(Press-News.org) Anyone who has suffered from kidney stones is keenly aware of the lack of drugs to treat the condition, which often causes excruciating pain.
A new mouse study, however, suggests that a class of drugs approved to treat leukemia and epilepsy also may be effective against kidney stones, researchers at Washington University School of Medicine in St. Louis report.
The drugs are histone deacetylase inhibitors, or HDAC inhibitors for short. The researchers found that two of them — Vorinostat and trichostatin A — lower levels of calcium and magnesium in the urine. Both calcium and magnesium are key components of kidney stones.
The research is available online in the Journal of the American Society of Nephrology.
"We're hopeful this class of drugs can dissolve kidney stones because its effects on reducing calcium and magnesium are exclusive to kidney cells," said senior author Jianghui Hou, PhD, assistant professor of medicine. "In the mice, we achieved dramatic effects at a fraction of the dosage used to treat leukemia and without significant side effects."
Most kidney stones form when the urine becomes too concentrated, allowing calcium and magnesium to crystallize and stick together. Intense pain develops when stones get stuck in the urinary tract and block the flow of urine.
Diet can play a role in the condition. Not drinking enough water or eating a diet with too much salt, which promotes calcium to be released into the urine, increases the risk of stones. Some people also are genetically prone to developing kidney stones, and they naturally release too much calcium into the urine.
Typically, doctors recommend drinking lots of water to help pass kidney stones from the body. Thiazide, a type of drug used to treat high blood pressure, sometimes is prescribed to treat the stones because it reduces calcium in the urine. But the drug also increases magnesium in urine, countering its effectiveness against kidney stones.
In the new study, Hou and his colleagues showed that Vorinostat, approved to treat leukemia and epilepsy, and trichostatin A, an antifungal drug, mimic a natural process in the kidney that reabsorbs calcium and magnesium into the urine.
Kidneys, in addition to filtering waste from the blood into the urine, also play an essential role in reclaiming minerals that the body needs to carry out basic functions of life. Normally, some calcium and magnesium in the blood are filtered into the urine and then reabsorbed back into the blood, depending on the body's need for these essential minerals.
Hou's earlier work showed this process is heavily dependent on the activity of a gene called claudin-14. When the activity of claudin-14 is idled, the kidney's filtering system works like it's supposed to. But when the gene is activated, calcium and magnesium are blocked from re-entering the blood.
The gene's expression is controlled by two snippets of RNA, a sister molecule of DNA, Hou's previous research has shown.
As part of the new study, Hou and his colleagues found that Vorinostat and trichostatin A do not act directly on the claudin-14 but mimic these so-called micro-RNA molecules, keeping the activity of the gene in check. That the drugs can modify the activity of micro-RNAs make them attractive as potential treatments for kidney stones.
In the mice, small doses of Vorinostat, for example, reduced calcium levels in the urine by more than 50 percent and magnesium levels by more than 40 percent. Similar results were noted for trichostatin A.
"Kidney cells were very sensitive to the drug," Hou explained. "We used one-twentieth of the dose typically used in humans and achieved significant results. We now want to test the drug in clinical trials for patients with kidney stones."
Mice don't develop kidney stones, so it will be important to test the drugs against kidney stones in patients, but the current study provides proof of principle that HDAC inhibitors regulate the same pathway that leads to kidney stones, he said.
INFORMATION:
The research was supported by the National Institutes of Health (NIH), (R01-DK084059 and P30-DK079333) and the American Heart Association (0930050N).
Gong Y, Himmerkus N, Plain A, Bleich M and Hou J. Epigenetic regulation of microRNAs for controlling CLDN14 expression as a mechanism for renal calcium handling. Journal of the American Society of Nephrology. July 30, 2014.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Potential drug therapy for kidney stones identified in mouse study
2014-08-14
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
Broader organ sharing won't harm liver transplant recipients
2014-08-14
New research shows that broader sharing of deceased donor livers will not significantly increase cold ischemia time (CIT)—the time the liver is in a cooled state outside the donor suggesting that this is not a barrier to broader sharing of organs. However, findings published in Liver Transplantation, a journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, do indicate that broader sharing of organs will significantly increase the percentage of donor organs that are transported by flying rather than driving. ...
Scientists study 'talking' turtles in Brazilian Amazon
2014-08-14
AUDIO:
These are vocalizations made between adults and hatchlings (individual sounds repeated for the listener's benefit).
Click here for more information.
