TY  - JOUR
A1  - Warnock, David G.
A1  - Ortiz, Alberto
A1  - Mauer, Michael
A1  - Linthorst, Gabor E.
A1  - Oliveira, João P.
A1  - Serra, Andreas L.
A1  - Maródi, László
A1  - Mignani, Renzo
A1  - Vujkovac, Bojan
A1  - Beitner-Johnson, Dana
A1  - Lemay, Roberta
A1  - Cole, J. Alexander
A1  - Svarstad, Einar
A1  - Waldek, Stephen
A1  - Germain, Dominique P.
A1  - Wanner, Christoph
T1  - Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation
JF  - Nephrology Dialysis Transplantation
N2  - 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/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of –6.7 mL/min/1.73m2/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/1.73m2/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.
KW  - proteinuria
KW  - enzyme replacement therapy
KW  - alpha galactosidase
KW  - Fabry disease
KW  - genetic renal disease
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124697
VL  - 27
IS  - 3
ER  - 
TY  - THES
A1  - Henckel, Kay Yasmin
T1  - Klinische Verträglichkeit der Langzeit-Enzymersatztherapie mit rekombinanter α- und β-Agalsidase bei Patienten mit Morbus Fabry
T1  - Clinical tolerance of long-term enzyme replacement therapy with recombinant α- and β-Agalsidase in patients with Morbus Fabry
N2  - Morbus Fabry ist eine X-chromosomal vererbte, lysosomale Speicherkrankheit, die durch einen Mangel an α-Galaktosidase A hervorgerufen wird. Der Enzymdefekt führt zu einer progressiven intrazellulären Akkumulation von Glykosphingolipiden, die sich epithelial, glomerulär und interstitiell ablagern. Dadurch kommt es frühzeitig zu Organschäden wie Niereninsuffizienz, Myokardinfarkt und zerebralem Insult. Seit 2001 ist eine exogene Substitution mit humaner, rekombinant hergestellter α-Galaktosidase A (Replagal® und Fabrazyme®) verfügbar. Die vorliegende Dissertation erfasst objektiv, systematisch und standardisiert das in der Praxis relevante Auftreten von unerwünschten Nebenwirkungen unter der Enzymersatztherapie. Zusätzlich werden anhand von Geschlecht, Prämedikation, Lebensalter, Therapie- und Infusionsdauer beide Präparate auf ihre Verträglichkeit miteinander verglichen und ihr Einfluss auf unerwünschte Arzneimittelwirkungen untersucht.
N2  - The dissertation is about the tolerance of long-term enzyme replacement therapy in patients with Morbus Fabry. Also the influence of sex, premedication, age and duration of infusion on the tolerace of replacement therapy was determined.
KW  - α- und β-Agalsidase
KW  - Enzymersatztherapie
KW  - Verträglichkeit der Enzymersatztherapie
KW  - Morbus Fabry
KW  - Morbus Fabry
KW  - enzyme replacement therapy
KW  - α-Agalsidase
KW  - β-Agalsidase
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74706
ER  -