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Abstract: TH-PO781

Association of Minimal Change Nephrotic Syndrome with Mitochondrial Dysfunction in a Rat Model

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Fujii, Yuko, Osaka Ika Yakka Daigaku, Takatsuki, Osaka, Japan
  • Matsumura, Hideki, Osaka Ika Yakka Daigaku, Takatsuki, Osaka, Japan
  • Tanaka, Tomoko, Osaka Ika Yakka Daigaku, Takatsuki, Osaka, Japan
  • Yamazaki, Satoshi, Osaka Ika Yakka Daigaku, Takatsuki, Osaka, Japan
  • Shirasu, Akihiko, Shiritsu Hirakata Byoin, Hirakata, Osaka, Japan
  • Nakakura, Hyogo, Osaka Ika Yakka Daigaku, Takatsuki, Osaka, Japan
  • Ashida, Akira, Osaka Ika Yakka Daigaku, Takatsuki, Osaka, Japan
Background

In recent years, it has been reported that mitochondrial dysfunction is associated with various renal diseases. However, the relationship between minimal-change nephrotic syndrome (MCNS) and mitochondrial dysfunction remains unclear. Here, using a rat model of MCNS, we examined changes in glomerular mitochondrial damage in response to increased urinary protein.

Methods

To prepare this MCNS model, male Wistar rats aged 6 weeks (n=18) each received a subcutaneous injection of 50 mg/kg puromycin aminonucleoside on day 1 and were euthanatized on days 4, 7, and 10 (n=6, respectively). Whole-day urine samples were collected from the rats on the day before euthanasia, and glomerulus and plasma samples were taken on days 4, 7, and 10 for measurement of protein, creatinine, markers of lipid peroxidation, and mitochondrial DNA content. The experimental protocol, including ethical aspects, was approved by the Osaka Medical and Pharmaceutical University Animal Care and Use Committee (approval number: 21096-A).

Results

Daily urinary protein excretion showed a gradual increase on days 3, 6, and 9 (median 18.1, 95.8, 279.1; interquartile range (IQR) 10.3-23.2, 74.3-103.0, 181.0-366.3 mg/dL, respectively; p=0.0006). The levels of plasma 4-hydroxynonenal were significantly lower on days 4 and 7 than on day 10 (median 0.73, 1.06, 3.29; IQR 0.48-1.12, 0.87-1.23, and 2.65-4.26 mg/mL; p=0.002). From day 4 to day 10, mitochondrial DNA levels decreased gradually (median 3278, 2867, 2369; IQR 3,200-3,360, 2,530-3,090, 2,068-2,937 pg/mL; p=0.01). There was a strong negative correlation between the amount of daily proteinuria and glomerular mitochondrial DNA content (r= -0.718, p= 0.008). Furthermore, glomerular mitochondrial damage was studied using transmission electron microscopy.

Conclusion

In this MCNS rat model, urinary protein excretion increased as glomerular mitochondrial dysfunction worsened. This suggests that glomerular mitochondrial dysfunction may be closely related to the pathogenesis of MCNS.

Funding

  • Government Support – Non-U.S.