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Friday 26th May, 2006
MRI accurately tracks structural
changes that predict functional changes earlier than
standard blood and urine tests.
A new method using magnetic resonance imaging (MRI)
accurately tracks structural changes that predict functional
changes earlier than standard blood and urine tests in people
with autosomal dominant polycystic kidney disease (PKD),
according to a study funded by the National Institutes of Health
(NIH). PKD is a common inherited condition characterized by
cysts that grossly distort the kidneys and liver and by high
blood pressure and brain aneurysms (bulges in arteries).
Findings are in the May 18 issue of the New England Journal of
Researchers found that both small and large cysts and both
kidneys grew continuously at steady rates, seemingly tailored to
the individual with PKD, regardless of patient age. These
structural changes correlate with losses in kidney function,
suggesting that MRI can be used to track the major contributor
to the progression of PKD, an advance that could speed the
discovery of new therapies.
"There is so much variability in the loss of kidney function
among PKD patients, even within families with the same altered
gene, that it was assumed that cysts and kidneys must grow at
variable rates. So it's quite remarkable to find cysts and
kidneys in individuals growing at uniform and predictable
rates," said Catherine M. Meyers, M.D., a kidney specialist at
the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK). "Our experience is still limited, but this
method appears very promising."
The Consortium for Radiological Imaging Studies of Polycystic
Kidney Disease (CRISP) enrolled 241 patients, ages 15 to 46
years, with autosomal dominant PKD and normal to mild losses in
kidney function (stage 1 or 2). The researchers developed MRI
techniques to reliably and accurately produce 3-dimensional
images from which cysts and kidneys, and the proportion of the
kidneys occupied by cysts, could be measured. Changes in cyst
and kidney volume were compared to standard blood and urine
tests of kidney function and to a specialized test measuring how
fast the kidneys filtered a substance called iothalamate from
"Being able to predict how quickly a disease will
progress--rather than waiting years for it to actually
happen--should speed up trials of potential therapies. Up to now
we had to observe patients for years before we could tell if a
therapy was working," said lead author Jared J. Grantham, M.D.,
a kidney specialist at the University of Kansas School of
Medicine in Kansas City and long-time advocate for PKD patients.
"It should now be possible to test potential therapies earlier
in the disease, when therapies are more likely to prevent kidney
Already, the new MRI method is receiving closer scrutiny.
CRISP patients have been asked to stay for another 4 years of
MRI monitoring, and about 100 of them are planning to join
NIDDK's HALT-PKD trial (www.pkd.wustl.edu/pkd-tn), the first
intervention trial to use the MRI method along with standard
tests of kidney function. HALT-PKD enrolled its first patient in
January 2006 to learn if careful blood pressure control and
ACE-inhibitors or angiotensin receptor blockers (ARBs) can
prevent progression of PKD.
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CRISP clinical centers are at the University of Kansas Medical
Center in Kansas City, Emory University in Atlanta, Mayo Clinic
in Rochester, Minn., and the University of Alabama at
Birmingham. Washington University in St. Louis analyzed the MRI
images and study data.
As many as half a million people in the United States and 4
to 6 million world-wide are estimated to have PKD. In autosomal
dominant PKD, the most common form, symptoms usually appear
between the ages of 30 and 40 and include back and side pain and
headaches. Half of patients develop kidney failure, on average
around age 54; 23,000 were on dialysis or had a transplant for
kidney failure in 2003, making it this country's fourth leading
cause of kidney failure. More information about PKD is available
from NIDDK at www.niddk.nih.gov and from the PKD Foundation at
www.pkdcure.org and 1-800-PKD-CURE.
There is no cure and no specific treatment for PKD, but
careful blood pressure control and using ACE-inhibitors or ARBs,
types of blood pressure medicines, significantly delays or
prevents kidney disease and failure from diabetes and other
causes by reducing protein in the urine and preventing damage to
the small blood vessels in the kidneys. Earlier trials of these
treatments in PKD were not definitive, possibly because a small
number of patients were involved.