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Dissolving Kidney Stones Research Paper

Anyone who has suffered from kidney stones is keenly aware of the lack of drugs to treat the condition, which often causes excruciating pain.

A new mouse study, however, suggests that a class of drugs approved to treat leukemia and epilepsy also may be effective against kidney stones, researchers at Washington University School of Medicine in St. Louis report.

The drugs are histone deacetylase inhibitors, or HDAC inhibitors for short. The researchers found that two of them — Vorinostat and trichostatin A — lower levels of calcium and magnesium in the urine. Both calcium and magnesium are key components of kidney stones.

The research is available online in the Journal of the American Society of Nephrology.

“We’re hopeful this class of drugs can dissolve kidney stones because its effects on reducing calcium and magnesium are exclusive to kidney cells,” said senior author Jianghui Hou, PhD, assistant professor of medicine. “In the mice, we achieved dramatic effects at a fraction of the dosage used to treat leukemia and without significant side effects.”

Most kidney stones form when the urine becomes too concentrated, allowing calcium and magnesium to crystallize and stick together. Intense pain develops when stones get stuck in the urinary tract and block the flow of urine.

Diet can play a role in the condition. Not drinking enough water or eating a diet with too much salt, which promotes calcium to be released into the urine, increases the risk of stones. Some people also are genetically prone to developing kidney stones, and they naturally release too much calcium into the urine.

Typically, doctors recommend drinking lots of water to help pass kidney stones from the body. Thiazide, a type of drug used to treat high blood pressure, sometimes is prescribed to treat the stones because it reduces calcium in the urine. But the drug also increases magnesium in urine, countering its effectiveness against kidney stones.

In the new study, Hou and his colleagues showed that Vorinostat, approved to treat leukemia and epilepsy, and trichostatin A, an antifungal drug, mimic a natural process in the kidney that reabsorbs calcium and magnesium into the urine.

Kidneys, in addition to filtering waste from the blood into the urine, also play an essential role in reclaiming minerals that the body needs to carry out basic functions of life. Normally, some calcium and magnesium in the blood are filtered into the urine and then reabsorbed back into the blood, depending on the body’s need for these essential minerals.

Hou’s earlier work showed this process is heavily dependent on the activity of a gene called claudin-14. When the activity of claudin-14 is idled, the kidney’s filtering system works like it’s supposed to. But when the gene is activated, calcium and magnesium are blocked from re-entering the blood.

The gene’s expression is controlled by two snippets of RNA, a sister molecule of DNA, Hou’s previous research has shown.

As part of the new study, Hou and his colleagues found that Vorinostat and trichostatin A do not act directly on the claudin-14 but mimic these so-called micro-RNA molecules, keeping the activity of the gene in check. That the drugs can modify the activity of micro-RNAs make them attractive as potential treatments for kidney stones.

In the mice, small doses of Vorinostat, for example, reduced calcium levels in the urine by more than 50 percent and magnesium levels by more than 40 percent. Similar results were noted for trichostatin A.

“Kidney cells were very sensitive to the drug,” Hou explained. “We used one-twentieth of the dose typically used in humans and achieved significant results. We now want to test the drug in clinical trials for patients with kidney stones.”

Mice don’t develop kidney stones, so it will be important to test the drugs against kidney stones in patients, but the current study provides proof of principle that HDAC inhibitors regulate the same pathway that leads to kidney stones, he said.


The research was supported by the National Institutes of Health (NIH), (R01-DK084059 and P30-DK079333) and the American Heart Association (0930050N).

Gong Y, Himmerkus N, Plain A, Bleich M and Hou J. Epigenetic regulation of microRNAs for controlling CLDN14 expression as a mechanism for renal calcium handling. Journal of the American Society of Nephrology. July 30, 2014.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

By Anna Zisman, M.D.

The featured imagepoints to a widespread idea now on the web concerning how cola drinks might promote kidney stone passage. It has been called the ‘Coke Treatment for Kidney Stones.‘ Fluids are valuable for all stone formers, but the suggested usage may not be ideal and this post points out some of the drawbacks.

