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Kidney injury induced by elevated histones in community-acquired pneumonia

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Abstract

Previous studies showed that extracellular histones could damage organs, but the role of extracellular histones in pneumonia patients with acute kidney injury (AKI) is unknown. This study aims to investigate the impact of extracellular histones on patients with community-acquired pneumonia (CAP) developed AKI. Blood samples were obtained within 24 h after admission to hospital from patients who were diagnosed with CAP. According to the discharge diagnosis, the patients were divided into 2 groups (Non-AKI and AKI). In vitro, A549 cells were treated with lipopolysaccharides (LPS) and conditioned media were collected. HK2 cells were exposed to the conditioned media or not. Cells proliferation and apoptosis of HK2 were determined. Clinically, Log2 Histones (OR 3.068; 95% CI 1.544–6.097, P = 0.001) and estimated glomerular filtration rate (eGFR) (OR 0.945; 95% CI 0.914–0.978, P = 0.001) were predictors of AKI in CAP patients. Compared to the lower histones group, patients in the higher histones group were more likely to be admitted to ICU, receive mechanical ventilation, and have a longer length of in-hospital stay. In vitro, A549 cells injured by LPS released extracellular histones, in conditioned media which significantly promoted HK2 cells apoptosis. Extracellular histones was a high risk factor for developing AKI in CAP patients and a predictor of worse short-term outcomes. We also showed that extracellular histones in conditioned media damaged HK2 cells.

Trial registration number: KY20181102-03; Date of registration: 20181102.

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Acknowledgments

We thank all the staff participating in the study.

Funding

This study was supported by the Specific Project for Technology Clinical Medicine of Jiangsu Province (BL2014015), Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX18_0428) and the Research Project of Jiangsu Provincial Commission of Health and Family Planning (BJ15004).

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Author notes

  1. Min Gao and Xin Wan contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Nanjing, 211166, Jiangsu, China

    Min Gao, Mengqing Ma, Wei Shao & Changchun Cao

  2. Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, Jiangsu, China

    Xin Wan, Binbin Pan, Yasser Gendoo & Dawei Chen

Authors
  1. Min Gao
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  2. Xin Wan
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  3. Mengqing Ma
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  5. Yasser Gendoo
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  7. Wei Shao
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  8. Changchun Cao
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Contributions

Study design: Changchun Cao, Xin Wan. Data collection: Yasser Gendoo, Dawei Chen. Data analysis: Min Gao, Mengqing Ma, Wei Shao. Cell culture: Min Gao. Manuscript writing: Min Gao, Binbin Pan.

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Correspondence to Changchun Cao.

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Gao, M., Wan, X., Ma, M. et al. Kidney injury induced by elevated histones in community-acquired pneumonia. Mol Cell Biochem 471, 155–163 (2020). https://doi.org/10.1007/s11010-020-03775-x

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