Conditions

Expression Of Claudin-14 Cause Kidney Stone

A new study conducted at Washington University School of Medicine in St. Louis found the reason behind development of kidney stone. Their discovery opens the door to find effective drug treatments and a test that could assess a person’s risk of kidney stones.

“Now, we finally have a more complete picture detailing why some people develop kidney stones and others do not,” says senior author Jianghui Hou, PhD, assistant professor of medicine. “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.”

The research was conducted in mice. 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 noted. The study is detailed in the EMBO Journal.

Kidney stones or renal calculi occur when calcium in the urine crystallizes and aggravates. Less water and too much salt consumption could accelerate the formation of kidney stone. However common genetic variation in a gene called claudin-14 has been linked to a substantial increase in risk of getting kidney stones. Defects in claudin-14 function result in a broad range of renal diseases, including hypomagnesemia, hypercalciuria and nephrolithiasis. This is detailed in the community forum Organogenesis.

Normally the claudin-14 is found in the kidney in an inactive state. The genes expression of claudin-14 is hindered by two snippets of RNA, sister molecules of DNA. However when people eat more calcium or salt rich diet, then the hindrance formed by the two RNA molecules is removed. This results in accelerated activity of gene which prevents calcium from re-entering the blood.

Hou and team found that claudin-14 blocks calcium from entering ‘tight junctions,’ passageways in cells that line the kidney and separate blood from urine.

Excess calcium goes in to urine since there is no way to return to blood stream. 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.

However Hou believes that this findings will pave way for new avenues for treating kidney stones, drugs that could 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 chance of stone formation.

"Many genes likely play a role in the formation of kidney stones," Hou said.

"But this study gives us a better idea of the way one of the major players work. Now that we understand the physiology of the condition, we can start to think about better treatments or even ways to prevent stones from developing in the first place," he added.

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