Kidney stones: the holy grail of dissolution

APPROXIMATELY one in 10 Australians suffer from kidney stones, but local data on prevalence, incidence and prevention is thin on the ground, leading Australian experts to call for new research comparing standards of care in this country.

Up to 50% of people with a first presentation of kidney stones will have a recurrence within 5 years, despite the gold standard, three-pronged prevention methods of increased fluid intake; high-calcium, low-salt, low-protein diet; and daily medications remaining unchanged since the turn of the century.

Now, research published in Nature has flagged a possible new entry in the prevention stakes, renewing interest in the “holy grail” of stone dissolution.

Researchers at the University of Houston in the US have found evidence that a natural fruit extract, called hydroxycitrate (HCA), is capable of dissolving calcium oxalate crystals – the most common component of human kidney stones – and may be more effective than the preferred therapy of potassium citrate (CA).

The researchers used atomic force microscopy to study interactions between the crystals and HCA under realistic growth conditions. This technique allowed them to record crystal growth in real time.

HCA is found in a variety of tropical plants including Garcinia cambogia and Hibiscus subdariffa. It is listed on the Australian Register of Therapeutic Goods and has primarily been marketed for weight loss management and metabolic health.

Dr Finlay Macneil, a urologist and conjoint senior lecturer at the University of Newcastle’s School of Medicine and Public Health, said that the US research findings were very exciting, but cautioned that translating the results into real-world treatment would be difficult.

“It’s a question of what we can achieve with what is readily available and doesn’t cost the Earth,” Dr Macneil told MJA InSight.

“The interesting point of this research is that HCA is shown in vitro to be a more potent inhibitor of calcium oxalate crystal formation than CA, as well as showing evidence of dissolution of these calcium oxalate crystals, even at concentrations of one thousandth of the calcium concentration.

“The problem is the applicability to the clinical setting.

“Perhaps the most telling [aspect of] the article is that dissolution activity is only seen in a narrow range of concentrations of HCA. It is notoriously difficult to achieve a specific concentration of any compound in the urine, so the clinical application of this discovery may prove difficult.

“On the positive side, HCA is readily available as Garcinia, currently marketed as a dietary supplement for weight loss in Australia.

“What is needed is a randomised trial of a dietary supplement of HCA on stones not causing problems to determine if dissolution occurs, and on recurrent calcium oxalate stone formers to determine if the stone formation rate is altered by a clinically significant rate.”

The lack of local research into the prevention of kidney stones was “surprising”, said Dr Martin Fedderson, a nephrologist in Gosford, NSW.

“The burden of disease is clearly high with health care costs, which are substantial when the treatment surrounding this condition is considered,” Dr Fedderson told MJA InSight.

“I’m surprised that there is little literature on this and few pharma companies keen on tackling this.

“Lifestyle changes and compliance [with preventive medication] remains challenging, but may be improved if there is a promise of dissolving these stones.

“The cost of CA is currently a huge barrier for patients, especially when they realise that only a urologist can get rid of existing stones.

“Low citrate levels are seen in a small population of patients, commonly those with renal tubular acidosis. Correcting this with CA is often very challenging.”

Dr Uri Hanegbi, a urologist in private practice in Melbourne, told MJA InSight that recurrence rates in patients with kidney stones were “not very good” with only about 5% of patients using any preventive methods.

“The average stone patient knows that it may be 5 or 10 years until he gets a recurrence, so the prospect of taking medication every day for the rest of his life just to halve the risk of recurrence isn’t very appealing, and most won’t take it,” he said.

The prospect of a new treatment possibility in the form of HCA was more attractive, he said.

“It would still mean taking medication forever, but it would be nice if it was natural, cheap and made recurrence rates much lower.”

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