Health
Studies to test best ways to check PKD
■ Polycystic kidney disease, though a common condition, is often not diagnosed and treated until much damage has been done.
By Susan J. Landers — Posted March 6, 2006
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Washington -- Two large treatment trials have been launched for polycystic kidney disease, a common inherited disorder that often leads to kidney failure. About half of the 500,000 Americans with the disease eventually will undergo dialysis or a kidney transplant.
Over the next two years, 1,000 patients with the most common form of the disease, autosomal dominant polycystic kidney disease, will be enrolled in the trials and treated for up to four years at centers in Atlanta; Boston; Cleveland; Denver; Kansas City, Kan.; and Rochester, Minn.
The disease affects not only the kidneys, in which numerous cysts can slowly replace much of the mass of the kidneys, but also the liver, brain and heart, increasing the risk of early death. Earlier diagnosis and treatment are thought to be key to avoiding the most serious outcomes.
"We have good reason to believe that if you find the disease early enough in life and treat it early enough, you can shut the door before the horse even gets out of the barn," said Daniel Larson, the CEO of the PKD Foundation, which is sponsoring the trials with the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases.
But identifying the disease early can be problematic. "We find that a lot of physicians in general aren't familiar with the disorder," said Ronald Perrone, MD, vice chair of the PKD Foundation's Scientific Advisory Committee and associate chief at Tufts-New England Medical Center's Division of Nephrology.
Warning signs
Awareness of a family history of PKD should raise a red flag, Dr. Perrone said. Autosomal dominant PKD is one of the most common inherited disorders. If one parent has the disease, there is a 50% chance that the disease will pass to the child.
Chronic hypertension for no apparent reason is another common marker for the disease, Larson said, as is chronic back pain, blood in the urine or recurring kidney infections.
The randomized controlled trials will build on earlier findings showing that by carefully controlling blood pressure, the disease could be held in check. Researchers in the HALT-PKD study will compare conventional hypertension therapy using an ACE inhibitor to more intensive blockade of the renin-angiotensin system using an ACE inhibitor and an angiotensin receptor blocker.
Study A is enrolling people ages 15 to 49 with early disease and will compare standard -- 120-130/70-80 mm Hg -- and low -- 95-110/60-75 mm Hg -- blood pressure targets and measure changes in cyst and kidney size using magnetic resonance imaging.
"The novel thing about this trial is that it is going to use kidney growth as assessed by MRI as an outcome measure," Dr. Perrone said.
Earlier clinical trials studied kidney function and were likely looking at the late stages of the disease when interventions were likely to be less helpful, or they were looking at early stages of the disease where change in kidney function was slow, he noted.
A second trial, for people ages 18 to 64 with more advanced kidney disease, will track the time it takes a standard kidney function measurement -- the estimated glomerular filtration rate, or eGFR -- to drop by 50%, the need for kidney failure treatment and patient deaths.
The disease is diagnosed by sonogram to assess whether there are cysts in the kidneys. "If by age 30 the sonogram is negative, then you are 99% in the clear," Larson said. "Unfortunately, by the time you are in your 30s, there has likely been damage to the kidneys."
Encouraging people to be diagnosed is difficult because they fear genetic discrimination. "If you're 20 years old and are diagnosed by ultrasound with PKD, by definition you have a preexisting condition," Dr. Perrone said. "So many people avoid getting tested and, as a result, don't have access to treatment. So it's a double-edged sword."