OUR PATIENT

A few months ago, a delightful 71-year-old woman presented to our clinic for a metabolic evaluation to try to stop her chronic kidney stones. She passed her first kidney stone about 5 years ago. A year later she developed another kidney stone, which required shockwave lithotripsy therapy. Ultimately her stone was analyzed and she was told it was a “calcium stone.” Over the following few years, she continued to pass one stone per year. More recently, the frequency had increased to a few times per year. Frustrated with the frequent stone recurrences, she sought information online regarding potential remedies for recurrent stone disease. On several websites she came across a remedy known as the “Coke treatment,” which was purported to dissolve kidney stones and prevent stone recurrence. She sent in her payment of $39.97 and received a booklet instructing her to do the following:

  • drink 72 ounces of Coca Cola, ideally not diet or caffeine-free, in 15 minutes or as fast as possible
  • steam and puree one-half pound of asparagus and drink immediately
  • repeat as necessary until kidney stone pain is resolved and stones have passed
  • some variations of this treatment that can be found on the web also recommend drinking water for several hours after the treatment

She dutifully followed the instructions provided and found that on the day of her acute pain, her symptoms did, indeed, abate. Unfortunately, over the next year she found the frequency of her stone attacks actually increased – most recently to as often as passing gravel 2 to 3 times weekly (with significant discomfort). To combat this she has been using the “Coke treatment” about 2-3 times weekly over the last year, creating an apparent vicious cycle (more on that later). Finally, her daughter insisted that she see a physician and so she presented to our office, wondering why her treatment hasn’t been effective.

THE COKE TREATMENT IS COMMON ON THE NET

Using the term ‘Coke treatment of kidney stones’ yielded about 108,000 results, and by page 10 the treatment was still prominent. So cola drinks as a treatment is current.

claim in Internet lore is that phosphoric acid, an additive used in dark colas, when consumed in large quantities can facilitate a reaction within the kidney that will dissolve the calcium oxalate or calcium phosphate admixture that is the kidney stone.  One finds variants of this claim in the discussions by patients.

As I pictured this poor older woman chugging a 6-pack of Coke 2-3 times per week with an asparagus chaser, I was curious to determine whether any potential scientific merit to the internet solution exists.

In short, the answer is No.

Allow me take you through some of the details.

THE EVIDENCE FOR COKE

Fluids are Useful

I will start with the 72-ounces of Coca Cola that are to be ingested rapidly. Of course, if one is having acute renal colic with a small stone stuck in a tiny structure like the ureter or urethra, drinking over two liter of fluids of any sort is likely to be beneficial in attempting to propel the stone forward and out of the body. But why Coca Cola? Or any cola for that matter? Is there some reason to believe cola drinks have special properties as a stone treatment?

As far as I can tell, no.

Cola Drinks Are Not a Proven Remedy

Phosphoric Acid as a Stone Dissolver

Phosphoric acid, mixed with nitric acid, is used as a cleaner in the beer industry to remove beerstone (calcium oxalate) from beer kegs. It is also used in home cleaning solutions, as an industrial etchant, and as a rust remover. This leads to the false impression that drinking acid phosphates in beverages will create conditions in the kidneys like those in the beer kegs.

In beer kegs, and when you clean your floor with cleaners, high concentrations of a strong acid are applied directly to the unwanted material.

You Can’t Get Phosphoric Acid into the Urine

But when the small quantities of phosphoric acid found in dark colas are ingested, the first thing that will happen is that calcium and magnesium binding will occur in the gastrointestinal tract. By the time the remaining phosphoric acid is absorbed, additional buffering will occur in the blood and bone, so essentially neutral – not acid – phosphate will be delivered to site of the stone. In studies of a neutral phosphate’s effect on crystal inhibition and dissolution, no evidence of crystal dissolution has been noted.

Effects of Cola in People

How about real people, instead of crystals?

Cola Drinks Raise Stone Risk in Urine

Four subjects were asked to drink three quarts (96 oz) of a dark cola over the course of 48 hours. The researchers then compared the amounts of 3 urine constituents that are known to affect the likelihood of stone formation: magnesium (higher levels in the urine are associated with DECREASED likelihood of stone formation), citrate (higher levels are associated with DECREASED likelihood of stone formation) and oxalate (higher levels are associated with INCREASED likelihood of stone formation). In this study, the average 24-hr magnesium excretion decreased by 2.6 mg, the average citrate excretion decreased by 122 mg, and the average oxalate excretion increased by 8.6 mg.  So in fact, in each of the three constituents, the effect of the cola was a worsening of stone risk.

