Solved! The Mystery of the Stones

Kidney stones strike an estimated 1 million Americans each year.

Those who have experienced them say it is among the most excruciating pain known to man (or woman).

Now, new research provides evidence to explain why some people are more prone to develop the condition than others. The discovery by scientists at Washington University School of Medicine in St. Louis opens the door to finding 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 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.”

Although the research was in mice, the new findings will help scientists to understand the root causes of kidney stones in patients because their kidneys function the same way as ours.

Most kidney stones form when the urine becomes too concentrated, allowing minerals such as calcium to crystallize and stick together.  Diet plays a role – not drinking enough water or eating too much salt (which binds to calcium) increases the risk of stones.

But genes are also partly to blame. A common genetic variation called claudin-14 has recently been linked to a 65% increased risk of kidney stones.

In the new study, the researcher demonstrated how alterations in the gene’s activity influence the development of stones.  Typically, the claudin-14 gene is not active in the kidney. Its expression is dampened by two snippets of RNA, that essentially silence the gene.  When claudin-14 is idled, the kidney’s filtering system works like it’s supposed to. Essential minerals in the blood 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 and the subsequent increase in the gene’s activity prevents calcium from re-entering the blood.  Without a way back to the bloodstream, excess calcium passes into the urine. Too much calcium in the urine leads to the development of stones in the kidneys or bladder.

Then when a large stone gets stuck in the bladder, ureter or urethra the flow of urine is blocked and the characteristic intense pain, that can reduce even the most mild-mannered man to a cursing, foul-mouthed monster, develops.

People with the common, genetic variation in claudin-14 lose the ability to regulate the gene’s activity, increasing the risk of kidney stones.

The results of this research lead to the hope that drugs that will keep the activity of claudin-14 in check can be developed.  Additionally, it may 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 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.”

For the million or so sufferers and their loved ones we guess that day can’t come soon enough.

A vitamin-a-day may do more harm than good

One of the few businesses that has benefitted from the current U.S. recession has been the dietary supplements industry. While some predicted that falling disposable income would hamper sales of vitamins and supplements, the opposite actually occurred: As more people lost their jobs and ability to pay for healthcare, many turned to supplements to remain healthy and ward off expensive doctor visits and pharmaceutical drugs. 

However, the results of two studies, published last week may signal a  reverse of the fortunes of this $30 billion per year industry.

Last week researchers from the Cleveland Clinic announced that vitamin E can enhance chances of prostate cancer. A study involving more than 35,000 men found that those who took a daily dose of 400 IU of vitamin E had a 17% increased incidence of prostate cancer than men who took a placebo.

For the typical man, there appears to be no benefit in taking vitamin E and, in fact, there may be some harm,” said Dr. Eric Klein, an internationally renowned prostate cancer expert who served as the national study coordinator.

This surprising news was followed in short order by a report that dietary supplements can also increase mortality rate in older women.

The Iowa Women’s Health Study, which started in 1986, set out to determine to what degree diet and other lifestyle factors influence risk of chronic disease.

By the end of the study period in 2008, a total of 41,836 postmenopausal women were investigated – of which 15,594 had died. Multivitamins, vitamin B6, folic acid, iron, magnesium, zinc and copper were all associated with increased total mortality risk.  Supplemental iron was most strongly associated with increased mortality whereas, calcium supplements, were associated with a decreased risk.

Study leader Dr Lisa Harnack, associate professor of epidemiology at the University of Minnesota, said: “Among the elderly, use of supplements is widespread, often with the intention of attaining health benefits by preventing chronic diseases. Our study raises concerns regarding their long-term safety.”

SRxA’s Word on Health won’t be taking any chances. No more once-a-day for us!

The Great Vitamin D Debate

Over the past decade there has been a lot of conflicting advice about the benefits of vitamin D and calcium.

Like many of our readers, this confusion has left us pondering: How much milk should we be drinking?  Are supplements really necessary? Can we get all the vitamin D we need from the sun?

We were therefore very interested to read the results of The Institute of Medicine’s (IOM) recently released review on dietary reference intakes for the vitamin D and calcium. Their latest recommendations were based on a review of more than 1,000 studies and reports as well as testimony from scientists and stakeholders. Interestingly, the IOM looked at a range of health outcomes, far beyond bone health.  These included, but were not limited to, cancer, cardiovascular disease, hypertension, diabetes, metabolic syndrome, falls, immune response, neuropsychological functioning, physi­cal performance, preeclampsia, and reproductive outcomes.

Although they acknowledged that both are important for health, overall, the committee concluded that the majority of Americans are receiving adequate amounts of both calcium and vita­min D.

Perhaps more interestingly, they warned that more than 2,000 mg of calcium per day increases the risk of kidney stones. Likewise, very high levels of vitamin D (above 10,000 IU per day) are known to cause kidney and tissue damage.

So at the risk of upsetting the vitamin industry, we’ve decided to save our money and our kidneys. From now on we’ll be getting our daily requirements of calcium and vitamin D by drinking milkshakes in the sun!