The National Institute of Diabetes and Digestive and Kidney Diseases has renewed a major grant which will allow Indiana University School of Medicine researchers to continue scrutinizing the long-term effects of shock wave lithotripsy in the treatment of kidney stones.
Andrew P. Evan, Ph.D., professor of anatomy, is the principal investigator of the $6.5 million grant. This is the third time the NIDDK has funded the novel research; first in 1994 with $2.45 million and again in 1998 when it received $4.15 million in grant funding. The money will finance four different projects, all ultimately seeking to improve the effectiveness and safety of shock wave lithotripsy.
Early studies by the IU School of Medicine researchers and others in the field have proven that lithotripsy treatments cause tissue damage with potential long-term health consequences.
"In our previous grants, we were looking for mechanisms that cause shock waves to break stones and injure tissue," said Dr. Evan. "We have spent nine years on that and have made very good progress in answering those questions. Now, we're reviewing the data to develop protocols to make lithotripsy safer for all patients."
Dr. Evan, Lynn Willis, Ph.D., professor of pharmacology and toxicology and of medicine, and James E. Lingeman, M.D., volunteer clinical professor of urology, are seeking ways to protect a kidney from the tissue damage that occurs with a clinical dose of shock waves.
The group previously developed a pre-treatment protocol to reduce tissue damage from shock wave lithotripsy. During the treatment, blood vessels break and internal bleeding develops in the kidney. Drs. Evan, Willis and Lingeman determined that administrating 100 to 500 low-level shock wave doses allows the blood vessels to constrict more rapidly, thus protecting the kidney and reducing internal bleeding before a clinical dose of shock wave is administered.
Current grant funding will allow the researchers to try to determine the physiological mechanisms causing the blood vessel constriction. That information will help the researchers to further refine the protocol and begin a clinical trial, which may revamp standard shock wave lithotripsy protocols or lead to the development of drugs that can enhance the constriction to reduce the number of shocks administered.
The IU shock wave lithotripsy research team is an independent test site for the new generation of lithotriptors manufactured in the United States, Israel and China.
In another area of the research, scientists already learned that the slower the rate of shock waves, the better the kidney stones break. This reduces the number of shocks administered per minute for each patient and this protocol currently is being tested in clinical patient trials.
James A. McAteer, Ph.D., professor of anatomy and cell biology, is the principal investigator of this portion of the grant project. He and James C. Williams Jr., Ph.D., associate professor of anatomy and cell biology, know there is a direct correlation between the number of shocks administered and the amount of tissue damage incurred. They will test how well stones break with the new lithotriptors to determine which is safest for patients.
University of Washington physicist Larry Crum, Ph.D., principal investigator for this grant project with Michael Bailey, Ph.D., and Boston University engineering professor Robin Cleveland, Ph.D., are focused on developing mathematical models of how kidney stones break. With the current grant funding, they will develop ways to better image the stone and follow it through the treatment process.
As with the other projects, Drs. Crum, Bailey and Cleveland are intent on reducing the number of shocks needed to treat patients effectively. When patients breathe, the action causes kidney stones to move. They want to develop a model to control when the shock wave fires so it will only fire when the stone is in its pathway.
A final theoretical arm included in the program project grant funding is under the direction of Tim Colonus, Ph.D., a professor of aeronautics at California Institute of Technology. Dr. Colonus and his team have developed a sophisticated computer model of air bubbles generated when shock waves travel through the water to the kidney.
"As a group, we think these bubbles, called acoustic cavitation, are important in stone breakage and kidney damage," said Dr. Evan. "This is a huge and exciting project which could ultimately eliminate much of the time-consuming portion of the research."
The Caltech team members will attempt to build a virtual lithotriptor to simulate what happens to the kidney in a shock wave path.
"There is a consistent theme to all of our research and that is to reduce the kidney's exposure to shock waves, improving the effectiveness of lithotripsy and safeguarding the patient's health," said Dr. Evan.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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