Peritoneal dialysis fluid bioincompatibility and new vessel formation promote leukocyte-endothelium interactions in a chronic rat model for peritoneal dialysis.

Peritoneal dialysis (PD)-induced peritonitis leads to dysfunction of the peritoneal membrane. During peritonitis, neutrophils are recruited to the inflammation site by rolling along the endothelium, adhesion, and transmigration through vessel walls. In a rat PD-model, long-term effects of PD-fluids (PDF) on leukocyte-endothelium interactions and neutrophil migration were studied under baseline and inflammatory conditions. Rats received daily conventional-lactate-buffered PDF (Dianeal), bicarbonate/lactate-buffered PDF (Physioneal) or bicarbonate/lactate buffer (Buffer) during five weeks. Untreated rats served as control. Baseline leukocyte rolling and N-formylmethionyl-leucyl-phenylalanine (fMLP) induced levels of transmigration in the mesentery were evaluated and quantified by intra-vital videomicroscopy and immunohistochemistry. Baseline leukocyte rolling was unaffected by buffer treatment, approximately 2-fold increased after Physioneal and 4-7-fold after Dianeal treatment. After starting fMLP superfusion, transmigrated leukocytes appeared outside the venules firstly after Dianeal treatment (15 minutes), thereafter in Physioneal and Buffer groups (20-22 minutes), and finally in control rats (>25 minutes). Newly formed vessels and total number of transmigrated neutrophils were highest in Dianeal-treated animals, followed by Physioneal and Buffer, and lowest in control rats and correlated for all groups to baseline leukocyte rolling (r = 0.78, P < 0.003). This study indicates that the start of inflammatory neutrophil transmigration is related to PDF bio(in)compatibility, whereas over time neutrophil transmigration is determined by the degree of neo-angiogenesis.

Factors contributing to peritoneal tissue remodeling in peritoneal dialysis.

Peritoneal dialysis (PD) is associated with functional and structural changes of the peritoneal membrane. In this review we describe factors contributing to peritoneal tissue remodeling, including uremia, peritonitis, volume loading, the presence of a catheter, and the PD fluid itself. These factors initiate recruitment and activation of peritoneal cells such as macrophages and mast cells, as well as activation of peritoneal cells, including mesothelial cells, fibroblasts, and endothelial cells. We provide an overview of cytokines, growth factors, and other mediators involved in PD-associated changes. Activation of downstream pathways of cellular modulators can induce peritoneal tissue remodeling, leading to ultrafiltration loss. Identification of molecular pathways, cells, and cytokines involved in the development of angiogenesis, fibrosis, and membrane failure may lead to innovative therapeutic strategies that can protect the peritoneal membrane from the consequences of long-term PD.