Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Potential drug therapy for kidney stones identified in mouse study

15.08.2014

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.


Wikimedia Commons, E.K. Kempf

Pictured is the surface of a kidney stone with calcium oxalate crystals.

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. 

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.

Caroline Arbanas | Eurek Alert!
Further information:
https://news.wustl.edu/news/Pages/27237.aspx

Further reports about: HDAC inhibitors Medicine activity blood drugs leukemia therapy urinary tract urine

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>