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Decreased GM3 correlates with proteinuria in minimal change nephrotic syndrome and focal segmental glomerulosclerosis

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Abstract

Background

Glycolipids on cell membrane rafts play various roles by interacting with glycoproteins. Recently, it was reported that the glycolipid GM3 is expressed in podocytes and may play a role in podocyte protection. In this report, we describe the correlation between changes in GM3 expression in glomeruli and proteinuria in minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) patients.

Methods

We performed a case–control study of the correlation between nephrin/GM3 expression levels and proteinuria in MCNS and FSGS patients who underwent renal biopsy at our institution between 2009 and 2014. Normal renal tissue sites were used from patients who had undergone nephrectomy at our institution and gave informed consent.

Results

Both MCNS and FSGS had decreased GM3 and Nephrin expression compared with the normal (normal vs. MCNS, FSGS; all p < 0.01). Furthermore, in both MCNS and FSGS, GM3 expression was negatively correlated with proteinuria (MCNS: r = − 0.61, p < 0.01, FSGS: r = − 0.56, p < 0.05). However, nephrin expression had a trend to correlate with proteinuria in FSGS (MCNS: r = 0.19, p = 0.58, FSGS: r = − 0.48, p = 0.06). Furthermore, in a simple linear regression analysis, GM3 expression also correlated with proteinuric change after 12 months of treatment (MCNS: r = 0.40, p = 0.38, FSGS: r = 0. 68, p < 0.05).

Conclusion

We showed for the first time that decreased GM3 expression correlates with proteinuria in MCNS and FSGS patients. Further studies are needed on the podocyte-protective effects of GM3.

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Acknowledgements

We also thank Dr. Takashi. Sano for help with the diagnosis and Ms. Naoko. Ishigaki for help with the tissue staining. We also thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by JSPS KAKENHI grants (18K08249 to SN, 17K09709 and 20K08615 to NK).

Author information

Authors and Affiliations

  1. Department of Nephrology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa, 252-0374, Japan

    Shokichi Naito, Nagako Kawashima & Yasuo Takeuchi

  2. Department of Urology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa, 252-0374, Japan

    Daisuke Ishii, Tetsuo Fujita & Masatsugu Iwamura

Authors
  1. Shokichi Naito
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  2. Nagako Kawashima
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  5. Masatsugu Iwamura
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  6. Yasuo Takeuchi
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Contributions

SN conceived and designed the study, and SN and NK supervised it. SN and NK edited the manuscript. All authors contributed to the review and approval of the final manuscript.

Corresponding author

Correspondence to Shokichi Naito.

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Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

All procedures involving human participants were in accordance with ethical standards of the institution at which the studies were conducted [approval number of Kitasato University Medical Ethics Organization (KMEO): #KMEO B17-239] and with standards of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

All patients provided written informed consent for their normal kidney tissues to be obtained. Information about the intended use of biopsies from MCNS and FSGS was available on the Kitasato University Medical Ethics Organization website, allowing subjects the opportunity to opt out of the study.

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Naito, S., Kawashima, N., Ishii, D. et al. Decreased GM3 correlates with proteinuria in minimal change nephrotic syndrome and focal segmental glomerulosclerosis. Clin Exp Nephrol 26, 1078–1085 (2022). https://doi.org/10.1007/s10157-022-02249-2

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  • DOI: https://doi.org/10.1007/s10157-022-02249-2

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