Kidney Stone Mystery Solved

Photo: CT of kidney

Presence of kidney stones:
Researchers provide evidence
to explain why some people are
more prone to the condition
than others; © Washington
University

"Now, we finally have a more complete picture detailing why some people develop kidney stones and others do not," says Doctor Jianghui Hou. "With this information, we can begin to think about better treatments and ways to determine a person's risk of the condition, which typically increases with age."

Because kidneys function the same way in mice as in humans, the new findings can help scientists understand the root causes of kidney stones in patients. The mouse model used in the study can also serve as a platform for the preclinical testing of novel treatments for the condition, the researchers say.

Most kidney stones form when the urine becomes too concentrated, allowing minerals like calcium to crystallise and stick together. Diet plays a role in the condition — not drinking enough water or eating too much salt, which binds to calcium, also increases the risk of stones.

A fact is: Genes are partly to blame. A common genetic variation in a gene called claudin-14 recently has been linked to a substantial increase in risk — roughly 65 per cent — of getting kidney stones. In the new study, the researchers have shown how alterations in the gene's activity influence the development of stones.

Typically, the claudin-14 gene is not active in the kidney. The new research shows that its expression is dampened by two snippets of RNA, a sister molecule of DNA that essentially silence the gene. When claudin-14 is idled, the kidney's filtering system works like it is 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 do not 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.

MEDICA.de; Source: Washington University in St. Louis