Abstract
BackgroundLong-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.Materials and methodsIn 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.ResultsDaily exposure of LS fluid during a period of 8 weeks resulted in a peritoneal increase of αSMA 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 TGFβ1, TNFα, INFγ, and MIP-1β 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.ConclusionDevelopment 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.
Highlights
Continuous and long-term treatment with peritoneal dialysis (PD) promotes an inflammatory response which eventually leads to a progressive remodeling of the peritoneal membrane [1]
Immunohistological analysis of peritoneal biopsies revealed that exposure to buffered solutions (BLS) significantly prevented (P = 0.01) the accumulation of α αSMA positive cells in the parietal membrane when compared to conventional LS PDF (C: 0.020 ± 0.016, S: 0.026 ± 0.026, LS: 0.075 ± 0.072, BLS: 0.016 ± 0.014), (Fig. 1b, c)
Analysis of the peritoneal effluents collected after 8 weeks of daily exposure to the different treatments performed by standard peritoneal equilibrium test (PET) revealed no differences between the groups regarding the volume of ultrafiltration
Summary
Continuous and long-term treatment with peritoneal dialysis (PD) promotes an inflammatory response which eventually leads to a progressive remodeling of the peritoneal membrane [1]. While experimental and clinical data suggest a better preservation of peritoneal morphologic and functional features upon bicarbonate/lactate solution compared to conventional PD solutions, the implication on the inflammatory cell population in this novel solution has been poorly defined To overcome this knowledge gap, our recently developed uremic mouse PD exposure model [14] was used in the present study to compare a pH neutral low-GDP bicarbonate/ lactate-buffered solution (BLS) with a standard high GDPs lactate (LS) PD fluid in respect of inflammation, fibrosis, and vascularisation. We demonstrate that the enhanced fibrotic and angiogenic response observed in LS-exposed mouse was prevented upon BLS exposure This preservation of the peritoneal integrity by BLS was accompanied with a lower number of CD4+ IL-17+ cells, higher levels of macrophage-related pro-inflammatory cytokines and with a higher ratio of M1 macrophages over M2 subset. Peritoneal recruitment of M1 macrophages and lower number of C D4+ IL-17+ cells might explain the peritoneal integrity preservation observed in BLS-exposed mouse
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