A major breakthrough! A new method for treating kidney stones for the first time in 30 years
August 16, 2016 Source: Bio Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)]; In a new study, the researchers found evidence that a natural fruit extract dissolves calcium oxalate crystals, the most common component of human kidney stones. This discovery may lead to the first progress in the treatment of calcium oxalate stones in 30 years. The relevant research results were published online in the Nature Journal on August 8, 2016, and the title of the paper is "Molecular modifiers reveal a mechanism of pathological crystal growth inhibition". The author of the paper is Jeffrey Rimer, associate professor of chemical engineering at the University of Houston, and John Asplin, a nephrologist at Litholink.
This study provides the first evidence that the compound hydroxycitrate (HCA) is a substance that effectively inhibits the growth of calcium oxalate crystals and, under certain conditions, actually dissolves these crystals. The researchers also explained how it works.
According to Rimer, these findings are the result of a combination of experimental, computational, and human studies.
Kidney stones are small, hard mineral deposits that form in the kidneys, affecting up to 12% of men and 7% of women. Hypertension, diabetes and obesity can increase this risk, and the reported incidence is also rising.
In the past three decades, there has not been much change in the prevention and treatment of kidney stones. Doctors tell patients who are at risk of getting stones to drink plenty of water and avoid eating oxalate-rich foods such as rhubarb, okra, spinach and almonds. They often recommend taking citrate (CA) in the form of potassium citrate, a supplement that delays the growth of calcium oxalate crystals, but some people cannot tolerate the side effects it produces.
Asplin pointed out that HCA is a possible treatment option. HCA is chemically similar to CA and can also be used as a dietary supplement.
"HCA is expected to be a potential treatment to prevent kidney stones. HCA may be better than CA (in the form of potassium citrate) in treatment," the researchers wrote.
At the same time, studies on CA and HCA found that although these two compounds inhibit the growth of calcium oxalate crystals, HCA is more potent and exhibits unique properties that facilitate the development of new therapies.
The researchers then used atomic force microscopy (AFM) to study the interaction between calcium oxalate crystals and CA and HCA under real growth conditions. According to Rimer, this technique allows them to record crystal growth in near-molecular resolution in real time.
The first author of the paper, Jihae Chung, a graduate student at the University of Houston who worked on the Rimer lab, noticed that when the calcium oxalate crystals were exposed to a specific concentration of HCA, these AFM micrographs recorded that the crystal was indeed shrinking. Rimer suspects that this initial finding is abnormal because it is very rare to observe that the crystal is dissolved in highly supersaturated solutions. The most effective inhibitors reported in the literature are simply to prevent this crystal growth.
The results show that Chung's initial findings are correct. Once the researchers confirmed that it was possible to dissolve calcium oxalate crystals in a supersaturated solution, they studied why this situation occurred.
Giannis Mpourmpakis from the University of Pittsburgh and his graduate student Michael G. Taylor used density functional theory (DFT), a highly accurate calculation method, to study the structure and properties of materials. Solve how HCA and CA bind to calcium and calcium oxalate crystals. They found that HCA binds more strongly to the surface of the calcium oxalate crystals, creating a tension that appears to be relieved by the release of calcium and oxalate ions, causing the crystals to dissolve.
HCA is also tested in human subjects. Seven people took the supplement within three days, which allowed the researchers to determine that HCA was excreted through the urine, which is necessary for this supplement to function as a therapy.
Rimer said that although the study laid the groundwork for designing an effective drug, the problem still exists. He said long-term safety, dose and further human clinical trials are still needed.
"But our initial findings are very promising," he said. "If it works in the body, like the clinical trials we do in the lab, then HCA has the potential to reduce the incidence of patients with chronic kidney stones.
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