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Human Genetics: Kidney Stones - Causes, Treatment and Cure

written by: •edited by: Paul Arnold•updated: 7/9/2009

Kidney stones are clumps of material created from substances found in urine. Small stones pass straight through the body without difficulty. Large stones may become stuck and block the passage of urine, causing great pain. Kidney stone prevention and treatment may be boosted by gene discoveries.

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    Causes of Kidney Stones

    The human body's two kidneys are filters - cleansing the blood of water and waste products to create urine. Sometimes the salt and minerals found in the urine aggregate to form crystalline clumps known as kidney stones. There are several different types of stones, but most contain calcium. They become problematic when they are so large that they move out of the kidney and block the ureter, the tubes that connect the kidney to the bladder.

    There are several factors which are known to influence the development of kidney stones - namely - low fluid intake, a diet high in proteins, some medications, and an abnormally shaped kidney or the presence of only one kidney.

    Another important factor is family history, which suggests a strong genetic influence. And so scientists have gone hunting for the genes that may increase an individual's risk of forming kidney stones. Knowing which genes are involved will be useful for several reasons;

    • A genetic test could be created to spot those at increased risk, and their diet could be modified accordingly to minimise the risk.
    • New kidney stones treatments could be developed that could prevent kidney stones from forming.
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    Kidney Stones and Genetic Causes

    • In 2003 scientists at the University of Texas discovered six genetic mutations in the same gene, and concluded that any one of these mutations can cause the body to absorb too much calcium, thereby increasing the risk of kidney stones.

    • In 2008 a team from the School of Veterinary Medicine at the University of California, Davis, discovered genetic mutations in the SLC2A9 gene in Dalmatians. The faults lead to elevated uric acid levels, and may provide insight into human kidneys stones, because high uric acid levels can cause the stones to form.

    • In June 2009 researchers at a private bio-pharmaceutical company (deCODE Genetics) discovered a common genetic variant that is associated with the formation of kidney stones. The scientists carried out a genome wide scan of 3, 773 cases and 42, 510 controls. The variant was found in the CLDN14 gene on chromosome 21.

    According to the research about 60% of the population carries two copies of a single-letter variation (SNP - single nucleotide polymorphism) on this gene, and that increases risk by about 65%, compared with those who do not possess the variant.

    The CLDN14 gene codes for a membrane protein that regulates the passage of ions and solutes between cells. The scientists believe that the gene variants may somehow lead to excess calcium being passed into the urine, which plays a major part in the formation of kidney stones.

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    Kidney Stone Prevention

    The next step in the deCODE work will be to figure out just how the single nucleotide polymorphism brings about this increased risk, and to find a molecular pathway that can be targeted by therapeutics.

    As many kidneys stones are created by a deficiency in the way the body handles calcium, research in this area may also be of benefit to studies into osteoporosis, where bone mineral density is reduced.

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    • Stefansson K et al. Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density. Nature Genetics Published online: 28 June 2009 | doi:10.1038/ng.404