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

• Authors: David G Warnock, University of Alabama at Birmingham; Christie P Thomas, University of Iow; Bojan Vujkovac, General Hospital, Slovenj Gradec; Ruth C Campbell, Medical University of South Carolina; Joel Charrow, Northwestern University; Dawn Laney, Emory University; Leslie L Jackson, University of Alabama at Birmingham; William Wilcox, Emory University; Christoph Wanner, University Klinik Würzburg
• Journal Title: Journal of Medical Genetics
• Volume: Volume 52, Number 12
• Publisher: BMJ Publishing Group | 2015-12-01, Pages 860-U91
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1136/jmedgenet-2015-103471
• Subjects: Health Sciences, Medicine and Surgery; Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Genetics & Heredity; ENZYME-REPLACEMENT THERAPY; GLOMERULAR-FILTRATION-RATE; DISEASE PROGRESSION; ALPHA-GALACTOSIDASE; RENAL-DISEASE; REGISTRY; FEMALES; PROTEINURIA; INVOLVEMENT; 10-YEAR

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 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.