Turtles are well known for their longevity and protective shells, but it turns out these reptiles use sound to stick together and care for young, according to the Wildlife Conservation Society and other organizations.
Scientists working in the Brazilian Amazon have found that Giant South American river turtles actually ...
Scientists fold RNA origami from a single strand
2014-08-14
RNA origami is a new method for organizing molecules on the nanoscale. Using just a single strand of RNA, many complicated shapes can be fabricated by this technique. Unlike existing methods for folding DNA molecules, RNA origamis are produced by enzymes and they simultaneously fold into pre-designed shapes. These features may allow designer RNA structures to be grown within living cells and used to organize cellular enzymes into biochemical factories. The method, which was developed by researchers from Aarhus University (Denmark) and California Institute of Technology ...
New analysis links tree height to climate
2014-08-14
MADISON, Wis. — What limits the height of trees? Is it the fraction of their photosynthetic energy they devote to productive new leaves? Or is it their ability to hoist water hundreds of feet into the air, supplying the green, solar-powered sugar factories in those leaves?
Both factors — resource allocation and hydraulic limitation — might play a role, and a scientific debate has arisen as to which factor (or what combination) actually sets maximum tree height, and how their relative importance varies in different parts of the world.
In research to be published in ...
New gene editing method shows promising results for correcting muscular dystrophy
2014-08-14
DALLAS – August 14, 2014 – UT Southwestern Medical Center researchers successfully used a new gene editing method to correct the mutation that leads to Duchenne muscular dystrophy (DMD) in a mouse model of the condition.
Researchers used a technique called CRISPR/Cas9-mediated genome editing, which can precisely remove a mutation in DNA, allowing the body's DNA repair mechanisms to replace it with a normal copy of the gene. The benefit of this over other gene therapy techniques is that it can permanently correct the "defect" in a gene rather than just transiently adding ...
9/11 dust cloud may have caused widespread pregnancy issues
2014-08-14
Pregnant women living near the World Trade Center during 9/11 experienced higher-than-normal negative birth outcomes, according to a new working paper by Princeton University's Woodrow Wilson School of Public and International Affairs.
These mothers were more likely to give birth prematurely and deliver babies with low birth weights. Their babies - especially baby boys - were also more likely to be admitted to neonatal intensive care units after birth. The study, led by the Wilson School's Janet Currie and Hannes Schwandt, was released by the National Bureau of Labor ...
Reduced testosterone tied to endocrine-disrupting chemical exposure
2014-08-14
Washington, DC—Men, women and children exposed to high levels of phthalates - endocrine-disrupting chemicals found in plastics and some personal care products – tended to have reduced levels of testosterone in their blood compared to those with lower chemical exposure, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).
Testosterone is the main sex hormone in men. It contributes to a variety of functions in both sexes, including physical growth and strength, brain function, bone density and cardiovascular ...
Vitamin D Deficiency May Reduce Pregnancy Rate in Women Undergoing IVF
2014-08-14
Washington, DC—Women with a vitamin D deficiency were nearly half as likely to conceive through in vitro fertilization (IVF) as women who had sufficient levels of the vitamin, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).
Long known for its role in bone health, vitamin D is a steroid hormone that is emerging as a factor in fertility. Animal studies have shown that the hormone, which is produced in the skin as a result of sun exposure as well as absorbed from some fortified foods, affects fertility ...
Scripps Research Institute chemists uncover powerful new click chemistry reactivity
2014-08-14
LA JOLLA, CA—August 14, 2014—Chemists led by Nobel laureate K. Barry Sharpless at The Scripps Research Institute (TSRI) have used his click chemistry to uncover unprecedented, powerful reactivity for making new drugs, diagnostics, plastics, smart materials and many other products.
The new SuFEx—Sulfur Fluoride Exchange—reactions enable chemists to link molecules of their choice together using derivatives of a common commercial chemical considered essentially inert. The Sharpless team made this chemical reliably and predictably reactive. Astonishingly, acid-base constraints ...
Adults with autism at higher risk of sexual victimization: York University study
2014-08-14
Adults with autism are at a higher risk of sexual victimization than adults without, due to lack of sex education, but with improved interventions that focus on sexual knowledge and skill building, the risk could be reduced, according to a recent study by York University researchers.
"Adults with Autism Spectrum Disorder (ASD) gain more of their sexual knowledge from external sources such as the internet and the television whereas social sources would include parents, teachers and peers," says Professor Jonathan Weiss in the Faculty of Health and the CIHR Chair in Autism ...