Is Hydrogen Water Good For Your Kidneys?

If you are wondering "Is hydrogen water good for your kidneys?", this article delves into the mechanisms of hydrogen in the treatment of kidney diseases and explores its potential clinical applications. 

Hydrogen Administration and Mechanisms

Before we delve into "Is hydrogen water good for your kidneys?", let's learn a little about hydrogen. Hydrogen can be administered in several forms: inhalation, oral, intravenous, or local application. Its small molecular size allows it to rapidly diffuse into suborganelles like mitochondria and the nucleus.

Once inside the cells, hydrogen selectively scavenges harmful reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and peroxynitrite (ONOO−), while sparing beneficial ROS like superoxide (O2−) and hydrogen peroxide (H2O2). Despite the confirmed regulatory effects of hydrogen on signal transduction pathways, the specific mechanisms remain largely unknown.

Therapeutic Potential and Clinical Trials

The therapeutic applications of hydrogen were first reported in 1975, when significant tumor size reduction was observed in mice exposed to a hydrogen-oxygen mixture. In 2007, Ohsawa et al. highlighted hydrogen's antioxidant and antiapoptotic properties, demonstrating its ability to protect the brain from ischemia-reperfusion injuries. Since then, hydrogen's potential in treating kidney diseases such as acute kidney injury (AKI), renal fibrosis, polycystic kidney disease, and renal cell carcinoma has been extensively studied in cellular and animal models.

Despite these promising results, clinical trials are still limited. More large-scale, randomized controlled trials are needed to fully understand hydrogen's efficacy, optimal dosage, timing, and form of administration in treating kidney diseases.

Biological Effects of Hydrogen

Anti-Oxidation

Hydrogen reduces oxidative stress by neutralizing harmful free radicals. It activates the Nrf2/ARE pathway, increasing the transcription of antioxidant enzyme genes like heme oxygenase 1 (HO-1).

It also boosts the expression of endogenous antioxidants such as superoxide dismutase, catalase, and reduced glutathione (GSH), which collectively help mitigate oxidative damage. 

Immune System Regulation

Basic and clinical studies have shown that hydrogen has significant anti-inflammatory effects. It reduces the expression of pro-inflammatory cytokines like interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α).

In conditions like diabetic nephropathy (DN) and acute kidney injuries, hydrogen's ability to modulate immune responses and reduce inflammation is particularly beneficial.

Regulation of ER Stress

Endoplasmic (ER) stress occurs when pathological stress leads to an accumulation of unfolded proteins. Hydrogen has been shown to reduce ER stress-related protein levels and alleviate tissue damage in models of myocardial ischemia-repreticulum erfusion injury.

Although research on hydrogen's role in regulating ER stress in kidney diseases is still scarce, it represents a promising future research direction.

Mitochondria Quality Control

Hydrogen helps maintain mitochondrial function by regulating ROS production. This is crucial in conditions like urate nephropathy, where excessive ROS can lead to mitochondrial depolarization and further damage.

Currently, there are no reports on the regulation of mitochondrial function by hydrogen in kidney disease treatment, but it remains a potential area for future studies.

Effects of Hydrogen (H2) on Cell Death: A Concise Overview

Anti-apoptosis

Hydrogen (H2) plays an antiapoptotic role by regulating factors involved in programmed cell death. It inhibits proapoptotic factors like Bax and caspases while enhancing antiapoptotic factors such as Bcl-2 and Bcl-xl. Studies show that H2 can reduce muscle injury and increase skin flap survival by modulating apoptotic proteins, though its exact mechanisms in kidney disease are not fully understood.

Autophagy

Autophagy helps maintain cell homeostasis and renal function. H2 regulates this process, preventing excessive autophagy that can cause tissue damage. Research indicates H2 alleviates kidney injury from chronic intermittent hypoxia by reducing ER stress and activating autophagy, though further studies are needed.

Pyroptosis

Pyroptosis, involving reactive lipid oxygen accumulation and cell death, plays a role in kidney diseases like AKI and renal fibrosis. H2 may regulate pyroptosis pathways to treat these conditions, but more research is required to confirm this hypothesis.

