Abstract
BackgroundGlucose is a primary osmotic agent in peritoneal dialysis (PD) solutions, but its long-term use causes structural alteration of the peritoneal membrane (PM). Hyperbranched polyglycerol (HPG) is a promising alternative to glucose. This study was designed to compare the cellular responses of human peritoneal mesothelial cells (HPMCs) to these two different osmotic agents in a hypertonic solution using transcriptome analysis.MethodsCultured HPMCs were repeatedly exposed to HPG-based or Physioneal 40 (PYS, glucose 2.27%) hypertonic solutions. Transcriptome datasets were produced using Agilent SurePrint G3 Human GE 8 × 60 microarray. Cellular signaling pathways were examined by Ingenuity Pathway Analysis (IPA). Protein expression was examined by flow cytometry analysis and Western blotting.ResultsThe HPG-containing solution was better tolerated compared with PYS, with less cell death and disruption of cell transcriptome. The levels of cell death in HPG- or PYS- exposed cells were positively correlated with the number of affected transcripts (HPG: 128 at day 3, 0 at day 7; PYS: 1799 at day 3, 212 at day 7). In addition to more affected “biosynthesis” and “cellular stress and death” pathways by PYS, both HPG and PYS commonly affected “sulfate biosynthesis”, “unfolded protein response”, “apoptosis signaling” and “NRF2-mediated oxidative stress response” pathways at day 3. PYS significantly up-regulated HLA-DMB and MMP12 in a time-dependent manner, and stimulated T cell adhesion to HPMCs.ConclusionThe lower cytotoxicity of hypertonic HPG solution is in agreement with its transient and minimal impact on the pathways for the “biosynthesis of cell constituents” and the “cellular stress and death”. The significant up-regulation of HLA-DMB and MMP12 by PYS may be part of its initiation of immune response in the PM.
Highlights
Glucose is a primary osmotic agent in peritoneal dialysis (PD) solutions, but its long-term use causes structural alteration of the peritoneal membrane (PM)
Cell growth recovery of Human peritoneal mesothelial cell (HPMC) was improved in treatment with Hyperbranched polyglycerol (HPG) but not with PYS The impact of the hypertonic HPG solution compared to PYS control on HPMC survival was first determined by measuring lactate dehydrogenase (LDH) release
All these data suggested that following multiple exposures to HPG compared to PYS, there was less HPMC death in HPG groups compared to PYS group
Summary
Glucose is a primary osmotic agent in peritoneal dialysis (PD) solutions, but its long-term use causes structural alteration of the peritoneal membrane (PM). Numerous studies have demonstrated that inclusion of glucose in the conventional PD solutions largely contributes to peritoneal membrane (PM) damage and UF failure [4,5,6,7,8], and its high level or long-term peritoneal load is positively correlated with an increase in all-cause and cardiovascular disease mortality, low residual renal function (RRF) and dialysate to plasma ratio of creatinine in PD patients [9, 10]. It has been proposed that a non-glucose based biocompatible osmotic agent in a PD solution may preserve long-term integrity of PM structure and function, resulting in a delay in PD technique failure
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
