One step closer to solving kidney stones

Izelle Theunissen, MRC News

Kidney stones are a painful reality many people have to live with. But they are also very expensive - with an estimated annual cost to the country of R80 million. Fortunately, Prof. Allen Rodgers, an MRC-supported researcher at the University of Cape Town, is one step closer to solving the problem.  Kidney stones are a world-wide problem, with 10-15 % of the general population being affected. Crystals - of which calcium oxalate is the most common - form in the urine and then progress through the spaghetti-thin tubes of the urinary tract, resulting in intense pain. The phenomenon has been baffling scientists for many years, with no one being able to pinpoint the exact reason for crystal formation.  The black and white case Prof. Allen Rodgers from the Department of Chemistry at UCT describes his research as applied clinical chemistry. He's basing research on the well-known observation that black people are immune towards kidney stone disease. Prof. Rodgers is interested in proteins which occur in urine and is collaborating with Dr Ed Sturrock of the Dept of Medical Biochemistry in this research. 

"We know that one such protein, called prothrombin fragment 1, inhibits calcium oxalate crystals from forming. So we've based our efforts on the hypothesis that the prothrombin protein in the urine of black people may have a more powerful inhibitory effect than the protein in the urine of white people," Prof. Rodgers explains.

The research team isolated the prothrombin fragment from both groups, and then tried to grow calcium oxalate crystals in the presence of the respective prothrombin fragment isolates. 

So far, their hypothesis has proven correct. "Our results showed that both urine extracts exert an inhibitory effect (which was what we expected), but that the extract from the urine of the black subjects was far more effective in preventing calcium oxalate crystals from forming," he says. 

The results have interesting consequences. "The implication of these results is that the protein in the urine of black South Africans may eventually lead to a prophylactic preparation to prevent kidney stone disease. If we, for example, find that the protein is the key, we would like to find a conservative way of increasing that protein in the body. Or, alternatively, finding what factors of the structure of the protein confers its protective abilities, could help to make a such a protective preparation," Prof. Rodgers predicts.

A further research project in the laboratory is investigating another urinary protein called Tamm Horsfall glycoprotein. "But it is very challenging work, because the properties of the protein depend on many variables. For example, the concentration of citrate in the urine can influence the way the protein behaves," he says.  Dietary oxalate absorption Another research project in Prof. Rodger's laboratory is investigating the absorption of dietary oxalate. Two groups of volunteers (one group being black people and another group white) are given diets containing food rich in oxalate such as spinach, rhubarb and beetroot. This is done under strict supervision of a qualified dietician.

According to Prof. Rodgers, this is done to increase the oxalate content of the urine, because the higher the oxalate concentration, the higher the risk of developing calcium oxalate crystals.

The results have once again been very interesting, with the black study subjects absorbing the dietary oxalate to a lesser extent than the white subjects. "This confirms the role that oxalate plays in stone formation. If the absorption of this chemical can be decreased in some way, then the risk of kidney stone formation will be significantly decreased," Prof. Rodgers explains. Multidisciplinarity  Prof. Rodgers finds this field of research very exciting, because it's multidisciplinary. "We work with scientists from a wide range of backgrounds. At any kidney stone conference, you will find a divergent group of people presenting papers. You'll find basic scientists (for example physical chemists, biochemists and organic chemists), and you'll also find urologists, nephrologists, chemical engineers (who build flow systems to simulate the urinary tract), and even computer programmers who write programmes to mimic crystal formation," he says.

"My own philosophy in any field of research is that if it's multidisciplinary, with everybody offering something from their field of expertise, then you'll find something meaningful. So we look to collaborate very widely," he closes.

Courtesy of the  MRC News.

More Information:

If you want to know more about Prof. Rodger's work, please contact him at tel.: (021) 650-2572 or e-mail: allenr@science.uct.ac.za

 

November 2001