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Why People Get Kidney Stones, New Discovery

Kidney stone

Here’s something you might not know: the kidneys in mice and humans function the same way. This has proved to be good news for the latter, because it has allowed scientists to uncover why some people are more likely to get kidney stones than others.

Kidney stones have a genetic component

A kidney stone is composed of substances in the urine that come together to form a solid stone-like object in the kidney. A stone may remain in the kidney or travel through the urinary tract, where it may get stuck along the way and cause intense pain.

Approximately 1 million Americans experience kidney stones each year, and now investigators at Washington University School of Medicine in St. Louis believe they know why some people are more susceptible to developing these stones, thanks to a mouse model.

Among the risk factors for the formation of kidney stones is diet; specifically, not drinking enough water or consuming too much salt, which attaches to calcium and increases the risk of stone formation. (See “About kidney stones” below)

Another risk factor is genetics. A gene called claudin-14 normally is not active in the kidney. However, previous research showed that a variation in the gene is associated with about a 65% increased risk of developing kidney stones.

Now investigators have uncovered the secrets of the claudin-14 gene and kidney stones. They discovered that the gene is usually inactive because its activity is prevented by two tiny pieces of RNA. This inactivity is healthy, because it allows calcium and magnesium in the blood to flow through the kidneys and be reabsorbed into the bloodstream.

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But here is where dietary factors kick in. People who consume too much calcium or salt and don’t drink enough water can cause the RNA molecules to loosen their grip on claudin-14, which in turn stops calcium from going back into the bloodstream.

Because claudin-14 blocks calcium, the mineral has no place to go except into the urine. An excessive amount of calcium in the urine can result in the formation of stones in the kidneys or bladder.

About kidney stones
Kidney stones can be as small as a grain of sand or as large as a golf ball or even bigger. In addition to the dietary risk factors mentioned, other factors include obesity, family history, being male (kidney stones occur more often in men), being white, and the presence of gout, high blood pressure, inflammatory bowel disease, kidney disease, and hyperparathyroidism.

Although there are four major types of kidney stones, the most common type consists primarily of calcium along with other waste products. In most people, the kidneys eliminate extra calcium in urine, but for others, calcium remains in the kidneys.

Struvite kidney stones develop after a urinary tract infection. These stones contain magnesium and ammonia. Uric acid stones form when the urine is too acidic, which can occur among people who eat a great deal of meat. Kidney stones composed of cystine (an amino acid in the diet) are rare.

According to the study’s senior author, Jianghui Hou, PhD, assistant professor of medicine, their discovery allows them to “begin to think about better treatments and ways to determine a person’s risk of the condition, which typically increases with age.” Knowing why people get kidney stones may even help researchers find “ways to prevent stones from developing in the first place,” noted Hou.

Gong Y et al. Claudin-14 regulates renal CA++ transport in response to CaSR signaling via a novel microRNA pathway. The EMBO Journal, 2012 Feb 28
National Institute of Diabetes and Digestive and Kidney Diseases

Image: Wikimedia Commons