After six months of painstaking detective work, Johns Hopkins researchers have decoded the molecules that make up the complex gene that causes polycystic kidney disease, the most common inherited disease in the United States.
While European scientists had partially identified the gene last year, the Hopkins team finished that work and created a "blueprint" for understanding the biology and evolution of the gene. That means researchers will now be able to figure out how the gene functions -- and why it mutates.
"It's a little bit of 'eureka,' " said Dr. Gregory G. Germino, Hopkins' principal investigator on the project.
The Hopkins researchers are part of a consortium that includes the biotechnology company Integrated Genetics and the Los Alamos National Laboratory. They will present their findings today at a conference sponsored by the National Institute for Diabetes, Digestive and Kidney Diseases in Bethesda.
For patients, the work has a practical implication -- it brings researchers a step closer to finding a way to treat the disease or even cure it. Now, all physicians can do is treat complications such as kidney stones, high blood pressure and kidney infections.
More than 500,000 Americans have the disease, known as PKD, and half of these patients will eventually have kidney failure. PKD is passed from parent to child in the form of a defective gene. Because of the mistake in the gene, cells pump too much fluid into tubes only a hair's breadth wide.
Slowly, over many years, so much fluid is pumped in that some tubes develop into cysts. Even though there are more than 1 million filtering tubes in the kidney and only 1 percent ever become cysts, the cysts can grow to the size of oranges. They crowd out and destroy normal tissue.
But because the cysts grow at such a slow rate, the patient doesn't experience symptoms until middle age, when blood in the urine or abdominal pain signal a problem. Roughly 40 percent of the people with the disease don't know they have it, Dr. Germino said.
Eventually, half of these patients will need a transplant or dialysis.
And though not as widely known as other, less common diseases such as cystic fibrosis, PKD racks up a $1 billion bill nationwide each year.
"It's a common disease. There's a lot of people at risk," said Dr. Germino. "There's a lot of people who suffer a lot."
Dr. Gary Striker, a scientist from the National Institute for Diabetes, Digestive and Kidney Diseases who is overseeing today's conference, said the Hopkins work is essential to the next step in PKD research: figuring out what specific mechanism is making the cells pump too much fluid. He predicts that within five years, scientists will have the answer.
"It's obviously terribly exciting anytime something is mapped for polycystic kidney disease," said Dr. Garabed Eknoyan, vice president of the National Kidney Foundation. "It's a breakthrough."
Meanwhile, patients who won't be able to take advantage of future therapies are on dialysis or waiting for a transplant.
Charles Holly was 48 years old when he was in the hospital for a hernia operation and physicians discovered he had PKD. Since then, he has experienced little pain or any symptoms.
But now, at age 65, the cysts have started to affect the Alexandria, Va., man's kidney function. The organs aren't filtering blood like they should. Each time he goes to the doctor, more and more waste products are in his blood. He must stick to a restrictive diet, including only 3 ounces of protein a day and a thimbleful of apple juice.
Mr. Holly's father died from the disease. His sister and daughter have it. Two of his sons don't want to be tested, fearing they'll lose their health insurance if it is discovered that they have the disease.
Mr. Holly's other child, a son named John, has decided he wants to donate one of his kidneys to his father. Tests have shown that he is a perfect match.
But the family is now waiting for one more test: to see if John, 38, has PKD, too -- or if he is healthy and can donate the kidney.
For more information on polycystic kidney disease, call the Polycystic Kidney Research Foundation at 1-800-PKD-CURE.