Anyone who's ever had kidney stones can tell you how horribly painful the experience can be. Unfortunately, preventative treatment has not changed much in the last three decades. But researchers are proposing a new treatment that could dissolve calcium oxalate stones and spell relief for those who are sidelined by these small, hard mineral deposits.
There are different types of kidney stones, of which calcium oxalate crystals are the most common in humans. They affect men and women and, the Mayo Clinic explains, they have no definite, single cause although people who are hypertensive, have diabetes or are obese have a higher risk of developing kidney stones.
The best way to deal with kidney stones is to avoid them, and you do that by drinking plenty of water and avoiding foods rich in oxalate, such as rhubarb, okra, spinach and almonds. Sometimes doctors recommend taking citrate (CA) — in the form of potassium citrate — a supplement that can slow crystal growth. But some people are unable to tolerate the side effects.
Prevention is great and all, but what happens if you end up doubled over with kidney stones anyway?
Once you're down for the count, it's a question of coordinating with your doctor, drinking a lot of water and waiting for them to pass. Depending on the severity of pain, your doctor may prescribe a NSAID, and in rare occasions where the stones are too large to pass, surgery may be required.
Researchers wanted to find a treatment for the most common type of kidney stone that would work like citrate but without the associated side effects. They found evidence that a natural fruit extract is capable of dissolving calcium oxalate crystals.
Jeffrey Rimer, associate professor of chemical engineering at the University of Houston, was lead author of the study, published this week in the online edition of Nature. The work shows how the compound hydroxycitrate (HCA) is an effective inhibitor of calcium oxalate crystal growth that, under certain conditions, is actually able to dissolve these crystals.
The findings are the result of a combination of experimental studies, computational studies and human studies, Rimer said.
The project grew out of preliminary work done by collaborator John Asplin, a nephrologist at Litholink Corporation, who suggested HCA as a possible treatment. HCA is a derivative of citric acid that is found in a variety of tropical plants, such as Garcinia cambogia, which is, in turn, better known by many names, including Malabar tamarind or brindleberry, and is available as a dietary supplement. The fruit looks like a small pumpkin and ranges in color from yellow to light orange to green.
The head-to-head studies of CA and HCA determined that while both compounds inhibit the growth of calcium oxalate crystals, HCA was more potent and displayed unique qualities that are advantageous for the development of new therapies.
The team of researchers then used atomic force microscopy, or AFM, to study interactions between the crystals, CA and HCA under realistic growth conditions. According to Rimer, the technique allowed them to record crystal growth in real time with near-molecular resolution.
One of the researchers noted that the AFM images recorded the crystal actually shrinking when exposed to specific concentrations of HCA. Rimer suspected the initial finding was an abnormality, as it is rare to see a crystal actually dissolve in highly supersaturated growth solutions. The most effective inhibitors reported in the literature simply stop the crystal from growing.
It turned out that the initial finding was correct. Once the team confirmed the possibility of dissolving crystals in supersaturated solutions, it focused on trying to determine why.
The researchers applied density functional theory (DFT) — a highly accurate computational method used to study the structure and properties of materials — to address how HCA and CA bind to calcium and to calcium oxalate crystals. They discovered HCA formed a stronger bond with crystal surfaces, inducing a strain that is seemingly relieved by the release of calcium and oxalate, leading to crystal dissolution.
HCA was also tested in human subjects. Seven people took the supplement for three days, allowing researchers to determine that HCA is excreted through urine, a requirement for the supplement to work as a treatment.
While Rimer said the research established the groundwork to design an effective drug, questions remain. Long-term safety, dosage and additional human trials are needed, he said.
"But our initial findings are very promising," he said. "If it works in vivo, similar to our trials in the laboratory, HCA has the potential to reduce the incidence rate of people with chronic kidney stone disease."