Date Published: April 23, 2019
Publisher: Public Library of Science
Author(s): Masatora Yamasaki, Motoaki Miyazono, Maki Yoshihara, Atsuhiko Suenaga, Masato Mizuta, Makoto Fukuda, Shuichi Rikitake, Yuji Ikeda, Michael Bader.
Various factors are considered to be mechanisms of the increase in the sizes of cysts in patients with polycystic kidney disease. Vasopressin is one of the causes, and drinking large volumes of water shows an effect of suppressing an increase in cysts. On the other hand, it is known that hydrogen-rich water reduces oxidative stress and has a good effect on kidney injury. We examined whether drinking large volumes of hydrogen-rich water affected the increase in the sizes of cysts. Forty 5-week-old PCK rats were randomly assigned to four groups: C(Control), purified water; W(Water), water with sugar; H(Hydrogen), hydrogen-rich water; WH(Water+Hydrogen), hydrogen-rich water with sugar. They consumed water from 5 to 15 weeks of age. The intake of water in the groups in which sugar was added to the water (W, WH) significantly increased in comparison to C, but there was no significant change in the serum Creatinine concentration. The kidney weight per body weight in W was significantly decreased in comparison to C. The kidney weights in H and WH were significantly increased in comparison to W. There were no significant differences in the ratio of the cross-sectional area of the cysts to the whole area among the groups. This experiment showed that the effect of drinking large volumes of hydrogen-rich water was not significantly different from that of normal water, in terms of preventing an increase in the size of cysts in PCK rats. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.
Autosomal-dominant polycystic kidney disease (ADPKD) causes multiple cysts in the bilateral kidneys, which increases and impairs normal kidney tissue. Approximately half ADPKD patients progress to end-stage renal failure by 60 years of age. ADPKD is the most common hereditary kidney disease, and affects one 1 in 4,000 people in Japan, and is the cause of dialysis in 3.5% of dialysis patients . There have been no specific treatments until recent years. However, tolvaptan, a vasopressin V2-receptor antagonist, was reported to have inhibitory effects against the increase in kidney volume and the reduction in the kidney function .
ADPKD is caused by mutations of two genes (PKD1, PKD2) encoding Polycystin 1 (PC 1) and Polycystin 2 (PC 2). Thus far, there is no fundamental therapy for the disease. In patients with an increased kidney volume, the renal function gradually declines, progressing to renal failure, and renal replacement therapy is required. In polycystic kidney (PKD) cells, the functional abnormality reduces the concentration of intracellular Ca2+, the activity of phosphodiesterase (PDE) enzyme, which degrades cyclic AMP (cAMP), decreases and the intracellular cAMP concentration increases. As a result, the function of cAMP-dependent protein kinase A (PKA) is enhanced, various signal pathways (EGF/EGFR, Wnt, Raf/MEK/ERK, JAK/STAT, mTOR, and others) are activated, and cell proliferation occurs. On the other hand, the vasopressin (AVP) R2 receptor present in the renal tubule (collecting duct) is activated by AVP and works to increase water permeability through adnylcyclase (AC) and cAMP to retain moisture. In PKD cells, the increase in cAMP caused by vasopressin increases the sizes of cysts. Thus, drinking a large amount of water and tolvaptan (a vasopressin V 2 receptor) antagonist is expected to suppress the increase in cyst numbers and suppress the progression of renal disorder .
In our trial, there was no significant difference in the creatinine level or cyst size. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.