New Clues to Genes Tied to Polycystic Kidney Disease

Absence of a gene linked to a potentially fatal kidney disease causes the kidney, pancreas and heart to develop abnormally, Yale researchers say.

The significance of these findings, as well as related discoveries in the same report, said Stefan Somlo, M.D., of the Yale School of Medicine, is that researchers now have more essential information about a gene known to be critical in development of polycystic kidney disease (PKD). The study was published this month in Nature Genetics.

PKD is the most common, life-threatening genetic disease in the United States, affecting some 600,000 Americans. There is currently no known treatment or cure for the disease, which results in about 1,000 deaths each year due to kidney failure.

Yale last fall received a $5.6 million grant from the National Institutes of Health to establish a center of excellence for the study of PKD. The five-year grant was the largest of those awarded to four such research centers nationwide.

“We have two genes, PKD1 and PKD2, which were completely novel when discovered and which, when mutated, cause polycystic kidney disease,” said Somlo, associate professor of internal medicine (nephrology) and genetics. “We need to determine what the genes do normally, understand what happens when they are defective, and, finally, find an avenue to treat or perhaps even cure PKD.”

Three significant findings are contained in the Nature Genetics report. First, in the absence of the PKD2 gene, the heart as well as the kidneys and pancreas do not develop normally. Second, when only one, instead of two, normal copies of the PKD2 gene is present in the mice being tested, the mice die more quickly, but not from kidney failure. However, when individual mice have a mixture of either one or no normal copies of the gene, they develop cysts and kidney failure just like the human disease.

The Yale PKD research center, headed by Somlo, the principal author of the report, is a multi-disciplinary group including investigators from the departments of cellular and molecular physiology, pharmacology, pathology and genetics, as well as internal medicine/nephrology.

The study reported in Nature Genetics also involved researchers from Albert Einstein College of Medicine and Columbia University.

Although about 600,000 Americans have PKD, it is estimated that only about 100,000 people are aware they have the condition. Symptoms include high blood pressure, constant or intermittent pain in the back, side or stomach, blood in urine, kidney stones, frequent urinary tract infections, and a family history of kidney problems.

In PKD, water balloon-type cysts develop in the kidneys and cause the kidneys to enlarge while interfering with normal functioning. By middle age, many people with PKD need dialysis or transplantation. The children of an adult with PKD have a 50 percent chance of inheriting the disease.

Share this with Facebook Share this with Twitter Share this with LinkedIn Share this with Email Print this