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Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy
  1. David G Warnock1,
  2. Christie P Thomas2,
  3. Bojan Vujkovac3,
  4. Ruth C Campbell4,
  5. Joel Charrow5,
  6. Dawn A Laney6,
  7. Leslie L Jackson1,
  8. William R Wilcox6,
  9. Christoph Wanner7
  1. 1Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  2. 2Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
  3. 3General Hospital, Slovenj Gradec, Slovenia
  4. 4Department of Medicine, Medical University of South Caroline, Charleston, South Carolina, USA
  5. 5Departments of Pediatrics-Genetics, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
  6. 6Department of Human Genetics, Emory University, Atlanta, Georgia, USA
  7. 7Department of Nephrology, University Klinik Würzburg, Würzburg, Germany
  1. Correspondence to Dr David G Warnock, Room 614 ZRB, UAB, 1720 2nd Avenue South, Birmingham, AL 34294-0007, USA; dwarnock{at}


Background Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy.

Methods and design The goal was maintenance of urine protein to creatinine ratio (UPCR) <0.5 g/g or a 50% reduction in baseline UPCR for 24 patients at eight study sites. The change in estimated glomerular filtration rate (eGFR) was assessed over 21 months of treatment.

Results 18 out of 24 patients achieved the UPCR goal with eGFR slopes that were significantly better than six patients who did not achieve the UPCR goal (−3.6 (−4.8 to −1.1) versus −7.0 (−9.0 to −5.6) mL/min/1.73 m2/year, respectively, p=0.018). Despite achieving the UPCR goal, 67% (12/18 patients) still progressed with an eGFR slope <−2 mL/min/1.73 m2/year. Regression analysis showed that increased age at initiation of agalsidase-beta therapy was significantly associated with worsened kidney outcome. Hypotension and hyperkalaemia occurred in seven and eight patients, respectively, which required modification of antiproteinuric therapy but was not associated with serious adverse events.

Conclusions This study documents the effectiveness of agalsidase-beta (1 mg/kg/2 weeks) and antiproteinuric therapy with ACE inhibitors and/or ARB in patients with severe Fabry nephropathy. Patients had preservation of kidney function if agalsidase-beta treatment was initiated at a younger age, and UPCR maintained at or below 0.5 g/g with antiproteinuric therapy.

Trial registration number NCT00446862.

  • Renal Medicine
  • Metabolic disorders
  • Clinical genetics

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