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

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: David G Warnock, Christie P Thomas, Bojan Vujkovac, Ruth C Campbell, Joel Charrow, Dawn A Laney, Leslie L Jackson, William R Wilcox, Christoph Wanner
• Journal: Journal of medical genetics (J Med Genet) Vol. 52 Issue 12 Pg. 860-6 (Dec 2015) ISSN: 1468-6244 [Electronic] England
• PMID: 26490103 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Isoenzymes
• alpha-Galactosidase
• agalsidase beta

Topics

• Adult
• Angiotensin Receptor Antagonists (adverse effects, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (adverse effects, therapeutic use)
• Drug Therapy, Combination
• Fabry Disease (complications, drug therapy)
• Female
• Glomerular Filtration Rate
• Humans
• Isoenzymes (adverse effects, therapeutic use)
• Kidney (drug effects, physiopathology)
• Kidney Diseases (drug therapy, etiology)
• Male
• Middle Aged
• Prospective Studies
• Treatment Outcome
• alpha-Galactosidase (adverse effects, therapeutic use)