Roos van Westrhenen

Cyclosporin A Induces Peritoneal Fibrosis and Angiogenesis during Chronic Peritoneal Exposure to a Glucose-Based, Lactate-Buffered Dialysis Solution in the Rat

Background/Aims: Cyclosporin A (CsA) stimulates the development of fibrosis. We investigated whether CsA contributes to peritoneal alterations induced by long-term exposure to dialysis solutions. Methods: Ten rats received peritoneal infusion of dialysis solution and oral CsA for 8 weeks. Eight received only the dialysis solution (controls). Peritoneal function was assessed at 8 weeks followed by sacrifice. The number of vessels was counted, fibrosis was assessed and hydroxyproline was determined. PCR was performed for vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β). Results: Histology revealed more fibrosis, hydroxyproline and vessels (thick walled) in CsA-exposed animals. Peritoneal transport was not different. The mRNA content of TGF-β, CTGF and VEGF was higher in CsA. Conclusion: CsA combined with exposure to dialysis solutions was associated with increased peritoneal fibrosis and angiogenesis.

Effects of reducing the lactate and glucose content of PD solutions on the peritoneum. Is the future GLAD

Background. Long-term peritoneal dialysis (PD) may lead to functional and morphologic changes in the peritoneal membrane, probably because of the continuous exposure to conventional dialysis solutions. Methods. The morphologic changes include neoangiogenesis and fibrosis. The authors of this article developed a long-term peritoneal exposure model in rats, in which the morphological alterations could be induced after daily peritoneal infusion of a 3.86% glucose/lactate-buffered conventional PD solution. Results and Conclusions. In the present article, a review of the model and of the results obtained with various available and experimental solutions is given. It appeared that high lactate concentrations contributed to the glucose-induced neoangiogenesis by pseudohypoxia. Glucose degradation products were probably more important in the induction of peritoneal fibrosis. The promising results of a combination of amino acids, glycerol and glucose, each in a low concentration, buffered with either pyruvate or bicarbonate/lactate, are presented and discussed. The combination of glycerol, amino acids and dextrose, dissolved in a bicarbonate/lactate buffer (GLAD), may be an option for a new generation of dialysis fluids.