Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation

Abstract

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/1.73m(2)/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m(2)/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/1.73m(2)/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.

Fig. 1.

Patients with rapid renal disease progression experienced clinical events prior to the initiation of agalsidase beta treatment. Patients were grouped into quartiles (Q), based on eGFR slope. Data are expressed as the percentage of patients within each eGFR slope quartile who had a stroke or cardiovascular event (as defined in Materials and Methods section) prior to the initiation of agalsidase beta treatment. The numbers above each bar indicate number of patients who had clinical events prior to the initiation of treatment/total number of patients in each quartile. Data for males are shown in light grey bars and data for females are shown in dark grey bars.