Peritoneal effluent-derived mononuclear phagocyte immune profiles may relate to cardiac function in peritoneal dialysis
Micky Karsten, Nico Hahn, Puck Vree, Luke C. Davies, Marc G. Vervloet, Jan Van Den Bossche, Lily JakuljIntroduction
Cardiovascular-kidney-metabolic (CKM) syndrome is characterized by chronic inflammation that may drive heart failure. Peritoneal dialysis (PD), while lifesaving, may induce local and systemic inflammation through bioincompatible intraperitoneal solutions, potentially amplifying CKM syndrome. We investigated peritoneal mononuclear phagocyte phenotypes, key-drivers of inflammation, and whether these correlate with systemic inflammation and cardiac function in PD-treated patients.
Methods
We collected patient-matched peripheral blood-derived and PD-effluent (PDE)-derived cells from 13 adult PD-treated patients and characterized peritoneal immune populations by unbiased clustering using a mononuclear phagocyte-selective flow cytometry panel. In a subsequent cohort of 21 PD-treated patients, we correlated cardiac function [left ventricular global longitudinal strain (LV-GLS)] with peritoneal immune profiles and serum inflammatory markers.
Results
Mononuclear phagocytes predominated in PDE and exhibited a more differentiated phenotype than blood-derived mononuclear phagocytes. Unbiased clustering revealed substantial overlap between blood- and PDE-derived classical monocytes. A higher PDE-derived differentiated monocyte-to-dendritic cell ratio was related to more impaired LV-GLS. Peritoneal monocytes showed reduced antigen-presenting capacity in patients with impaired cardiac function, potentially influenced by diabetes mellitus. Systemic inflammatory markers were largely undetectable in this stable PD-cohort.
Conclusion
Our findings suggest a link between peritoneal immune characteristics and cardiac dysfunction, characterized by a shift towards a higher monocyte-to-dendritic cell ratio in PD-treated patients with more pronounced cardiac dysfunction. The directionality and mechanisms underlying this association remain to be established and given the limited patient number and cross-sectional design, these findings should be considered as hypothesis-generating. The applied flow cytometry and unsupervised clustering approach offers a promising and scalable tool for future in-depth investigation of the peritoneal immune microenvironment and its relation to PD-related clinical outcomes, including CKM sequelae.