Current theory on cause of kidney stones refuted

New research into the origin of kidney stone formation published in the March 1 issue of the Journal of Clinical Investigation may well change the direction of the most basic level of research in that area.

The study, conducted at Indiana University School of Medicine, Clarian Health Partners and the University of Chicago, will dispel the current beliefs of where stone formation begins, said Andrew P. Evan, Ph.D., the article’s lead author. Dr. Evan, who is a professor of anatomy and cell biology at IU School of Medicine, said the research did confirm a hypothesis published in 1940 by Alexander Randall, M.D.

Dr. Randall theorized that kidney stones developed from crystals of calcium phosphate in a centrally located area of the kidney known as the papilla tip. However, analytical and imaging tools available during Dr. Randall’s day were inadequate to confirm his hypothesis. Today, the primary theory is that cell injury is necessary before crystals can attach to kidney tissue and develop and that crystals are composed of calcium oxalate. Both theories were refuted by the current Clinical Investigation article.

“Our research localized the site of the original mineral deposit for the most common group of stone formers and we have determined the composition of the crystal,” Dr. Evan said. That composition is calcium phosphate, a common component of bone and teeth. Dr. Randall surmised that calcium phosphate was the primary component of stones in their formation phase even though kidney stones later in the process are composed almost entirely of calcium oxalate.

Using infrared analysis, researchers looked at tissue from three groups of kidney patients: calcium oxalate stone formers, who account for 75 percent of all kidney stone patients; patients prone to developing kidney stones following intestinal bypass surgery for obesity; and a control group of patients who had malignant tumors in their ureters, a tube that carries urine to the bladder.

Kidney biopsies of the living patients pinpointed the initial sites where the changes begin and the stones form, said Dr. Evan. “This phase of the research was made possible by advances in equipment and surgical protocol not available in Randall’s day,” Dr. Evan said. “They represent the state-of-the-art approach for kidney stone treatment.”

Researchers learned that in the first group, the calcium phosphate crystals are first deposited in the interstitial tissue inside the papilla, as surmised by Dr. Randall. However, in the obesity-related bypass group, the crystals begin in the lining of very small tubules as they thread their way to the ureter. The control group showed no sign of stone formation.

Dr. Evan said ongoing research for a third group of stone formers, not included in this report, indicates yet a third location as the initial site for crystals.

“There are unique features about the physiology and diet specific to the various kinds of stone formers,” Dr. Evans says. “However, our research is the first evidence to give investigators a place to begin the search.”

Dr. Evan was joined in the research by James E. Lingeman, M.D., from the Methodist Hospital (Indianapolis) Institute for Kidney Stone Disease, and Fredric L. Coe, M.D., professor of medicine and physiology in the Section of Nephrology at the University of Chicago.

Funding for study was provided by a $5.6 million, five-year grant from the National Institutes of Health.

Kidney stones can take up to 10 years to form and affect up to 5 percent of the U.S. population. In 1993, the most recent year with available figures, total cost of the condition to patients in the United States was more than $1.8 billion.