FG4592 Ameliorates Peritoneal Dialysis-Associated Peritoneal Fibrosis
- Home Dialysis - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
- 802 Dialysis: Home Dialysis and Peritoneal Dialysis
- Luo, Qimei, Shunde Hospital of Southern Medical University, Foshan, Guangzhou, China
- Dou, Xianrui, Shunde Hospital of Southern Medical University, Foshan, Guangzhou, China
Inflammatory responses in the peritoneum contribute to peritoneal dialysis (PD)-associated peritoneal fibrosis. Previous studies showed that FG4592 (Roxadustat) suppressed inflammation in renal ischemia-reperfusion injury, alcohol-induced alcoholic liver disease. To date, FG4592 has become widely used for the treatment of anemia in patients undergoing dialysis. However, the role of FG4592 in the progression of peritoneal fibrosis has not been clarified. In this study, we used a PD rat model to investigate the effects of FG4592 on PD-associated peritoneal fibrosis.
A rat model of peritoneal fibrosis was induced via intraperitoneal injection of 4.25% PD fluid at a dose of 100mL/kg daily for 4 weeks. To investigate the effect of FG4592 on peritoneal fibrosis, rat were intraperitoneally injected with FG4592 at 1mg/kg per day. Rats were randomly divided into three groups: rats injected intraperitoneally with saline equivalent to the amount of PD fluid were defined as the control group (n=6), rats injected with 100mL/kg PD fluid were defined as the PD group (n=6) and rats injected with 100mL/kg PD fluid plus FG4592 were defined as PDF+FG4592 group (n=6). After 28 days of PD treatment, PET was performed on each rat before the rats were kills. The parietal and visceral peritoneal tissues were collected for Masson‘s thichrome staining, western blotting and real-time PCR.
Compared with the PD group, those of the PDF+FG4592 group showed increased net ultrafiltration volume. Masson’s trichrome staining showed that those of the PD group showed thickness of the submesothelial compact zone, and the histological change was accompanied by decreased peritoneal transport of glucose and sodium, and increased peritoneal transport of creatinine and albumin. In contrast, administration of FG4592 prevented the thickening of the peritoneum and improved the peritoneal transport function presenting as increased transport of glucose and sodium, and decreased transport of creatinine and albumin. Injection of 4.25% PD fluid significantly increased the mRNA levels of IL-1b, TNF-a and MCP-1 in the visceral peritoneum, and treatment with FG4592 effectively decreased their expression. Results of western blotting demonstrated that FG4592 inhibited the formation of fibronectin, collagen I and vimentin at protein levels.
FG4592 alleviates the development of peritoneal fibrosis in a rat model of PD.