Journal article
Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy
Journal of medical genetics, Vol.52(12), pp.860-866
12/2015
DOI: 10.1136/jmedgenet-2015-103471
PMCID: PMC4717450
PMID: 26490103
Abstract
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.
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.
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 m(2)/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 m(2)/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.
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.
NCT00446862.
Details
- Title: Subtitle
- Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy
- Creators
- David G Warnock - Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USAChristie P Thomas - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USABojan Vujkovac - General Hospital, Slovenj Gradec, SloveniaRuth C Campbell - Department of Medicine, Medical University of South Caroline, Charleston, South Carolina, USAJoel Charrow - Departments of Pediatrics-Genetics, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USADawn A Laney - Department of Human Genetics, Emory University, Atlanta, Georgia, USALeslie L Jackson - Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USAWilliam R Wilcox - Department of Human Genetics, Emory University, Atlanta, Georgia, USAChristoph Wanner - Department of Nephrology, University Klinik Würzburg, Würzburg, Germany
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.52(12), pp.860-866
- DOI
- 10.1136/jmedgenet-2015-103471
- PMID
- 26490103
- PMCID
- PMC4717450
- NLM abbreviation
- J Med Genet
- ISSN
- 1468-6244
- eISSN
- 1468-6244
- Publisher
- England
- Language
- English
- Date published
- 12/2015
- Academic Unit
- Stead Family Department of Pediatrics; Obstetrics and Gynecology; Internal Medicine
- Record Identifier
- 9983985905202771
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