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Perit Dial Int 28(5): 487-496
2008
© 2008 International Society for Peritoneal Dialysis
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Basic

A PYRUVATE-BUFFERED DIALYSIS FLUID INDUCES LESS PERITONEAL ANGIOGENESIS AND FIBROSIS THAN A CONVENTIONAL SOLUTION

Roos van Westrhenen1, Machteld M. Zweers1, Cindy Kunne1, Dirk R. de Waart2, Allard C. van der Wal3 and Raymond T. Krediet1

Division of Nephrology,1 Department of Medicine; Department of Experimental Hepatology 2 and Department of Cardiovascular Pathology,3 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Correspondence to: R.T. Krediet, Division of Nephrology, F4-215, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. c.n.deboer{at}amc.uva.nl

{diamondsuit} Background: Conventional lactate-buffered peritoneal dialysis (PD) fluids containing glucose and glucose degradation products are believed to contribute to the development of fibrosis and angiogenesis in the dialyzed peritoneum. To reduce potential negative effects of lactate, pyruvate was substituted as a buffer and its effects on peritoneal pathological alterations were studied in a chronic peritoneal exposure model in the rat.

{diamondsuit} Methods: 20 Wistar rats were infused intraperitoneally with pyruvate-buffered (n = 9) or lactate-buffered PD fluid. After 20 weeks of daily infusion, peritoneal function was assessed. In omental peritoneal tissue, the number of blood vessels was analyzed following alpha-smooth muscle actin staining. The degree of fibrosis was quantitated in Picro Sirius Red-stained sections and by assessment of the hydroxyproline content. Plasma lactate/pyruvate and betahydroxybutyrate/acetoacetate (BBA/AA) ratios were determined. Plasma and dialysate vascular endothelial growth factor (VEGF) levels were quantitated by ELISA.

{diamondsuit} Results: The mass transfer area coefficient of creatinine was higher and the dialysate-to-plasma ratio of sodium was lower in pyruvate-treated animals compared to the lactate-treated group (0.11 vs 0.05 mL/min, p < 0.05, and 78% vs 89%, p < 0.05). The BBA/AA ratio tended to be lower in the pyruvate animals (p = 0.07). The number of blood vessels was lower in pyruvate-treated animals (16 vs 37 per field, p < 0.001). Total surface area, luminal area, and wall/total area of the vessels were larger in the pyruvate group. The degree of fibrosis was lower in intersegmental and perivascular areas of pyruvate-exposed animals. Effluent VEGF was higher in the pyruvate group.

{diamondsuit} Conclusions: Replacement of lactate by pyruvate resulted in changes in peritoneal solute transport, accompanied by a reduction in both peritoneal membrane angiogenesis and fibrosis, suggesting potentially novel mechanisms to reduce glucose-driven alterations to the peritoneal membrane in PD patients.

KEY WORDS: Pyruvate; angiogenesis; pseudohypoxia; polyol pathway; peritoneal fibrosis.

Received 17 August 2007; accepted 24 March 2008.






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