; TNFR1 and TNFR2), markers of inflammation, have been reported as significant predictors of mortality in hemodialysis patients. Porphyromonas gingivalis is a major pathogenic bacterium involved in periodontitis, which induces systemic inflammation. We investigated the association between the abundance of P. gingivalis in saliva and serum TNFR levels in hemodialysis patients.

Methods

A cross-sectional study was conducted on 121 hemodialysis patients visiting a clinic in the Tokyo metropolitan area. Medical interviews and examinations, comprehensive dental examinations, bacterial examinations for P. gingivalis in saliva, and measurements of circulating TNFR levels were conducted. Multiple linear regression analysis was performed to evaluate the association between the number of P. gingivalis and circulating TNFR levels.

Results

TNFR1 and TNFR2 were positively correlated with high-sensitivity C-reactive protein (hsCRP). Severe periodontitis was significantly associated with the number of P. gingivalis in saliva but not serum TNFR levels. The number of P. gingivalis was significantly associated with both TNFR1 and TNFR2 levels in sera after adjusting for age, sex, body mass index, smoking status, history of diabetes, prior cardiovascular disease events, serum levels of hsCRP and albumin, and severity of periodontitis [for TNFR1: coefficient 0.76, 95% confidence interval (CI) 0.14–1.37, p = 0.02; for TNFR2: coefficient 0.95, 95% CI 0.09–1.80, p = 0.03].

Conclusion

Circulating TNFR levels are associated with the number of P. gingivalis in saliva after adjusting for relevant clinical factors.

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Acknowledgments

The authors thank Kuniha Konuma, Naho Kobayashi, Yuka Shiheido, Makoto Kaneko, Wataru Ono, Hiroki Sato, and Rie Kawamura for their assistance with data collection.

Funding

This study was supported by a Grant from the Japan Society for the Promotion of Science (Grant-in-Aid for Research Activity Start-up 18H06304 to R.M.) and in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant Numbers 17K09711, 20K08617 to T.G.).

Author information

Authors and Affiliations

  1. Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Risako Mikami, Koji Mizutani, Takanori Matsuura, Daisuke Kido, Kohei Takeda, Yuichi Izumi & Takanori Iwata

  2. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

    Tomohito Gohda

  3. Department of Internal Medicine, Saiyu Soka Hospital, Saitama, Japan

    Hiromichi Gotoh

  4. Department of Global Health Promotion, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Yusuke Matsuyama & Takeo Fujiwara

  5. Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Kanagawa Dental University, Kanagawa, Japan

    Norio Aoyama

  6. Oral Care Perio Center, Southern TOHOKU General Hospital, Fukushima, Japan

    Yuichi Izumi

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  1. Risako Mikami
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Contributions

RM, KM, TG, HG, YI, and TI developed the concept for this study. RM, KM, TG, HG, NA, TM, DK, and KT provided substantial assistance in data collection. RM, KM, TG, YM, and TF performed statistical analyses and wrote the initial draft of the manuscript. All authors reviewed the manuscript and approved its final version.

Corresponding author

Correspondence to Tomohito Gohda.

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All the authors have declared no competing interest.

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All procedures performed in studies involving human participants were in accordance with the Research Ethics Committee of Tokyo Medical and Dental University (D2014-126).

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Supplementary material 1 (PDF 254 kb)

10157_2020_1952_MOESM2_ESM.tif

Supplementary material 2 (TIFF 93 kb) Scatter plots between serum levels of TNFRs and hsCRP. TNFR1 and hsCRP were positively correlated (Spearman’s correlation coefficient = 0.26, p = 0.005) (a) TNFR2 and hsCRP were also positively correlated (Spearman’s correlation coefficient = 0.38, p <0.001) (b).

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Mikami, R., Mizutani, K., Gohda, T. et al. Association between circulating tumor necrosis factor receptors and oral bacterium in patients receiving hemodialysis: a cross-sectional study. Clin Exp Nephrol 25, 58–65 (2021). https://doi.org/10.1007/s10157-020-01952-2

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