Combination Therapy Benefits Fabry Disease Patients

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Combining an ACE inhibitor (ACEI) and angiotensin-receptor blocker (ARB) with enzyme replacement therapy using agalsidase-beta (Fabrazyme, Genzyme) may help stop progressive loss of kidney function in patients with severe kidney involvement due to Fabry disease, researchers report.

"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," said David Warnock, MD, of the University of Alabama in Birmingham, one of the investigators.

Dr. Warnock and his colleagues studied the new treatment approach in 11 patients with progressive loss of kidney function as a result of Fabry disease, a rare genetic disorder that results from a deficiency of alpha-galactosidase-A, an enzyme involved in lipid metabolism.

The condition can lead to buildup of lipids that can cause progressive kidney, brain, and heart disease. In the new study, four patients had relatively mild chronic kidney disease (CKD stage 1 to 2) and seven had more severe loss of kidney function (CKD stage 3 to 4).

All patients received enzyme replacement therapy and combined ACEI/ARB treatment. The ACEI/ARB combination effectively controlled patients' proteinuria. In six patients with severe CKD, the treatment slowed the rate of deterioration in kidney function and reduced urine protein loss. Previous studies have found no beneficial effect of ERT alone in controlling proteinuria.

After an average of 2.5 years of treatment, the patients had only a minimal decline in kidney function. Findings were published recently in the online version of the Journal of the American Society of Nephrology. The study is scheduled to be published in the print version this September.

The combination of ERT and ACEI/ARB therapy also stabilized kidney function in patients with less severe CKD and milder degrees of proteinuria. The researchers observed no serious adverse effects.

"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 CKD."

A major implication of this study is that ACEI/ARB therapy could be used in patients with more common forms of CKD and proteinuria to reduce the proteinuria to less than  500 mg/day, rather than targeting a fixed blood pressure goal in guiding and titrating the ACEI/ARB therapy.

Dr. Warnock is a consultant for Genzyme and has received research support from the company. The new study, however, was not sponsored by Genzyme.

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