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 patie
|Contact: Diane Duke Williams|
Washington University School of Medicine