Ferroptosis

Ferroptosis, distinct from other cell death forms, involves iron-dependent ROS accumulation and lipid peroxidation. H2 reduces levels of the ferroptosis regulator HMGB1 and increases HO-1 activity, a cytoprotective enzyme, suggesting its potential in treating kidney diseases. While the mechanisms are not fully clear, H2 offers promising directions for future research.

The Role of Kidney Diseases and Hydrogen Therapy

 

Drug-Induced Nephrotoxicity

Drug-induced nephrotoxicity, especially from drugs like cisplatin, a chemotherapy agent, affects 20-30% of patients despite precautions like hydration. Cisplatin accumulates in the kidneys, depleting antioxidants and increasing reactive oxygen species (ROS), leading to kidney damage. Studies show that hydrogen gas and hydrogen water can protect against cisplatin-induced nephrotoxicity by reducing ROS and restoring kidney function.

Renal Fibrosis

Renal fibrosis, a common progression in chronic kidney disease, affects many older adults and a significant portion of the global population. Research indicates hydrogen water can alleviate renal fibrosis by preventing harmful cell transformations and maintaining kidney health. Hydrogen-rich saline (HRS) also shows promise in reducing renal fibrosis through mechanisms like autophagy activation.

Ischemia-Reperfusion Injury (IRI)

IRI, common in organ transplants, causes significant kidney damage due to ROS generation. Hydrogen therapy, including hydrogen gas and HRS, has been shown to protect against IRI by reducing oxidative stress and inflammation, improving kidney function, and enhancing survival rates in animal models.

Renal Calculi

Kidney stones, often composed of calcium oxalate, cause significant discomfort and renal damage. Hydrogen gas has been found to reduce crystal deposition and protect against oxidative damage in kidney tissues, indicating a potential therapeutic role in preventing and managing kidney stones.

Hemodialysis

Hemodialysis patients experience increased oxidative stress, contributing to cardiovascular diseases. Studies suggest that hydrogen-enriched dialysate can reduce oxidative stress, potentially lowering cardiovascular risks and improving patient outcomes.

Chronic Allograft Nephropathy (CAN)

CAN is a major cause of long-term kidney transplant failure. Research shows that hydrogen water can reduce the severity of CAN, suggesting it as a potential therapeutic approach to improve graft survival by decreasing oxidative stress and inflammation.

Sepsis-Related Acute Kidney Injury (AKI)

Sepsis-related AKI has high mortality rates. Hydrogen-rich solutions have shown protective effects against septic AKI by reducing inflammation and oxidative stress, improving kidney function, and increasing survival in animal models.

Other Functions

Hydrogen water has shown protective effects against renal injury in hypertensive rats by reducing ROS and inflammation, improving mitochondrial function, and preserving renal health. It also mitigates kidney damage in various conditions, such as CIH-induced injury and acute renal injury from severe pancreatitis or contrast agents.

In summary, hydrogen therapy, through hydrogen gas or hydrogen-rich water/solutions, shows promising protective effects against various kidney diseases by reducing oxidative stress and inflammation, suggesting its potential as a therapeutic strategy for kidney health.

Conclusion

Currently, there are few reports of hydrogen causing adverse cellular reactions. Studies on its mutagenicity, genotoxicity, and toxicity show no significant harmful effects. Saitoh found no toxicity in rats drinking hydrogen-enriched water. Nakao observed minor changes in liver enzymes within normal ranges in a pilot study. No studies indicate hydrogen negatively impacts renal disease treatment.

Hydrogen has demonstrated anti-oxidative, anti-inflammatory, and anti-apoptotic properties, showing therapeutic potential in kidney diseases like renal calculi, fibrosis, and drug-induced nephrotoxicity. However, the exact mechanisms remain unclear. Future research should investigate hydrogen's specific mechanisms and potential negative effects in kidney disease, with large-scale clinical trials needed to confirm its efficacy and cost-efficiency.

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