Oxidative stress during peritoneal dialysis: implications in functional and structural changes in the membrane

Area of Science:

• Nephrology
• Biomedical Engineering
• Pathology

Background:

• Long-term peritoneal dialysis (PD) is associated with progressive peritoneal fibrosis, membrane hyperpermeability, and ultrafiltration failure.
• The precise mechanisms underlying these detrimental effects on the peritoneal membrane are not fully elucidated.

Purpose of the Study:

• To investigate the role of reactive oxygen species (ROS) generated by conventional PD solutions in causing functional and structural alterations of the peritoneal membrane in vivo.
• To evaluate the protective effects of an antioxidant (N-acetylcysteine) and an angiotensin II receptor blocker (losartan) against these PD-induced changes.

Main Methods:

• Sprague-Dawley rats were administered conventional PD solution (3.86% glucose) with or without N-acetylcysteine (NAC) or losartan intraperitoneally twice daily for 12 weeks.
• Control rats received sham injections.
• Functional parameters (drain volume, solute transport) and structural/molecular markers (membrane thickness, eNOS, TGF-β1, VEGF, collagen I, hsp47 expression, lipid peroxides) were assessed.

Main Results:

• PD solution administration led to significantly reduced drain volume and glucose transport, but increased creatinine transport, membrane thickness, and eNOS expression compared to controls.
• Increased omental expression of TGF-β1, VEGF, collagen I, and hsp47, along with elevated lipid peroxides and dialysate Ang II and VEGF, were observed in PD-treated rats.
• Both NAC and losartan treatments effectively prevented all the observed detrimental changes induced by the PD solution.

Conclusions:

• Reactive oxygen species generated by conventional PD solutions are a major contributor to peritoneal fibrosis and membrane hyperpermeability.
• Antioxidants and angiotensin II receptor blockers demonstrate potential as therapeutic strategies to preserve the structural and functional integrity of the peritoneal membrane during long-term PD.