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News from ScienceDaily.com July 27,
2007
Combination Therapy Stops Loss Of
Kidney Function In Rare Genetic Disease
Science Daily — A combination of two types of blood
pressure-lowering drugs--an angiotensin-converting enzyme inhibitor
(ACEI) plus an angiotensin-receptor blocker (ARB), added to enzyme
replacement therapy (ERT) with agalsidase-beta (Fabrazyme®, Genzyme
Corporation, Cambridge, MA)--is the first treatment shown to stop
progressive loss of kidney function in patients with severe kidney
involvement due to the rare genetic disorder Fabry disease, reports
a study in the September Journal of the American Society of
Nephrology.
"While Fabry disease is very rare, our study shows that controlling
urine protein excretion will slow progression of kidney disease,
even though the achieved blood pressures were lower than are usually
targeted in treating chronic kidney disease," says Dr. David Warnock
of University of Alabama, Birmingham, one of the study authors.
Dr. Warnock and colleagues report encouraging results with ACEI/ARB
therapy in eleven patients with progressive loss of kidney function
related to Fabry disease (Fabry nephropathy). Fabry disease is a
rare genetic disorder caused by problems with an enzyme called
alpha-galactosidase-A, which the body needs to metabolize lipids (fatty
substances). Even with treatment to replace the missing enzyme,
buildup of lipids can cause progressive kidney, brain, and heart
disease. In the current study, four patients had relatively mild
kidney disease (stage 1 to 2), while seven had more severe loss of
kidney function (stage 3 to 4).
All patients received ERT and combined ACEI/ARB treatment. The ACEIs
and ARBs are widely used in patients with chronic kidney disease and
proteinuria--"leakage" of protein into the urine associated with
progressive loss of kidney function. Treatment is usually based on
the patient's blood pressure. However, the situation is different in
patients with Fabry disease, who often have low to normal blood
pressure despite kidney disease.
The ACEI/ARB combination effectively controlled the patients' level
of proteinuria. Among six patients with severe kidney disease,
treatment greatly slowed the rate of deterioration in kidney
function and reduced urine protein loss--in contrast, previous
studies have reported no beneficial effect of ERT alone on
proteinuria. After an average of two and a half years' treatment,
the UAB patients had only a minimal decline in kidney function,
which was not significantly from zero.
The combination of ERT and ACEI/ARB therapy also stabilized kidney
function in patients with less severe kidney disease and milder
degrees of proteinuria. Aside from some minor problems related to
episodes of low blood pressure, there were no serious side effects
of ACEI/ARB treatment.
Studies in other groups of patients with chronic kidney disease have
highlighted the importance of treatment with an ACEI and/or ARB to
control proteinuria. Although most of the improvement probably
results from reductions in blood pressure, other effects may
contribute as well. In patients with Fabry disease, ERT is of some
help in treating mild kidney disease, but is less effective in those
with more severe kidney disease and proteinuria.
"This work shows for the first time that it is possible to stop
progressive decline of kidney function in patients who have Fabry
disease with advanced kidney involvement and proteinuria," Dr.
Warnock concludes. "The results were everything we hoped for, and
are now being confirmed in a sixteen-site international multicenter
trial."
Dr Warnock is a consultant for Genzyme Corporation and has received
research support from Genzyme Corporation. The study referenced
above was not supported by the Genzyme Corporation.
The study entitled, "Anti-Proteinuric Therapy and Fabry Nephropathy:
Sustained Reduction of Proteinuria in Patients Receiving Enzyme
Replacement Therapy with Agalsidase-Beta" will be available online
beginning on Wednesday, July 25 and in print in the September issue
of the Journal of the American Society of Nephrology.
Note: This story has been adapted from a news release issued by
American Society of Nephrology.
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http://www.sciencedaily.com/releases/2007/07/070726085928.htm
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