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 1*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.
Bibliographical noteFunding Information:
1University of Alabama at Birmingham, Birmingham, AL, USA, 2IIS-Fundación Jiménez Díaz and Universidad Autonoma de Madrid, Madrid, Spain, 3University of Minnesota, Minneapolis, MN, USA, 4Academic Medical Center, Amsterdam, Netherlands, 5Hospital São João, Faculty of Medicine, Porto, Portugal, 6University of Zurich, Zurich, Switzerland, 7University of Debrecen Medical and Health Science Center, Debrecen, Hungary, 8Department of Nephrology and Dialysis, Infermi Hospital, Rimini, Italy, 9General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia, 10Genzyme Corporation, Cambridge, MA, USA, 11Department of Medicine, Haukeland University Hospital, and Institute of Medicine, University of Bergen, Bergen, Norway, 12Salford Royal NHS Foundation Trust, Manchester, UK, 13Hôpital Raymond Poincaré (AP-HP), University of Versailles, Garches, France and 14University of Würzburg, Würzburg, Germany
- Alpha galactosidase
- Enzyme replacement therapy
- Fabry disease
- Genetic renal disease