Kidney Week

Abstract: FR-PO1102

Dextrose- or Icodextrin-Based Peritoneal Dialysis in Mice Increases Extra-Domain A-Spliced Variant of Fibronectin (EDA FN) and Induces Peritoneal Inflammation and Fibrosis

Session Information

• Home Dialysis: Modalities, Barriers, Utilization, and Clinical Outcomes
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

• Yung, Susan, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Susan Yung, PhD

• Ullah, Sami, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Sami Ullah, MPH

• Chu, David H T, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

David H T Chu

• Wong, Cheuk Yin, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Cheuk Yin Wong, PhD

• Chan, Tak Mao Daniel, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Tak Mao Daniel Chan, MD, FASN

Background

Long-term treatment with peritoneal dialysis (PD) is dependent on the structural and functional integrity of the peritoneum. We previously demonstrated that EDA FN contributed to peritoneal inflammation and fibrosis. This study investigated changes in transcriptomic profiling and molecular pathways in wild-type (WT) and EDA-FN knockout (KO) mice that received PD with dextrose-based Dianeal^TM (Di) or icodextrin-based Extraneal^TM (Ex) PD fluids.

Methods

Male WT and EDA FN KO mice were randomized to receive saline, 4.25% Di, or Ex for 20 weeks by intra-peritoneal injection twice daily for 20 weeks. Parietal peritoneum was harvested to investigate histopathology. Total RNA from peritoneal membrane specimens was extracted and subjected to bulk RNA-sequencing. Enrichment analyses were conducted for GO category genes and KEGG pathways.

Results

EDA FN expression was increased in both Di- and Ex-treated WT mice, by 5.12-fold and 3.02-fold respectively, compared with saline-treated WT mice (p<0.05, saline vs Di or Ex; p=NS, Di vs Ex). Increased EDA FN expression was accompanied by submesothelial thickening, increased macrophage infiltration, increased mediators of inflammation, epithelial-to-mesenchymal transition (EMT) and fibrosis (p<0.05 for all). Expression of EMT and fibrosis markers (acta2, col1a1, fn1, notch1, tgfb1 and zeb2) were comparable between Di- and Ex-treated mice, whereas macrophage infiltration and mediators of inflammation (ccl2, ccl4, ccl5, il1b, il6 and tnfa) were higher in Ex-treated mice. GO and KEGG pathway analyses revealed significant differences in cytokine-cytokine receptor interaction, leukocyte proliferation and mTOR pathway between the two groups. Peritoneal membrane thickening was reduced in EDA FN KO mice irrespective of Di- or Ex- treatment, and was associated with decreased inflammatory gene expression, EMT and fibrosis, approaching the levels in saline-treated WT mice.

Conclusion

Our data suggest that increased peritoneal EDA-FN expression contributes to peritoneal inflammation and fibrosis through induction of macrophage recruitment, and inflammatory and fibrotic processes. Both dextrose-based and icodextrin-based PD fluid increased EDA FN, while inflammatory processes were more pronounced with the latter. Also, Di and Ex may promote peritoneal membrane injury through distinct mechanisms.

Funding

• Government Support – Non-U.S.