The study, which will be published in the May 23 issue of the journal Science, is the first to suggest that proteins normally pass into the kidneys and that kidney disease may result from an inability to draw them back out. It also identifies at least two patients with kidney disease who lack one copy of CD2AP, suggesting that this mutation may be responsible for illness in some humans.
"Most experts believe that kidney disease is caused by an immune response against the kidney," explains principal investigator Andrey S. Shaw, M.D., professor of pathology and immunology at Washington University School of Medicine in St. Louis. "But our evidence suggests that defects that are intrinsic to the kidney also contribute to kidney failure."
Millions of people suffer from kidney disease and, according to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 65,000 Americans die of end-stage kidney failure every year. While several genes recently have been identified as potential factors, the mechanisms that contribute to disease development are poorly understood.
In 1999, Shaw's team discovered that mice completely lacking CD2AP quickly develop kidney disease and die from kidney failure after about six weeks. The results suggest that this protein is critical for the kidneys to function, but the researchers recognized that very few humans are likely to be missing both copies of this gene. So they examined the effects of missing only one copy.
After about nine months, mice with only one copy of CD2AP appeared healthy but, when examined after death, they had abnormalities in their glomerul
Contact: Gila Z. Reckess
Washington University School of Medicine