Wirkung der Enzymersatztherapie (ERT) auf die Nierenfunktion von Patienten mit Morbus Fabry

Abstract

Fabry's disease is an inherited lysosomal storage disorder characterized by the lack of enzyme alpha-galactosidase A (alpha-Gal A) which degrades globotriaosylceramides (Gb3) into products with lower molecular weight. The accumulation of Gb3 in different cell types is responsible for the variety of clinical manifestations. The renal function, estimated via proteinuria, hematuria and reduction of glomerular filtration rate (GRF), is heavily affected. Currently, substitution of alpha-Gal A remains the only therapeutic option for patients with Fabry's disease. Two products are approved for the treatment of Fabry's disease: agalsidase alfa and agalsidase beta. Both of these enzymes have shown a stabilization of renal function in various studies when evaluated by the creatinine clearance, estimated GFR, and serum creatinine. The pro gnosis has proven to be significantly better in cases of mild or moderate renal insufficiency from the baseline. For this reason, an early substitution of the lacking enzyme is necessary. Furthermore, enzyme replacement therapy (ERT) has proven efficient in reducing the amount of intracellular Gb3 and Gb3 in urine. Without treatment, an eGFR reduction of approximately 12 ml/min/year has been reported. After diverse studies of ERT, no significant correlation between enzyme substitution and improvement of patients' proteinuria could be shown. Furthermore, renoprotective drugs have not been consistently applied so far in the ERT trials. In any case, further studies to evaluate the long-term effect of ERT on the morbidity and mortality of patients with Fabry's disease are necessary.

Erythematöse Papeln bei einem 26-jährigen Patienten

“…Mit der Enzymersatztherapie [Agalsidase alfa (Replagal®) und Agalsidase beta (Fabrazyme®)] steht eine gut wirksame Therapie zur Verfügung. Die Behandlung erfolgt lebenslang in 14-tägigen Abstän-den und kann bei guter Verträglichkeit nach einigen Monaten auch als Heiminfusionstherapie durchgeführt werden [6].…”