Dissolved molecular hydrogen (H(2)) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

BACKGROUND: Peritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H(2)) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H(2) on the peritoneal membrane of experimental PD rats. METHOD: Eight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8–11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H(2)PD group (PD solution with dissolved H(2) at 400 ppb). Furthermore, the influence of iron (FeCl(3): 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H(2)PD groups). The H(2)PD solution was manufactured by bathing a PD bag in H(2)-oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis. RESULTS: In the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H(2)PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H(2)PD group. CONCLUSION: H(2)-dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H(2) in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.