title: Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation.
abstract: BACKGROUND
  The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta.
  
  
  METHODS
  Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression.
  
  
  RESULTS
  Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m(2)/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m(2)/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4-3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2-184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m(2)/year).
  
  
  CONCLUSIONS
  Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA. dwarnock@uab.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
authors.forename: Gabor E
authors.initials: GE
authors.lastname: Linthorst
authors.forename: João P
authors.initials: JP
authors.lastname: Oliveira
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Serra
authors.forename: László
authors.initials: L
authors.lastname: Maródi
authors.forename: Renzo
authors.initials: R
authors.lastname: Mignani
authors.forename: Bojan
authors.initials: B
authors.lastname: Vujkovac
authors.forename: Dana
authors.initials: D
authors.lastname: Beitner-Johnson
authors.forename: Roberta
authors.initials: R
authors.lastname: Lemay
authors.forename: J Alexander
authors.initials: JA
authors.lastname: Cole
authors.forename: Einar
authors.initials: E
authors.lastname: Svarstad
authors.forename: Stephen
authors.initials: S
authors.lastname: Waldek
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Germain
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
mesh_terms: D000328:Adult; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications* / Q000628:therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000209:etiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology*; D013997:Time Factors; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D003404:Creatinine; D000519:alpha-Galactosidase; C459420:agalsidase beta