When claudin-14 is idled, the kidney's filtering system works like it's supposed to. Essential minerals in the blood like calcium and magnesium pass through the kidneys and are reabsorbed back into the blood, where they are transported to cells to carry out basic functions of life.
But when people eat a diet high in calcium or salt and don't drink enough water, the small RNA molecules release their hold on claudin 14. An increase in the gene's activity prevents calcium from re-entering the blood, the study shows.
Hou and his team have found that claudin-14 blocks calcium from entering passageways called tight junctions in cells that line the kidney and separate blood from urine.
Without a way back to the bloodstream, excess calcium goes into the urine. Too much calcium in the urine can lead to stones in the kidneys or bladder. Intense pain develops when a large stone gets stuck in the bladder, ureter or urethra and blocks the flow of urine.
Hou's research supports the theory that people with a common variation in claudin-14 lose the ability to regulate the gene's activity, increasing the risk of kidney stones.
He is optimistic, however, that drugs could be developed to target the short stretches of RNA that are intimately linked to claudin 14. Drugs that mimic these so-called microRNAs could keep the activity of claudin-14 in check and reduce the likelihood that stones would form.
Also, it may one day be possible to develop a diagnostic test to measure levels of the claudin-14 protein excreted in urine. Elevated levels would indicate an increased risk of stones, and people could take steps to prevent stones by modifying their diet.
"Many genes likely play a role in the formation of kidney stones," Hou says. "But this study gives us a better idea of the way one
|Contact: Caroline Arbanas|
Washington University School of Medicine