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Author Notes:

Correspondence to Dr David G Warnock, Room 614 ZRB, UAB, 1720 2nd Avenue South, Birmingham, AL 34294-0007, USA; dwarnock@uab.edu

All of the authors were involved in the initial concept of the manuscript and have reviewed and commented on all drafts and data. DGW had full access to the data, performed the statistical analyses, wrote the initial draft and had final responsibility for the decision to submit for publication.

Collaborators: FAACET Investigators.

The authors thank the patients and investigators who participated in the FAACET study.

Competing interests: Members of the Fabry Registry Board of Advisors (receiving expense reimbursement from Genzyme) include DGW, BV, JC, DAL, WRW and CW. The authors who have received research funds, travel support or speaking fees from Genzyme include DGW, BV, JC, DAL, WRW and CW. DGW has received consulting fees from Genzyme, Shire HGT and Amicus Therapeutics. JC has received consulting fees from Shire HGT, BioMarin and Protalix Corporation. WRW has served as a paid consultant to Amicus Therapeutics and Shire HGT.


Research Funding:

Genzyme, a Sanofi company, the FAACET Study, as an investigator Sponsored Study to the University of Alabama at Birmingham (DGW, principal investigator). Genzyme also funds the Fabry Registry.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • 10-YEAR

Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy


Journal Title:

Journal of Medical Genetics


Volume 52, Number 12


, Pages 860-U91

Type of Work:

Article | Final Publisher PDF


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.

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This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

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