Kidney stones are small, hard deposits of crystals that form in the kidney. They occur in up to twelve per cent of men and seven per cent of women – with tendency rising. Risk factors include high blood pressure, diabetes and obesity. Once a kidney stone has occurred, the probability of a recurrence is 60 percent. Complications can occur as the stone wanders into the ureter, where it leads to a renal colic, and is associated with severe pain, blood in the urine and the risk of kidney damage.
Over the past 30 years, the approach for the prevention of kidney stones has hardly changed. Doctors recommend that patients carrying an increased risk mostly drink a lot and avoid oxalate containing foods. This is because the majority of kidney stones – about 65 percent – are made up of calcium oxalate. The list of oxalate rich foods includes rhubarb, okra, spinach, beets and almonds, as well as chocolate, coffee and black tea.
Another suggestion is to consume citrate (CA) in the form of potassium citrate, which can delay the crystal growth. This is presented by a recent review, whereby potassium can prevent the formation of kidney stones, and reduce the size of the stones. However, side effects are described – mainly as disorders of the upper digestive tract. About 16 percent of patients cease taking it due to side effects. Furthermore, intake of potassium citrate means the risk of hyperkalemia becomes a matter of concern.
Natural fruit extract dissolves crystals
Now a team of researchers has discovered a possible alternative medication to potassium citrate. Scientists led by Jeffrey Rimer of the Faculty of Chemical and Biomolecular Technology at the University of Houston (USA) were the first to show that the chemical compound hydroxycitrate, or hydroxycitric acid (HCA), effectively inhibits the growth of calcium oxalate crystals – and even dissolves them under certain conditions. This discovery could help in developing new strategies for the prevention of kidney stones, the researchers report in the journal Nature. The study also involved employees from the company Litholink, which is developing and offering urine tests for the diagnosis of urinary stones.
Hydroxycitrate is chemically related to potassium citrate. It is a natural fruit extract and is also available as a dietary supplement. In their study Rimer and his colleagues compared the two substances using various methods. First, using atomic force microscopy they analysed the growth of calcium oxalate crystals under real world conditions. Using this process crystal growth was able to be observed in real time at an almost molecular level. In their analyses, the researchers observed that the crystals shrank at certain concentrations of HCA. Rimer held this observation to be an initial measurement error because crystals do not normally dissolve in a highly supersaturated solution. Nevertheless further tests showed the original result to be correct.
HCA binds more strongly to the crystal surface than does CA
In the next step, the scientists analysed the causes of this process. With the help of density functional theory (DFT), they investigated how HCA and CA bind to calcium and calcium oxalate crystals. DFT is a highly accurate computer-based method through which the structure and properties of materials are able to be analysed. The calculations showed that HCA correlates to a stronger bond with the crystal surface than does CA, thus a voltage is generated which apparently leads to the dissolving of calcium and oxalate ions. This process eventually leads to the dissolution of the crystals.
Finally Rimer and his team tested seven healthy subjects without kidney stones to see whether HCA is excreted from the urine – a requirement in order to use it as a pharmaceutical agent. The participants took the substance for three days in a standard dose. It turns out therein that a significant amount of HCA is excreted in the urine.
Human studies necessary
“Our initial results are promising and provide the basis to develop a new, effective pharmaceutical agent for the prevention of kidney stones”, says Rimer. “If the dissolution process of the crystals functions in humans as it does in our laboratory tests, HCA has a great potential to reduce the occurrence of kidney stones and chronic kidney stone disease”.
Since hydroxycitrate functions with more potency than does potassium citrate, it could be the preferred substance for the prevention of kidney stones in the future. In addition, it could be more suitable for patients who have alkaline urine. This is because potassium citrate increases the pH levels of urine, favouring the formation of calcium phosphate stones – another type of kidney stones.
Nonetheless, many questions, which would have to be answered through further studies, remain open, stresses Rimer: the effectiveness of HCA needs to be studied in clinical trials; a suitable dose needs to be found and the long-term safety of the active agent checked. Currently HCA is available as an appetite suppressant in capsule form. However, its exact mode of effect has not yet been scientifically studied.