Peritoneal dialysis fluid alters myeloid cell function and metabolism 3713

Abstract Description Peritoneal dialysis (PD) offers chronic kidney disease (CKD) patients a flexible alternative to haemodialysis. However, complications such as peritonitis and fibrosis limits long-term viability. Immune cells are key contributors to this. With immune cell function dependent on metabolism, the altered metabolic environment induced by PD fluids may impact their function. Two common forms of PD fluids include high glucose-based Physioneal and Icodextrin-based Extraneal, which may differentially affect metabolic pathways such as glycolysis. The impact of PD fluids on human immune cell metabolism and function was assessed. Short-term exposure to Physioneal significantly impaired myeloid cell metabolism (measured by extracellular flux analysis). We saw a reduction in functional receptors on myeloid cells (monocytes and neutrophils) and impaired short-term functional outputs, including phagocytosis and reactive oxygen species production. Conversely, Extraneal substantially enhanced glycolysis in both cell types which maintained short-term immune functions, but displayed reduced IL-6 and IL-10 production after LPS-stimulation (18-hours) compared to Physioneal and media controls. Evidently, PD fluids influence immune cell health and function, with varying impacts on metabolism and myeloid cell activation. Optimizing PD fluid composition, e.g. via metabolite additives, to preserve immune cell health is essential for improving the longevity of PD as a treatment option for CKD. Funding Sources Funded by MR/Y013816/1 Topic Categories Immune Mechanisms of Human Disease (HUM)