Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

Abstract

BackgroundPeritoneal 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 (H2) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H2 on the peritoneal membrane of experimental PD rats.MethodEight-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 H2PD group (PD solution with dissolved H2 at 400 ppb). Furthermore, the influence of iron (FeCl3: 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H2PD groups). The H2PD solution was manufactured by bathing a PD bag in H2-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.ResultsIn 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 H2PD 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-H2PD group.ConclusionH2-dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.

Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

“…39,40 The hydrogen-containing peritoneal dialysate was first applied in rat model, and peritoneal fibrosis is effectively prevented after the administration of peritoneal dialysis. 20 There was a case report in which hydrogen-containing peritoneal dialysate and hemodialysis solution were applied for 63 days in an encapsulated peritoneal sclerosis (EPS) patient, and the peritoneal biopsy result showed that the intestinal cysts were not obvious. 21 The development of hydrogen-containing peritoneal dialysate is undoubtedly promising because of its safety and the antioxidant properties.…”

“…Hydrogen has already been reported to protect kidney, liver, heart, and lung from fibrosis . Studies have also suggested that peritoneal dialysate containing hydrogen could preserve MCs, indicating hydrogen may suppress peritoneal fibrosis . A clinical case report has indicated that hydrogen‐dissolved peritoneal dialysate could successfully treat a patient with encapsulating peritoneal sclerosis .…”

“…[16][17][18][19] Studies have also suggested that peritoneal dialysate containing hydrogen could preserve MCs, indicating hydrogen may suppress peritoneal fibrosis. 20 A clinical case report has indicated that hydrogen-dissolved peritoneal dialysate could successfully treat a patient with encapsulating peritoneal sclerosis. 21 However, the protective mechanism of hydrogen on MCs remains unexamined and needs to be further researched.…”

Genetic or pharmacologic blockade of enhancer of zeste homolog 2 inhibits the progression of peritoneal fibrosis

“…It has become a major alternative treatment for patients with end-stage renal disease worldwide [1]. However, persistent exposure of peritoneum to bio-incompatible peritoneal dialysis fluid (PDF) leads to peritoneal fibrosis, which decreases ultrafiltration capacity of peritoneum and limits its clinic application [2,3]. To date, there is no available treatment to prevent peritoneal fibrosis or halt its progression.…”

Encapsulating Peritoneal Sclerosis: Pathophysiology and Current Treatment Options

“…H 2 exerts anti-oxidative and anti-inflammatory effects [152]. In a less aggressive model of peritoneal damage than chlorhexidine administration, i.e., single injection of a neutral pH PD solution with low GDP content over 10 days in rats, the addition of H 2 mitigated submesothelial cell infiltration, mesothelial cell proliferation and apoptosis, and vimentin positivity, with the latter suggesting less MMT, but this could not be reconfirmed by other MMT markers [153]. Following an unsuccessful attempt to treat full-blown, histologically proven EPS with prednisolone for 30 days, Terawaki et al added dissolved H 2 to the hemodialysate, and 10 days later, also to the peritoneal lavage fluid.…”