Differences in peritoneal response after exposure to low-GDP bicarbonate/lactate-buffered dialysis solution compared to conventional dialysis solution in a uremic mouse model

作者：Cuenca, M. Vila; Keuning, E. D.; Talhout, W.; Paauw, N. J.; van Ittersum, F. J.; ter Wee, P. M.; Beelen, R. H. J.; Vervloet, M. G.^*; Ferrantelli, E.

来源：International Urology and Nephrology, 2018, 50(6): 1151-1161.

DOI：10.1007/s11255-018-1872-3

• Peritoneal dialysis
• Macrophage
• IL17
• Fibrosis
• Angiogenesis

Long-term exposure of conventional peritoneal dialysis (PD) fluid is associated with structural membrane alterations and technique failure. Previously, it has been shown that infiltrating IL-17-secreting CD4+T cells and pro-fibrotic M2 macrophages play a critical role in the PD-induced pathogenesis. Although more biocompatible PD solutions are recognized to better preserve the peritoneal membrane integrity, the impact of these fluids on the composition of the peritoneal cell infiltrate is unknown.
In a uremic PD mouse model, we compared the effects of daily instillation of standard lactate (LS) or bicarbonate/lactate-buffered solutions (BLS) and respective controls on peritoneal fibrosis, vascularisation, and inflammation.
Daily exposure of LS fluid during a period of 8 weeks resulted in a peritoneal increase of alpha SMA and collagen accompanied with new vessel formation compared to the BLS group. Effluent from LS-treated mouse showed a higher percentage of CD4(+) IL-17(+) cell population while BLS exposure resulted in an increased macrophage population. Significantly enhanced inflammatory cytokines such as TGF beta 1, TNF alpha, INF gamma, and MIP-1 beta were detected in the effluent of BLS-exposed mice when compared to other groups. Further, immunohistochemistry of macrophage subset infiltrates in the BLS group confirmed a higher ratio of pro-inflammatory M1 macrophages over the pro-fibrotic M2 subset compared to LS.
Development of the peritoneal fibrosis and angiogenesis was prevented in the BLS-exposed mice, which may underlie its improved biocompatibility. Peritoneal recruitment of M1 macrophages and lower number of CD4(+) IL-17(+) cells might explain the peritoneal integrity preservation observed in BLS-exposed mouse.

• 出版日期2018-6