title: Kidney function and 24-hour proteinuria in patients with Fabry disease during 36 months of agalsidase alfa enzyme replacement therapy: a Brazilian experience.
abstract: BACKGROUND
  Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria.
  
  
  METHODS
  During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/ 1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >or= 90 mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73 m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73 m(2), and stage V as < 15 mL/min/1.73 m(2).
  
  
  RESULTS
  Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions administered.
  
  
  CONCLUSIONS
  Over the course of 36 months of ERT, there was no change in kidney function and 24-hour proteinuria. This suggests that agalsidase alfa may slow or halt the progression of kidney disease when used before extensive kidney damage occurs. No significant side effects were observed with ERT during the course of the study.
authors.affiliation: Post-Graduate Program of Medical Science, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. sthofehrn@terra.com.br
authors.forename: Scheila
authors.initials: S
authors.lastname: Thofehrn
authors.forename: Cristina
authors.initials: C
authors.lastname: Netto
authors.forename: Cláudia
authors.initials: C
authors.lastname: Cecchin
authors.forename: Maira
authors.initials: M
authors.lastname: Burin
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.forename: Sílvia
authors.initials: S
authors.lastname: Brustolin
authors.forename: Ane Cláudia Fernandes
authors.initials: AC
authors.lastname: Nunes
authors.forename: Janice
authors.initials: J
authors.lastname: Coelho
authors.forename: Marylin
authors.initials: M
authors.lastname: Tsao
authors.forename: Laura
authors.initials: L
authors.lastname: Jardim
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Elvino José Guardão
authors.initials: EJ
authors.lastname: Barros
mesh_terms: D000328:Adult; D001938:Brazil; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy / Q000503:physiopathology; D011994:Recombinant Proteins; D016896:Treatment Outcome; D055815:Young Adult; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase