הידראָגען קענען באַשיצן ניר.
① Hydrogen and prevention and treatment of chronic kidney disease
As we know, the cells that make up the kidney have more mitochondria than those of other organs, because they need more energy to filter blood, so they consume more oxygen in the process of generating energy. More oxygen consumption means that kidney cells are at greater risk of oxidative stress. In addition, the kidney is an important organ, which is related to the release of metabolic wastes, toxins and pathogens in the blood. Therefore, NLRP3 inflammatory bodies in the kidney are very easy to be activated, which is due to the continuous exposure of pathogens in the blood stream recognized by macrophages and neutrophils.
In recent years, it has been reported that the activation of inflammatory bodies of NLRP3 is directly involved in the release of pro-inflammatory cytokines IL-1β and IL-18 in the kidney and the scorching of immune cells in the kidney (inflammatory cell death). In addition, NLRP3 regulates the apoptosis of renal tubular epithelial cells by interacting with mitochondria. In mitochondria, NLRP3 mediates the production of reactive oxygen species through oxidative stress and induces mitochondrial phagocytosis.
At present, the standard of treating CKD is to delay the progress of the disease by targeting multiple pathogenic pathways, but there is no good treatment to cure the disease. Therefore, it is very important to find a therapeutic target that can prevent chronic inflammation and thus avoid renal dysfunction.
Hydrogen shows a good prospect as CKD protective agent. The permeability and diffusivity of diatomic molecules allow hydrogen to make blood flow in the body, so that it can be filtered into the kidney and penetrate the mitochondria of kidney cells. By selectively scavenging OH produced by kidney mitochondria, hydrogen can prevent kidney mitochondria from autophagy, thus regulating the activation of NLRP3 inflammatory bodies and controlling the release of pro-inflammatory cytokines through reactive oxygen species. Hydrogen is a new tool to prevent renal dysfunction and chronic kidney diseases because of its role in chronic inflammation of NLRP3.
From January 2018 to December 2019, the hospitalized patients in Navy General Hospital were diagnosed as CKD3-4. A comparative study of 100 patients was conducted to evaluate the effect of hydrogen inhalation on renal function and quality of life of CKD patients.
Patients were randomly divided into an experimental group and a control group. Patients in the experimental group inhaled hydrogen plus basic treatment according to the plan, and the inhalation flow rate was 300ml/min for 6h/ day for 7 days. Patients in the control group were only given corresponding basic treatment.
The final result showed that compared with the control group, the renal function indexes (Scr, eGFR, BUN, CysC) and the scores of quality of life scale (PSQI, VAS) in the experimental group were improved in different degrees after hydrogen inhalation treatment. Analysis of the final results verified the role of hydrogen in protecting renal function and improving quality of life of CKD patients.
At present, the common treatment of chronic kidney disease is dialysis. As a new bioactive molecule, the role of hydrogen in hemodialysis and peritoneal dialysis has been reported one after another. Studies have found that hydrogen is of great value in alleviating the complications of dialysis.
A team of NaKayama from Tohoku University in Japan conducted standard hemodialysis for 21 dialysis patients for one month (three times a week). After using hydrogen-rich dialysate Rianu for six months, the results showed that the systolic blood pressure of the patients decreased significantly after dialysis, and the levels of plasma inflammatory factors monocyte chemoattractant protein and myeloperoxidase decreased significantly, indicating that adding hydrogen into the hemodialysis solution can improve the inflammatory response and control blood pressure.
In 2017, after 140 patients and 122 patients were treated with hydrogen-rich (30-80ppb) and standard hemodialysis respectively for 12 months, the team conducted comprehensive clinical effect analysis. The results showed that hydrogen-rich dialysis could alleviate the side effects such as fatigue, itching and hypertension after dialysis, and improve the quality of life of long-term dialysis patients.
In 2013, another Terawaki research team from Fukushima Medical University in Japan used hydrogen-rich dialysate to measure the redox state of albumin, a marker of oxidative stress, in order to clarify the influence of hydrogen molecules on peritoneum. The results showed that hydrogen-rich dialysate could increase reduced albumin, reduce oxidized albumin and relieve oxidative stress, which brought new hope to clinical peritoneal sclerosis treatment.
In recent years, Professor Guo Zhiyong, director of the Department of Nephrology, Changhai Hospital affiliated to Shanghai Naval Medical University, has been conducting research on hydrogen intervention in patients with nephropathy，Hydrogen inhalation intervention for patients with renal failure in 2018; And some ongoing clinical trials. See the following expert report for details!