A larger study performed a few years later confirmed these findings, as well as an associated increase in supersaturation for calcium oxalate in a group of 45 subjects.

Cola Drinks Raise Statistical Risk of Stones

In nearly 200,000 individuals who have been followed over time, Ferraro and colleagues analysed the association between consumption of sugar-sweetened colas and kidney stone formation. Subjects consuming the most sugar sweetened colas were 23% more likely to develop a kidney stone than those in the lowest consumption group. In general cola type drinks are exactly the wrong ones for stone prevention.

Cola Drinks May Pose Other Health Hazards

Sugar and Sodium

The suggested amount of regular Coke in the ‘Coke treatment’ has 840 calories, 270 mg of sodium, and 39 grams of sugar. Taking in that many calories from sugar will almost certainly reduce the amount of other nutrients that one is able to eat or drink in a day, while sugar and sodium are both directly linked to higher urine calcium excretion, a key contributor to nephrolithiasis.

Bone Disease

Whether because of substitution for milk-based drinks, or due to the high acidity associated with soft drinks, consumption of increasing quantities of carbonated beverages has been linked to osteoporosis.

Kidney Disease

In addition to the well known association with diabetes and obesity, a recent report has linked higher consumption of dark colas (2 cans or more per day) with risk of chronic kidney disease.

WHAT ABOUT ASPARAGUS?

Ancient Beliefs

Asparagus has been cultivated in the Mediterranean region and in Asia for over 2000 years. Egyptians, Greeks, and Romans believed asparagus to have medicinal properties ranging from treating mood disorders to rheumatism, and a 15th century Arabic sex manual entitled “The Perfumed Garden” claimed asparagus has aphrodisiac properties. It is believed by many to have diuretic properties.

Not Our Asparagus

The usual variety of asparagus that we would buy at the store, Asparagusofficinales, is a different species than the medicinal Asparagus racemosa, which is commonly grown in Asia. Furthermore, the medicinal use of asparagus typically involves the root, not the shoot that we typically eat. In Germany, for example, asparagus root is approved by an herbal oversight board as a diuretic whereas the shoot is not recommended.

Not Any Asparagus?

How good is the evidence? Despite what the herbal board says, arecent review found no evidence for human use of the asparagus root as a diuretic. And what if it were a potent diuretic, for argument’s sake? It would have to have specific effects in the distal convoluted segment (a particular region of the kidney tubule), like the thiazide diuretics, to have any beneficial effects on stone prevention –and certainly unlikely to be effective in the acute setting.

So What’s the Harm in a Lot of Asparagus? 

Generally, not much. In normal quantities it is  a healthy vegetable loaded with nutrients such as folate, potassium, and vitamin C. For a stone former, however, there may be hidden dangers with a high asparagus intake. Asparagus has a moderate amount of oxalate, and this amount adds up quickly with repeated administrations of such treatments as the ‘Coke treatment.’ Furthermore, vitamin C is also metabolized to oxalate in the body, adding more of the lithogenic substance to the urine. So, as with most things (except water), it seems that moderation is key.

OUR PATIENT

Looking back,our patient appears to have increased her stone attack frequency with the help of the “Coke treatment” from yearly to several times per week. It seems that the remedy was indeed worse than the disease.

During our visit, in preparation for which she performed several 24-hour urine collections, we determined an individualized plan for her kidney stone treatment based on her urine parameters and a thorough history. With a steady increase in her daily fluid intake and the addition of thiazide therapy, at last check she has had no further stone episodes.

OUR FINAL WORD ON THE ‘COKE TREATMENT’

On a hot Summer day, a can of Coke can be delightful. As a medical treatment for kidney stones, no cola is as good as plain water. In the very high doses of the ‘Coke treatment’ there is no benefit predicted from what science we have, and no data to show benefit from a clinical trial. In fact, it would be difficult to organize and perform a clinical trial of the ‘Coke treatment’ because of its evident potential for harm. The trial would be unlikely to pass the human subject protection board review.

Don’t do it.

You Might Want to Read:

Kidney Stone Pain

Fluids to Prevent Stones

Citrate to Prevent Stones

What Stones Are

Types of Kidney Stones

 

 

 

 

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