Chronic kidney disease (CKD), which is globally on the rise, has become an urgent challenge from the perspective of public health, given its risk factors such as end-stage renal failure, cardiovascular diseases, and infections. The pathophysiology of CKD, including dialysis patients, is deeply associated with enhanced oxidative stress in both the kidneys and the entire body. Therefore, the introduction of a safe and widely applicable antioxidant therapy is expected as a measure against CKD. Electrolyzed hydrogen water (EHW) generated through the electrolysis of water has been confirmed to possess chemical antioxidant capabilities. In Japan, devices producing this water have become popular for household drinking water. In CKD model experiments conducted to date, drinking EHW has been shown to suppress the progression of kidney damage related to hypertension. Furthermore, clinical studies have reported that systemic oxidative stress in patients undergoing dialysis treatment using EHW is suppressed, leading to a reduction in the incidence of cardiovascular complications.
CKD Model | H | 2 | Load | Intervention | Observation | Main Findings | Oxidative Stress Marker |
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Dahl salt-sensitive rat (4 weeks old) [21] |
Ad libitum drinking in respective groups (n = 30 each) EHW (H2: 0.49 mg/L) DW (H2: 0.003 mg/L) FW (H2: <0.001 mg/L) |
N/A (fed by low sodium diet) |
48 weeks | No striking differences in BP among 3 groups. Lower in EHW than DW and FW in cardiac remodeling, glomerular sclerosis with tubulointerstitial fibrosis in the kidney, and increased cardiomyocyte diameter with interstitial fibrosis in the heart. |
Kidney: fewer nitrotyrosine, malondialdehyde, and ED1 cells in EHW than FW. Heart: less malondialdehyde in EW than FW, significantly higher Nrf2, and lower NADPH oxidase expression in EHW than FW. |
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Spontaneous hypertensive rat (8 weeks old) [66][84] |
Ad libitum drinking in respective groups (n = 72 each) HW (H2: 0.8–1.3 mg/L) vehicle |
N/A | 12 weeks | No striking differences in BP between two groups. Lower glomerular sclerosis score and higher renal blood flow and glomerular filtration rate in HW than vehicle. |
Lowered reactive oxygen species formation; upregulated the activities of superoxide dismutase, glutathione peroxidase, glutathione-S-epoxide transferase, and catalase, and suppressed NADPH oxidase in HW. Depressed pro-inflammatory cytokine expression in HW. Protective effect on mitochondrial function in HW. |
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Dahl salt-sensitive rat (7 weeks old) [67][85] |
Ad libitum drinking in respective groups (n = 18 in EW, 17 in FW) EHW (H2: 0.35 mg/L) FW (H2: 0.0 mg/L) |
Unilateral kidney I/R (fed a low sodium diet) |
6 weeks of preconditioning followed by intervention and 1 week post observation | Contralateral kidney and heart: less glomerular adhesion, cardiac fibrosis in EHW. |
Lower mRNA expression of NADPH oxidase 4 in heart in HW. Smaller number of ED-1 positive cells and nitrotyrosine in kidney and heart in EHW. |
Year (Ref.) | Study Design | H | 2 | Level of HD Solution | Number of Patients | Duration | Outcome |
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2009 [82][100] | Single-arm | ~99.0 ppb | 8 | 1 month | Significant decrease of methylguanidine | ||
2010 [83][101] | Single-arm | 49 ppb (average) | 21 | 6 months | BP reduction before and after HD Decrease of plasma MCP-1 and MPO (3rd tertile group) |
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2016 [84][102] | Parallel-arm | 47–196 ppb | 12 in EHD 38 in CHD |
7 months | Significant elevation in serum reduced albumin fraction pre- and post-HD in EW-HD No differences between EHD (post) and healthy subjects |
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2017 [85][103] | Parallel-arm | 30–80 ppb | 140 in EHD 122 in CHD |
12 months | Reduction of anti-hypertensive agents and subjective symptoms such as fatigue and pruritus | ||
2018 [86][104] | Parallel-arm | 30–80 ppb | 161 in EHD 148 in CHD |
3.28 years (average) | Reduction of post-HD BP in EHD Hazard ratio of EHD 0.59 for composite of all-cause mortality and non-lethal cardio-cerebrovascular events after adjusting for confounding factors |
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2021 [30] | Single-arm | 41–81 ppb | 63 | 2 months | Elevations of plasma MPO and thioredoxin at post-HD, elevation of plasma malondialdehyde at pre-HD and decrease at post-HD Decrease of VAS of fatigue |
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2021 [87][105] | Single-arm | 120–163 ppb | 95 | 2 months | Decrease of VAS of fatigue | ||
2022 [88][106] | Single-arm | Basal 47 ppb (average) to 154 ppb (average) ppb |
105 | 2 months | Decrease of plasma MPO pre-HD Decrease of NRS of fatigue |