Ground-breaking discoveries relating to the formation of kidney stones

Apr 14 2004

Ground-breaking discoveries relating to the formation of kidney stones have earned Flinders University researchers a grant of more than $1.2 million (Australian) from the National Institutes of Health (NIH), the major funding body for medical science in the United States.

Funding over five years has been awarded to a research project led by Professor Rosemary Ryall, professor of urological research in the University's Department of Surgery. Other members of the research team include Miss Magali Chauvet, Dr Phulwinder Grover, Dr Damian Hussey, Dr Alan Stapleton and Professor Villis Marshall.

US funding for Australian research is comparatively rare, and this is only the second time that research at Flinders has attracted a grant from the NIH. Professor Ryall said insoluble crystals of calcium oxalate, the dominant component of kidney stones, precipitate in everyone's urine from time to time, but normally are excreted harmlessly away.

Occasionally the process goes wrong, resulting in kidney stones. Up to ten per cent of the population are affected by kidney stones. Their ability to block vessels in the kidneys and the urogenital tract is seldom life-threatening, but often generates excruciating and debilitating pain.

"People mistakenly think that the pain of a kidney stone is caused by its passage, but the pain is actually caused when it blocks the ureter, and causes back pressure on the kidney," Professor Ryall said.

In rare instances, a kidney can be ruptured as a result.

"If combined with infection, the result is catastrophic: obstruction and infection can kill a kidney in 24 hours," Professor Ryall said.

While kidney stones do not often kill people, they are expensive to treat, Professor Ryall said. In 1993, for instance, the cost of kidney stones to the public in the US was estimated at two billion dollars.

The research at Flinders will investigate the basic mechanisms involved in crystal formation, and particularly the role of proteins.

The bulk of a kidney stone is crystalline, but Professor Ryall said that dissolving away the mineral reveals the presence of organic material, which is mainly protein.

"We are interested in how the proteins affect crystal formation, and particularly how they may make the crystals more susceptible to being disposed of in the body," she said.

Professor Ryall's research over the past five years has discovered a startling phenomenon that may shed new light on the body's disposal mechanisms.

"We have established that when the crystals form in the urine, they have proteins inside them," Professor Ryall said. While there had been some initial scientific scepticism about the finding, she said the evidence is now overwhelming.

The presence of the proteins is thought to encourage the action of proteases, the enzymes employed by the body to convert inactive proteins to an active form, or to break down unwanted proteins.

"If you have a mineral that has proteins all through it and a protease worms its way inside to eat away at the proteins, it obviously helps to break down the crystal structure," Professor Ryall said.

The NIH funding will enable this hypothesis to be tested. For the past two years, the cost of the research at Flinders has been sustained by the award of the Bruce Pearson Fellowship from the Australian Urological Foundation.

The new funds from the US will enable research in the laboratory to be conducted with an expanded research staff, alongside a small component of clinical work. In discovering more about the basic mechanisms of crystalline accretion, the research has the potential to develop improved clinical treatment for sufferers of kidney stones.

Possibilities for the research don't stop there, and the team has already established collaborative links with nanotechnologists at Flinders.

"It has implications for all sorts of things," Professor Ryall said.

"If you can change the structure of a mineral by putting proteins inside it or by filling it with holes, there are all sorts of potential applications for industry in areas like ceramics."