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

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


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cardiovascular Diseases / complications
  • Comorbidity
  • Disease Progression
  • Enzyme Replacement Therapy / adverse effects*
  • Fabry Disease / complications
  • Fabry Disease / drug therapy*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenotype
  • Prognosis
  • Proportional Hazards Models
  • Proteinuria / complications
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome
  • Triglycerides / blood
  • Young Adult


  • Triglycerides

Grant support

This study was supported by a grant (project number: 836011009) from the Ministry of Health (ZonMw) of the Netherlands. Researchers worked independently from the funders. The funding source had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit an article for publication. The collection of data at University Hospital Wuerzburg has been supported by the Bundesministerium für Bildung und Forschung of the Federal Republic of Germany (BMBF 01EO1504 MO2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.