Ongoing exposure to peritoneal dialysis fluid alters resident peritoneal macrophage phenotype and activation propensity

Abstract

Peritoneal dialysis (PD) is a more continuous alternative to haemodialysis, for patients with chronic kidney disease, with considerable initial benefits for survival, patient independence and healthcare cost. However, longterm PD is associated with significant pathology, negating the positive effects over haemodialysis. Importantly, peritonitis and activation of macrophages is closely associated with disease progression and treatment failure. However, recent advances in macrophage biology suggest opposite functions for macrophages of different cellular origins. While monocyte-derived macrophages promote disease progression in some models of fibrosis, tissue resident macrophages have rather been associated with protective roles. Thus, we aimed to identify the relative contribution of tissue resident macrophages to PD induced inflammation in mice. Unexpectedly, we found an incremental loss of homeostatic characteristics, anti-inflammatory and efferocytic functionality in peritoneal resident macrophages, accompanied by enhanced inflammatory responses to external stimuli. Thus, alterations in tissue resident macrophages may render longterm PD patients sensitive to developing peritonitis and consequently fibrosis/sclerosis.

Secondary Immunodeficiency Related to Kidney Disease (SIDKD)—Definition, Unmet Need, and Mechanisms

“…88,89 However, uncontrolled complement activation also contributes to hyperinflammation, cell injury, immunothrombosis, and multiorgan failure during COVID-19 infection. 90 In addition, monocytes/ macrophages from patients with ESKD have increased expression and activity of the macrophage scavenger receptors SR-A and CD36, [91][92][93] but decreased inducible nitric-oxide synthase expression 94 and phagocytic capability, e.g., of peritoneal macrophages in chronic PD and PD-induced peritonitis 95,96 and potentially also in alveolar macrophages in the context of pulmonary infections. ESKD reduces the cell number and cytotoxicity of natural killer (NK) cells in association with downregulation and modulation of ligand expression for activating receptors on NK cells.…”

Survival Analysis and Associated Factors of Technique Failure in Peritoneal Dialysis-Related Peritonitis: A Single-Center Study

“…A possible explanation for this is that the unit of PD duration in our study was years, not months. Tara et al 15 suggested that alterations in tissueresident macrophages may render long-term PD patients sensitive to developing peritonitis, which consequently puts them at a higher risk of Encapsulating Peritoneal Sclerosis(EPS), an urgent indication to discontinue PD. Because of improved worldwide survival rates, the number of patients with long PD duration is increasing.…”

“…Technique failure-related peritonitis may be associated with higher overall mortality for those on dialysis for ≥ 3 years when compared to those on it for < 3 years. This may be attributed to the in uence of long-term PD duration on peritoneum function 15 , which highlights the need for enhanced surveillance of long-term PD peritonitis patients, especially those with a PD duration longer than 3 years. To the best of our knowledge, this is the rst study to investigate the effect of PDRP history on technique failure and post-dialysis survival rates.…”

Ongoing Exposure to Peritoneal Dialysis Fluid Alters Resident Peritoneal Macrophage Phenotype and Activation Propensity

“…We’d also like to thank Sister Trish Smith from the Royal Manchester Children’s Hospital for the provision of Physioneal 40, Dr John Grainger (University of Manchester, UK) for the provision of the Cx3cr1 CreER :R26-eyfp mice as well as Prof. Judith E. Allen (University of Manchester, UK) for use of her Home Office animal licence and critical appraisal of the work. This manuscript was deposited as a pre-print version on BioRxiv prior to peer review ( 90 ).…”