② Hydrogen interferes with kidney calculi.
The prevalence of kidney calculi is high among adults in China, with almost one in 17 people suffering from. Calcium oxalate is the most common component of kidney calculi, which can interact with renal tubular epithelial cells, induce oxidative stress, inflammation and fibrosis, and further promote renal tubular cell injury.
The paper of Urology Department of the Third People's Hospital affiliated to Shanghai Jiaotong University School of Medicine on "Study on the Protective Effect of Hydrogen-rich Water on Renal Tubular Epithelial Injury in Rats Induced by Hyperoxaluria" shows that hyperoxaluria can increase the apoptosis of renal tubular epithelial cells, and hydrogen-rich water has a significant protective effect on this. For non-professional readers, this is a bit difficult to understand. In fact, this study hopes to tell readers that hydrogen can interfere with kidney calculi in animals.
The research results published by Professor Guo Zhiyong of Department of Nephrology, Changhai Hospital affiliated to Naval Medical University in 2021 showed that hydrogen-rich water (hydrogen concentration ≥2.5ppm) may improve oxidative stress, inflammation and fibrosis by inhibiting PI3K/AKT, NF-κB and TGF-β signal pathways, thus alleviating oxalic acid-induced kidney injury. It provides a new insight into the potential mechanism of hydrogen-rich water against oxalic acid-induced kidney injury.
Professor Guo Zhiyong's team published a clinical study in chinese journal of integrated traditional and western nephrology, September 2022, Vol.23, No.9, to observe the clinical effect of drinking hydrogen-rich water on blood lipid, urinary calcium level and renal function of kidney calculi patients. A total of 60 patients with kidney calculi from January 2021 to December 2021 were enrolled in this study. They were randomly divided into experimental group and control group, with 30 patients in each group. Patients in the experimental group drank 2L of hydrogen-rich water (NB-B81 multifunctional hydrogen molecular generator of Shanghai Nano-Technology Co., Ltd.) every day, while patients in the control group drank 2L of purified water every day for 3 months. It has been found that drinking hydrogen-rich water can reduce the levels of TC, TG, LDL-C and urinary calcium in patients with kidney calculi, and help to improve the renal function of patients.
③ Hydrogen reduces nephrotoxicity of drugs.
At present, the research focuses on the influence of hydrogen on chemotherapy drugs and antibiotics, and it is found that hydrogen can reduce the toxic and side effects of some drugs.
Cisplatin is a commonly used chemotherapy drug with therapeutic effect on sarcoma, malignant epithelial tumor, lymphoma and germ cell tumor. It has many side effects, among which the main adverse reaction is acute kidney injury, and this adverse reaction limits 25%~30% of patients to use it for treatment. Nakashima et al. reported that hydrogen can reduce the oxidative damage of kidney induced by cisplatin, reduce cell apoptosis, and reduce the levels of serum creatinine and urea nitrogen in experimental animals without affecting the effect of chemotherapy. Subsequently, Murase et al. confirmed the protective effect of hydrogen-rich solution on cisplatin-induced nephrotoxicity by CT and MRI.
Gentamicin is an aminoglycoside antibiotic, which can bind to bacterial ribosome 30s subunit and block the synthesis of bacterial protein. However, it should be monitored for renal insufficiency or long-term drug users. Murase et al. found that hydrogen can reduce gentamicin-induced nephrotoxicity by reducing oxidative damage in animal renal cortex.
④ Hydrogen reduces renal ischemia/reperfusion (I/R) injury.
Wang Fei et al. found that injection of hydrogen saturated saline can reverse the changes of MDA, MPO, BUN and serum creatinine after renal ischemia-reperfusion and reduce the level of inflammatory factors. At the same time, it can improve the activity of antioxidant enzymes and reduce the number of renal cell apoptosis. These results indicate that hydrogen saline can effectively interfere with renal ischemia-reperfusion injury.
Chihiro et al. established a rat renal I/R model by occluding the left renal artery and resecting the right kidney. After intraperitoneal injection of hydrogen-rich solution, it was found that the hydrogen-rich solution significantly reduced interstitial congestion, edema, inflammation and bleeding of renal tissue and inhibited the changes of mitochondrial morphology. At the same time, it was found that 8- hydroxydeoxyguanosine (8-OHdG) in serum decreased.