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Abstract: SA-PO668

A Novel Mouse Model of Peritoneal Dialysis-Related Encapsulating Peritoneal Sclerosis

Session Information

  • Home Dialysis - II
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Sun, Juan, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Peng, Hui, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
Background

Encapsulating peritoneal sclerosis (EPS) is a severe complication in patients undergoing peritoneal dialysis (PD), with a high mortality rate. However, the insufficiency of knowledge pertaining to the etiology of EPS hampers the development of effective pharmacotherapeutic treatment, and there is a deficiency in pre-clinical models that can recapitulate the progression of the human disease. Thus, we aimed to develop an efficient and realistic mouse model of PD-associated EPS that could mimic the disease characteristics observed in humans.

Methods

Eight-week-old male C57BL/6J mice received a daily intraperitoneal injection of a combination of 4.25% PD solution and SHS (containing 0.1% chlorhexidine gluconate and 15% ethanol dissolved in saline), along with lipopolysaccharide (LPS) administration once a week. And Saline group was given intraperitoneal injection of the same volume of 0.9% saline (daily) as the control. 3 weeks later, ultrasounic and histochemical examines were used to detect abdominal changes in mice, and then RNA sequencing (RNA-seq) was performed to uncover the potential molecules and signalings in the pathogenesis of EPS.

Results

In EPS group, 76.67% mice survived and all surviving mice developed significant and diffuse peritoneal adhesion at the end of experiment. Ultrasounic and histopathological analyses demonstrated peritoneal thickening and extensive intra-abdominal adhesion. Combined with the immunohistochemical results of mice sacrificed at weeks 2 and 4, we revealed the dynamic process of adhesion formation in EPS models. Finally, the RNA-seq of peritoneal tissue showed marked fiber deposition and inflammatory cell infiltration dominated by macrophages in EPS group. These results observed in our mouse model were consistent with the characteristics of EPS patients.

Conclusion

Our novel mouse model of PD-associated EPS is efficient to replicate the key features of EPS occured on patients, and provide a promising platform to investigate the molecular pathophysiology and treatment strategy of EPS.