RT Journal Article
SR Electronic
T1 Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 860
OP 866
DO 10.1136/jmedgenet-2015-103471
VO 52
IS 12
A1 David G Warnock
A1 Christie P Thomas
A1 Bojan Vujkovac
A1 Ruth C Campbell
A1 Joel Charrow
A1 Dawn A Laney
A1 Leslie L Jackson
A1 William R Wilcox
A1 Christoph Wanner
YR 2015
UL http://jmg.bmj.com/content/52/12/860.abstract
AB 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.Trial registration number NCT00446862.