Renal function predicts long-term outcome on enzyme replacement therapy in patients with Fabry disease.
BACKGROUND
Renal and cardiac involvement is responsible for substantial morbidity and mortality in Fabry disease (FD). We analysed the incidence of FD-related renal, cardiac and neurologic end points in patients with FD on long-term enzyme replacement therapy (ERT).


METHODS
A retrospective analysis of prospectively collected data from two German FD centres was performed. The impact of renal and cardiac function at ERT-naïve baseline on end point development despite ERT was analysed.


RESULTS
Fifty-four patients (28 females) receiving ERT (mean 81 ± 21 months) were investigated. Forty per cent of patients were diagnosed with clinical end points before ERT initiation and 50% of patients on ERT developed new clinical end points. In patients initially diagnosed with an end point before ERT initiation, the risk for an additional end point on ERT was increased {hazard ratio [HR] 3.83 [95% confidence interval (CI) 1.61-9.08]; P = 0.0023}. A decreased glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 in ERT-naïve patients at baseline was associated with an increased risk for cardiovascular end points [HR 3.59 (95% CI 1.15-11.18); P = 0.0273] as well as for combined renal, cardiac and neurologic end points on ERT [HR 4.77 (95% CI 1.93-11.81); P = 0.0007]. In patients with normal kidney function, left ventricular hypertrophy at baseline predicted a decreased end point-free survival [HR 6.90 (95% CI 2.04-23.27); P = 0.0018]. The risk to develop an end point was independent of sex.


CONCLUSIONS
In addition to age, even moderately impaired renal function determines FD progression on ERT. In patients with FD, renal and cardiac protection is warranted to prevent patients from deleterious manifestations of the disease.
Department ofNephrology, Hypertension, and Rheumatology, Internal Medicine D, University Hospital Muenster, Albert-Schweitzer-Campus 1, D-48149 Muenster, Germany.
Malte
M
Lenders
Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, University Hospital Muenster, Muenster, Germany.
Boris
B
Schmitz
Department of Cardiovascular Medicine, Division of Cardiology, University Hospital Muenster, Muenster, Germany.
Jörg
J
Stypmann
Department of Neurology, University Hospital Muenster, Muenster, Germany.
Thomas
T
Duning
Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, University Hospital Muenster, Muenster, Germany.
Stefan-Martin
SM
Brand
Department II ofInternal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Christine
C
Kurschat
Department ofNephrology, Hypertension, and Rheumatology, Internal Medicine D, University Hospital Muenster, Albert-Schweitzer-Campus 1, D-48149 Muenster, Germany.
Eva
E
Brand
D000328:Adult; D018450:Disease Progression; D056947:Enzyme Replacement Therapy / Q000009:adverse effects*; D000795:Fabry Disease / Q000150:complications* / Q000201:enzymology / Q000628:therapy; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies
Fabry disease; GFR; albuminuria; left ventricular hypertrophy; survival analysis