Kidney Week

Abstract: SA-PO437

Peritoneal Fibrosis Activated by Glucose-Based Peritoneal Dialysis Solutions Can Be Reverted by XyloCore

Session Information

• Home Dialysis - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

• Masola, Valentina, Department of Biomedical Science, University of Padova, Padova, Italy

Valentina Masola, PhD

• D'Apolito, Luciano, Biogem, Institute of Molecular Biology and Genetics, Ariano Irpino, Italy

Luciano D'Apolito, PhD

• D'Alessandro, Angelo, Department of Biochemistry and Molecular Genetics, University of Colorado, Denver – Anschutz Medical Campus, Aurora, Colorado, United States

Angelo D'Alessandro, PhD

• Vecchi, Luigi, Unit of Nephrology, Santa Maria Hospital, Terni, Italy

Luigi Vecchi, MEd

• Bonomini, Mario, Department of Medicine, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy

Mario Bonomini, MD

• Capasso, Giovambattista, Biogem, Institute of Molecular Biology and Genetics, Ariano Irpino, Italy

Giovambattista Capasso, MD, PhD

• Trepiccione, Francesco, Biogem, Institute of Molecular Biology and Genetics, Ariano Irpino, Italy

Francesco Trepiccione, MD, PhD

• Onisto, Maurizio, Department of Biomedical Science, University of Padova, Padova, Italy

Maurizio Onisto

• Prosdocimi, Tommaso, Iperboreal Pharma Srl, Pescara, Italy

Tommaso Prosdocimi, PhD

• Divino-Filho, Jose C., Division of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden

Jose C. Divino-Filho, MD, PhD

• Arduini, Arduino, Iperboreal Pharma Srl, Pescara, Italy

Arduino Arduini, MD

Background

One of the major drawbacks of peritoneal dialysis (PD) is the decline in ultrafiltration capacity. Prolonged exposure to traditional high glucose-based PD fluids can induce severe pathological conditions such as peritoneal fibrosis, angiogenesis and epithelial-mesenchymal transition (EMT), ultimately leading to membrane failure. The introduction of new glucose-sparing PD solutions may provide a means to restore peritoneal filtration capacity.

Methods

Mesothelial cells were initially exposed to conventional PD solution for two days, followed by treatment with XyloCore (a novel glucose-sparing PD solution maintaining iso-osmolality by replacing glucose with L-carnitine and xylitol) for the subsequent three days, along with appropriate controls. Similarly, rats were subjected to peritoneal dialysis for 15 days with daily intraperitoneal injections of conventional glucose-based PD fluids, followed by XyloCore or appropriate controls for another 15 days. Multi-photon microscopy (MPM) was utilized to assess blood flow, grade of fibrosis, and vessel spreading. Gene and protein expression of TGF-b, VEGF, EMT, and inflammatory markers were investigated in both in vitro and in vivo samples.

Results

Both in vitro and in vivo findings demonstrated that XyloCore treatment mitigated the upregulation of TGF-b, VEGF, EMT, and inflammatory markers induced by conventional PD fluids. Moreover, XyloCore treatment in rats led to decreased collagen deposition in the sub-mesothelium and reduced compactness of collagen fibers. Additionally, the number of vessels and their branching were contracted.

Conclusion

XyloCore appears to have the ability to reverse the fibrotic process initiated by conventional PD fluids. This potential could facilitate functional recovery and potentially extend the functional life of the peritoneal membrane, even in individuals undergoing peritoneal dialysis with conventional solutions for prolonged periods of time.

Funding

• Private Foundation Support