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2018 · Nakayama — Novel Haemodialysis Treatment Employing Molecular Hydrogen-Enriched Dialysis Solution Improves Prognosis of Chronic Dialysis Patients: A Prospective Observational Study

Original title: Novel haemodialysis (HD) treatment employing molecular hydrogen (H2)-enriched dialysis solution improves prognosis of chronic dialysis patients: A prospective observational study.

Super-Abstract

Over a mean observation period of 3.28 years, chronic haemodialysis patients treated with H₂-enriched dialysis solution had a 41% lower risk of combined all-cause mortality and major cardiovascular events compared to conventional haemodialysis (hazard ratio 0.59, 95% CI 0.38–0.92). This is one of the largest and longest H₂ outcome studies in a high-risk patient population. (Scientific Reports, 2018.)

Classified as a Pilot / Observational study using Unspecified. See Methodology for how we grade evidence.

Commentary

Chronic kidney disease patients on haemodialysis carry an exceptionally high burden of cardiovascular morbidity and mortality. Oxidative stress and inflammation — both of which H₂ is known to modulate — are particularly pronounced during dialysis due to the contact of blood with the dialysis membrane. Nakayama's group developed a novel haemodialysis system (E-HD) that delivers H₂-enriched dialysis solution (30–80 ppb) by in-line water electrolysis, thereby delivering H₂ directly into the bloodstream during each session — a fundamentally different route from drinking or inhalation. The prospective observational study enrolled 309 prevalent chronic HD patients allocated to E-HD (n=161) or conventional HD (n=148). The primary composite endpoint was all-cause mortality and non-lethal cardio-cerebrovascular events over a mean 3.28 years. E-HD patients had 41 events vs. 50 in the C-HD group. Multivariate Cox regression identified E-HD as an independent protective factor (HR 0.59, P significant) after adjustment for age, cardiovascular history, albumin, and CRP. Additionally, E-HD patients showed amelioration of post-dialysis hypertension with reduced need for antihypertensive medications.

Key quotes

  1. „Multivariate analysis of the Cox proportional hazards model revealed E-HD as an independent significant factor for the primary endpoint (hazard ratio 0.59; [95% confidence interval: 0.38-0.92]) after adjusting for confounding factors.“ — the key survival analysis: 41% risk reduction, independent of major confounders
  2. „post-dialysis hypertension was ameliorated with significant reductions in antihypertensive agents in the E-HD patients.“ — secondary benefit: blood pressure improvement — clinically relevant and objective
  3. „HD applying an H2-dissolved HD solution could improve the prognosis of chronic HD patients.“ — the authors' clinical conclusion after 3+ years of follow-up

Our assessment

This is one of the most impressive H₂ clinical studies in terms of outcome relevance — a 41% hazard reduction in all-cause mortality plus cardiovascular events over 3+ years in a high-risk population is clinically meaningful if valid. Published in Scientific Reports (Nature group). Limitations: this is a non-randomized, non-blinded observational study — allocation to E-HD vs. C-HD was not random, and residual confounding cannot be excluded despite the multivariate adjustment; both groups received identical dialysis protocols except for H₂, but baseline differences between groups are not fully described; 30–80 ppb H₂ is a relatively low concentration compared to drinking water studies; the study is from a single research group in Japan. These limitations mean this study, while compelling, cannot be considered proof of causal efficacy — a randomized controlled trial is urgently needed to confirm this result.

Study design

Abstract

Recent studies have revealed unique biological characteristics of molecular hydrogen (H2) as an anti-inflammatory agent. We developed a novel haemodialysis (E-HD) system delivering an H2 (30-80 ppb)-enriched dialysis solution by water electrolysis, and conducted a non-randomized, non-blinded, prospective observational study exploring its clinical impact. Prevalent chronic HD patients were allocated to either the E-HD (n = 161) group or the conventional HD (C-HD: n = 148) group, and received the respective HD treatments during the study. The primary endpoint was a composite of all-cause mortality and development of non-lethal cardio-cerebrovascular events (cardiac disease, apoplexy, and leg amputation due to peripheral artery disease). During the 3.28-year mean observation period, there were no differences in dialysis parameters between the two groups; however, post-dialysis hypertension was ameliorated with significant reductions in antihypertensive agents in the E-HD patients. There were 91 events (50 in the C-HD group and 41 in the E-HD group). Multivariate analysis of the Cox proportional hazards model revealed E-HD as an independent significant factor for the primary endpoint (hazard ratio 0.59; [95% confidence interval: 0.38-0.92]) after adjusting for confounding factors (age, cardiovascular disease history, serum albumin, and C-reactive protein). HD applying an H2-dissolved HD solution could improve the prognosis of chronic HD patients.

Source & links

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Screenshot — PubMed 29321509

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