Intermittent hypoxia in rat enhancing peritoneal membrane thickening through HIF-1α-induced cytokines in peritoneum

Background: Due to the high prevalence of both obstructive sleep apnea syndrome (OSA) and end-stage renal disease (ESRD), the co-existence of both conditions in peritoneal dialysis is demonstrated. Because OSA-induced chronic intermittent hypoxia is well-known, the hypoxia might worsen peritoneal membrane. Objective: We tested the influence of chronic intermittent hypoxia upon peritoneal membrane in a Sprague-Dawley rat model. Methods: Normal saline or 3.86% glucose peritoneal dialysis fluid (PDF) were intra-peritoneally administered twice a day as negative (NSS group) and positive controls (PDF group), respectively. Intermittent hypoxia was induced by using a hypoxic chamber with 10% O-2 for 8 hours a day plus twice-daily NSS injection (IH group). Results: At 12 weeks of the experiments, high serum TNF-alpha and IL-6 (but not IL-10) with normal renal and liver functions were demonstrated in the IH group (but not the PDF group). In parallel, local cytokines (TNF-alpha, IL-6, and IL-10 in peritoneal membrane) and peritoneal membrane thickness were increased whereas peritoneal membrane hypoxia (hypoxyprobe (TM) and hypoxia-inducible factor-1 alpha; HIF-1 alpha) was induced in both PDF and IH groups (more prominent in the PDF group). However, the increased vascular density in submesothelial area was established only in the PDF group. Conclusion: Intermittent hypoxia model induced local peritoneal membrane inflammation and enhanced peritoneal membrane thickness, at least in part, through a mechanism of hypoxia-induced HIF-1 alpha. Although peritoneal membrane alterations from PDF were more prominent than intermittent hypoxia, the combination between intermittent hypoxia with PDF utilization might facilitate peritoneal membrane failure, which will need more study.