Solutions set in stone: an innovative, nutrition-based approach to managing kidney stones

The biotechnology company Captozyme is spearheading an innovative approach to nutrition to prevent the formation of painful kidney stones and other complications arising from the absorption of calcium oxalate from food. The company’s research efforts are led by Dr Qing-Shan Li, co-founder and CSO of the company.

Oxalate, a plant-based dietary substance with no known positive effects on the human body, is responsible for several debilitating health problems. These include the painful condition known as kidney stones. Dr Qing-Shan Li and associates at the biotechnology company Captozyme (www.captozyme.com) are dedicated to the prevention and treatment of these problems.

Oxalate: the anti-hero

Oxalate can be present in high concentrations in many plant foods, including rhubarb, beets, okra, spinach, sweet potatoes, nuts, beans, tea, chocolate, and soy products. It is, therefore, a common component of the average Western diet. Up to approximately 25 percent of the oxalate consumed in the diet is absorbed into the human bloodstream through the intestines. The unabsorbed oxalate can chelate (bind to) the dietary nutrients magnesium, iron and calcium, both in food and in the gastrointestinal tract, forming salts with these elements and limiting their bioavailability in the body. Thus, oxalate can, effectively, be described as an anti-nutrient: a substance that works against the nutritional value of food by rendering certain nutrients unattainable.

The formation of calcium oxalate kidney stones
Dietary oxalate can become actively harmful when too much of it is absorbed; oxalate is a component of the most common type of kidney stone. As an illustration, approximately 75% of all kidney stones in patients in the United States consist of calcium oxalate. It is estimated that 1 in 11 adults in industrialised countries will develop a kidney stone, and preventative measures employed to date are of limited efficacy.

A graphical rendering of one type of oxalate-degrading enzyme; oxalate decarboxylase or OxDC. Captozyme specialises in oxalate-degrading enzymes but their research programmes also include other enzymes for a different set of sensitivities and ailments.

Kidney stones arise from an excessive urinary excretion of oxalate, or hyperoxaluria. Hyperoxaluria has two sub-types, primary hyperoxaluria and secondary hyperoxaluria, which differ in their pathogenesis, severity of clinical presentation, and treatment plan. However, both disorders can cause recurrent kidney stones, nephrocalcinosis, and end-stage renal disease, and for primary hyperoxaluria there is no existing treatment. Oxalate can also cause complications in patients who have inflammatory bowel disease (IBD) and short-bowel syndrome.

People consuming typical Western diets tend to have a serum oxalate concentration that is much lower than the saturation concentration (the point at which it will start to solidify out of the solution). However, water re-absorption in the kidney concentrates oxalate in urine by more than 100 times, with the result that urinary calcium oxalate is often supersaturated. Calcium oxalate supersaturation is thought to be the primary cause of the formation of calcium oxalate stones, but the process is complex, not well understood, and may involve a number of critical factors. Reducing the ingestion of oxalate can keep the concentration in urine below the point at which it starts to solidify and therefore prevent the formation of an abnormal level of calcium oxalate precipitate.

Captozyme has taken the innovative approach of reducing the oxalate concentration in food through adding an oxalate-degrading enzyme.

Existing treatments and therapies
Humans do not naturally produce enzymes to break down oxalate and so a combination of lifestyle changes and medication is the usual approach to preventing kidney stones. Doctors may recommend that patients drink water throughout the day to produce more urine and flush calcium oxalate out of their systems. Reducing both salt intake and consumption of animal protein, promoting oxalate excretion through increased calcium intake, increasing urine alkalinity, and avoiding dietary oxalate ingestion are also typical methods for reducing the chances of developing calcium oxalate kidney stones and other oxalate-related conditions.

However, as oxalate is contained in many different foods, often at different levels in a single food, avoiding oxalate consumption while maintaining a balanced diet is difficult. Moreover, available therapies do not address the formation of calcium oxalate within the body. Captozyme has addressed these problems, taking the innovative approach of using oxalate-degrading enzymes to remove oxalate in the digestive tract and to reduce the oxalate concentration in food. Their approach tackles oxalate absorption at the first possible moment.

Limiting the flow
Captozyme has developed enzyme products that degrade oxalate, thereby promoting its removal from both the diet and the body. These enzymes can act throughout the gastro-intestinal tract, from the stomach to the large intestine. Cz2294, is an oxalate-degrading enzyme that is highly stable in acid environments and can remove oxalate in the stomach. In contrast, the enzyme Cz1408 removes oxalate throughout the intestine. This combination means that oxalate is removed throughout the digestive system, thereby limiting the amount of oxalate that is absorbed in the intestines and reducing the risk of kidney stones without compromising nutritional requirements.

Straight to the source
In addition, Captozyme’s enzymes can be used in a range of food products to remove oxalate from food and beverages before packaging. This processing would degrade the oxalate present in the food, unlocking the potential of the iron, calcium, and magnesium within the regular diet and avoiding the need for dietary restrictions. Captozyme is also poised to introduce a supplement to address oxalate sensitivity and is developing its proprietary enzymes as stand-alone therapeutics for the treatment of more severe diseases caused by oxalate. These enzymes are the culmination of almost a decade’s worth of funded research, testing and refinement.

Philosophy for success
In addition to developing its enzymatic oxalate-degrading products, Captozyme seeks to build on growing positive consumer behaviour towards food and nutrition by providing education about anti-nutrients and simple personal nutrition solutions. Unlike those requiring a gluten-free or lactose-free diet, Captozyme regards the oxalate-sensitive population as having been ‘completely underrepresented’ by specialty foods and is determined to address this.

The success of Captozyme’s approach in applying research to commercial opportunities exemplifies how the support currently given to small businesses leads to innovative solutions and commercial success.

Credit for main image: Image of kidney stones by Kempf EK via Wikimedia Commons https://creativecommons.org/licenses/by-sa/3.0/