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Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy.
J Med Genet. 2015 Dec; 52(12):860-6.JM

Abstract

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 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.

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.

Authors+Show Affiliations

Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.General Hospital, Slovenj Gradec, Slovenia.Department of Medicine, Medical University of South Caroline, Charleston, South Carolina, USA.Departments of Pediatrics-Genetics, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.Department of Human Genetics, Emory University, Atlanta, Georgia, USA.Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.Department of Human Genetics, Emory University, Atlanta, Georgia, USA.Department of Nephrology, University Klinik Würzburg, Würzburg, Germany.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26490103

Citation

Warnock, David G., et al. "Antiproteinuric Therapy and Fabry Nephropathy: Factors Associated With Preserved Kidney Function During Agalsidase-beta Therapy." Journal of Medical Genetics, vol. 52, no. 12, 2015, pp. 860-6.
Warnock DG, Thomas CP, Vujkovac B, et al. Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy. J Med Genet. 2015;52(12):860-6.
Warnock, D. G., Thomas, C. P., Vujkovac, B., Campbell, R. C., Charrow, J., Laney, D. A., Jackson, L. L., Wilcox, W. R., & Wanner, C. (2015). Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy. Journal of Medical Genetics, 52(12), 860-6. https://doi.org/10.1136/jmedgenet-2015-103471
Warnock DG, et al. Antiproteinuric Therapy and Fabry Nephropathy: Factors Associated With Preserved Kidney Function During Agalsidase-beta Therapy. J Med Genet. 2015;52(12):860-6. PubMed PMID: 26490103.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy. AU - Warnock,David G, AU - Thomas,Christie P, AU - Vujkovac,Bojan, AU - Campbell,Ruth C, AU - Charrow,Joel, AU - Laney,Dawn A, AU - Jackson,Leslie L, AU - Wilcox,William R, AU - Wanner,Christoph, Y1 - 2015/10/21/ PY - 2015/08/22/received PY - 2015/09/25/accepted PY - 2015/10/23/entrez PY - 2015/10/23/pubmed PY - 2016/9/13/medline KW - Clinical genetics KW - Metabolic disorders KW - Renal Medicine SP - 860 EP - 6 JF - Journal of medical genetics JO - J Med Genet VL - 52 IS - 12 N2 - 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 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. 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. SN - 1468-6244 UR - https://www.unboundmedicine.com/medline/citation/26490103/Antiproteinuric_therapy_and_Fabry_nephropathy:_factors_associated_with_preserved_kidney_function_during_agalsidase_beta_therapy_ L2 - https://jmg.bmj.com/lookup/pmidlookup?view=long&amp;pmid=26490103 DB - PRIME DP - Unbound Medicine ER -