Low-Concentration Hydrogen Inhalation and Chronic Kidney Disease/Dialysis Complications - Based on Previous Research Findings -

MiZ Corporation (Kamakura City, Kanagawa Prefecture), in collaboration with research groups from the University of California, Berkeley, Keio University, and Osaka Metropolitan University Graduate School of Medicine, has reported findings from joint research on chronic kidney disease (CKD), diabetic kidney disease (DKD), and dialysis complications involving oxidative stress through multiple peer-reviewed papers, academic presentations, and observational cases. This press release organizes the potential role of low-concentration hydrogen inhalation in preserving kidney function by suppressing oxidative stress in vascular endothelium, and re-proposes safe hydrogen inhalation practices, which are essential prerequisites for delivering these findings to society.

Summary of this Release

- The kidneys are vulnerable organs to oxidative stress and ischemia-reperfusion injury due to high ATP consumption in tubules and abundant mitochondria.

- Hydrogen has been reported to selectively scavenge hydroxyl radicals (•OH) and suppress oxidative stress in vascular endothelium, potentially contributing to the inhibition of CKD/DKD progression and mitigation of dialysis complications.

- Low-concentration hydrogen inhalation, maintaining device output concentration at or below the demonstrated environmental value of 10% by volume, poses no explosion risk and serves as a prerequisite for applied research, including in dialysis settings.

Background: Kidneys, Oxidative Stress, and Related Academic Achievements

The kidneys not only filter blood to excrete waste products as urine but also reabsorb essential water and electrolytes in the tubules to maintain the body's internal environment. This reabsorption requires a significant amount of energy, hence the abundance of mitochondria in tubular cells. On the other hand, although the kidneys require a large amount of oxygen, their oxygen supply has little margin. Consequently, they are susceptible to damage from "ischemia-reperfusion," where blood flow temporarily decreases and then returns. Furthermore, in cases of hypertension and diabetes, increased oxidative stress makes the vascular endothelium prone to inflammation. This is deeply involved in the onset and progression of chronic kidney disease (CKD). In hemodialysis, contact of blood with the dialyzer membrane elevates inflammatory responses, placing additional burden on the vascular endothelium throughout the body.

MiZ Corporation's main academic achievements related to the kidneys are as follows:

In 2020, the company obtained a patent based on clinical cases concerning diabetic nephropathy, hypertensive kidney disease, and side effects associated with dialysis, related to low-concentration hydrogen inhalation.

In 2021, in a co-authored paper with the University of California, Berkeley, and Keio University, they reported the potential role of hydrogen in selectively scavenging hydroxyl radicals (•OH) and contributing to the inhibition of chronic kidney disease (CKD) progression.

In 2023, they published a review article on the potential role of molecular hydrogen in the research field of CKD and diabetic kidney disease (DKD). They also gave an oral presentation at the 34th Annual Meeting of the Japanese Society for Apheresis, titled "Potential for Mitigation of Hemodialysis Complications by Hydrogen Inhalation."

In 2025, through joint research with Osaka Metropolitan University Graduate School of Medicine, they reported that hydrogen administration protected the vascular endothelial glycocalyx in bleeding model rats and improved survival rates.

Furthermore, in 2026, in a co-authored paper with Keio University and others, they academically verified the risk of in-vivo hydrogen explosion in high-concentration hydrogen inhalers. The paper recommends a transition to low-concentration hydrogen inhalation, which carries no explosion risk, from a safety perspective (Ichikawa et al., 2026).

Meanwhile, in 2015, MiZ Corporation announced, based on a review of existing literature and empirical studies assuming an inhalation environment, that there is a risk of explosion when hydrogen concentration exceeds 10% by volume in a normal environment. The value of 10% by volume is a demonstrated value assuming an inhalation environment, distinct from the theoretically defined lower explosive limit of hydrogen under ideal conditions (Ichikawa et al., 2026).

Definitions of Terms

Chronic Kidney Disease (CKD)

A condition where kidney function is reduced (GFR < 60 mL/min/1.73m²) or kidney damage such as proteinuria persists for 3 months or longer. Hypertension, diabetes, and oxidative stress are major risk factors.

Diabetic Kidney Disease (DKD)

Chronic kidney disease caused by diabetes. It impairs tubular and glomerular function through microvascular damage and oxidative stress.

Vascular Endothelial Glycocalyx

A mucosal layer covering the vascular endothelium. It plays roles in vascular permeability, anti-inflammation, and antithrombotic functions. Its breakdown due to bleeding or oxidative stress exacerbates CKD and organ damage.

Hydroxyl Radical (•OH)

The most potent reactive oxygen species. There are no endogenous enzymes to scavenge it. It is a common causative agent in oxidative stress-related diseases, including CKD and DKD.

Hydr ogen Inhaler

Hydr ogen Inhaler: A device that generates hydrogen gas (H₂) through water electrolysis and delivers it into the body via a respiratory interface. The selection of device output concentration is a design variable determining safety. MiZ Corporation advocates for designs that maintain device output concentration at or below the demonstrated environmental value of 10% by volume (Ichikawa et al., 2026).

Demonstrated Environmental Value (10% by Volume)

Demonstrated Environmental Value (10% by Volume): The demonstrated threshold for explosion risk in a hydrogen inhalation environment (exceeding 10% by volume). This value was announced by MiZ Corporation in 2015 based on a review of existing literature and empirical studies assuming an inhalation environment, taking into account inhalation-specific conditions such as device outlet, exhalation pathway, human body, and device design (Ichikawa et al., 2026).

Classical Lower Flammable Limit (LFL) 4% by Volume

Reported by Coward & Jones (1952) in U.S. Bureau of Mines Bulletin 503. This is the theoretical minimum concentration measured under conditions of 1 atm and room temperature in a closed vertical tube, where a pre-mixed hydrogen and air ignited statically allows upward flame propagation to be continuous. It primarily targets closed system scenarios such as containers, piping, and mines.

Relationship between LFL 4% and Demonstrated Value 10%

A hydrogen inhalation environment is an open system where hydrogen gas generated by water electrolysis at atmospheric pressure is continuously released into the atmosphere, continuously diffuses and dilutes with indoor air, and is supplied as a flowing gas to the inhalation pathway. This fundamentally differs in three aspects – spatial conditions, mixing state, and flow state – from the measurement conditions of the classical LFL, which assumes pre-mixed static gas within containers and piping. Both are distinct indicators measuring different physical conditions, making the demonstrated value of 10% by volume a reasonable basis for evaluating the safety of hydrogen inhalation devices.

Key Findings and Cases

Hydrogen's Protective Effect on Vascular Endothelium and Kidney Function

Hydrogen is thought to protect the body from oxidative stress by reacting with highly oxidizing hydroxyl radicals (•OH) and converting them into water molecules (Figure 1).

Figure 1: The kidneys are organs susceptible to oxidative stress due to the high energy and oxygen consumption required for filtration and reabsorption in blood purification.

Hydrogen, when taken into the body through inhalation or drinking hydrogen-rich water, spreads throughout the body via diffusion and blood flow. Therefore, the vascular endothelial protective effect of hydrogen may extend to the vascular endothelium of the kidneys, and it is expected to contribute to inhibiting the progression of renal failure and suppressing endothelial inflammation associated with dialysis.

In fact, numerous academic papers have been published on the relationship between hydrogen intake and kidney function (Figure 2). Some of these include studies where effects on the body were observed with the inhalation of low-concentration hydrogen gas, as low as 1% by volume.

Furthermore, our company is involved with patients undergoing hemodialysis.