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PLoS One. 2017 Aug 1;12(8):e0182379. doi: 10.1371/journal.pone.0182379. eCollection 2017.

Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry disease: Analysis of prognostic factors.

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Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
Department of Haematology, Royal Free London NHS Foundation Trust and University College London, London, United Kingdom.
Department of Cardiology, St Bartholomew's Hospital and University College London, London, United Kingdom.
Department of Internal Medicine I, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center (CHFC) and Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Wuerzburg, Wuerzburg, Germany.
Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands.


Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension.

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