ORCID Profile
0000-0003-4897-1378
Current Organisation
Dalhousie University
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Publisher: Informa UK Limited
Date: 10-2019
DOI: 10.2147/DDDT.S207856
Publisher: Elsevier BV
Date: 11-2010
Publisher: MDPI AG
Date: 17-08-2022
DOI: 10.3390/JCM11164810
Abstract: Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, without treatment, can cause significant renal dysfunction. We evaluated the effects of enzyme replacement therapy with agalsidase alfa on renal decline in patients with Fabry disease using data from the Fabry Outcome Survey (FOS) registry. Male patients with Fabry disease aged years at agalsidase alfa start were stratified by low (≤0.5 g/24 h) or high ( .5 g/24 h) baseline proteinuria and by ‘classic’ or ‘non-classic’ phenotype. Overall, 193 male patients with low (n = 135) or high (n = 58) baseline proteinuria were evaluated. Compared with patients with low baseline proteinuria, those with high baseline proteinuria had a lower mean ± standard deviation baseline eGFR (89.1 ± 26.2 vs. 106.6 ± 21.8 mL/min/1.73 m2) and faster mean ± standard error eGFR decline (−3.62 ± 0.42 vs. −1.61 ± 0.28 mL/min/1.73 m2 per year p 0.0001). Patients with classic Fabry disease had similar rates of eGFR decline irrespective of baseline proteinuria only one patient with non-classic Fabry disease had high baseline proteinuria, preventing meaningful comparisons between groups. In this analysis, baseline proteinuria significantly impacted the rate of eGFR decline in the overall population, suggesting that early treatment with good proteinuria control may be associated with renoprotective effects.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1038/GIM.2013.56
Abstract: Globotriaosylceramide concentrations were assessed as potential predictors of change from baseline after 12 months by estimated glomerular filtration rate and left-ventricular mass index using pooled data from three randomized, placebo-controlled agalsidase alfa trials and open-label extensions of patients with Fabry disease. Males (aged 18 years or older) with Fabry disease received agalsidase alfa (0.2 mg/kg every other week for 12 months). A backward-elimination approach evaluated potential predictors (baseline estimated glomerular filtration rate and left-ventricular mass index age at first dose baseline and change from baseline at 12 months of globotriaosylceramide (urine, plasma) urine protein excretion and systolic and diastolic blood pressure). Subgroups included patients randomized to placebo or agalsidase alfa (double-blind phase), then to agalsidase alfa (open-label extensions placebo→agalsidase alfa or agalsidase alfa→agalsidase alfa, respectively) and stage 2/3 chronic kidney disease patients. Baseline estimated glomerular filtration rate, age at first dose, baseline urine globotriaosylceramide excretion, and baseline and change from baseline urine protein excretion significantly predicted change from baseline estimated glomerular filtration rate in the analysis population (N = 73 all P<0.05), although not in all subgroups. Change from baseline urine and plasma globotriaosylceramide (baseline and change from baseline) concentrations did not predict change from baseline estimated glomerular filtration rate. No predictors of left-ventricular mass index were significant. Changes in globotriaosylceramide concentrations do not appear to be useful biomarkers for prediction of Fabry disease-related changes in estimated glomerular filtration rate or left-ventricular mass index.
Publisher: FapUNIFESP (SciELO)
Date: 29-07-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2012
DOI: 10.2215/CJN.03130411
Abstract: Fabry disease is a rare X-linked disease with multisystemic manifestations. This study investigated the effectiveness of long-term enzyme replacement therapy with agalsidase alfa in Fabry nephropathy treatment. In this observational study, data on patients receiving agalsidase alfa (0.2 mg/kg every other week) were extracted from the Fabry Outcome Survey, an international registry of patients with Fabry disease. Serum creatinine and estimated GFR (eGFR) at baseline and after ≥5 years of treatment were assessed 24-hour urinary protein excretion and BP measurements were also reviewed. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. Patients with an eGFR ml/min per 1.73 m 2 were excluded. Renal function was assessed in 208 patients (mean enzyme replacement therapy, 7.4 years range, 5.0–11.2 years). Mean yearly change in eGFR was −2.2 ml/min per 1.73 m 2 in men and −0.7 ml/min per 1.73 m 2 in women (95% confidence limits, −2.8 −1.7 and −1.4 0.0, respectively). Patients with 24-hour protein excretion g/24 h had poorer renal function at baseline and follow-up compared with patients with protein excretion of 500–1000 mg/24 h or with proteinuria mg/24 h. Renal function was worse in patients with baseline arterial hypertension, and there was a more rapid yearly decline compared with normotensive patients. This study suggests that long-term agalsidase alfa therapy is able to stabilize the rate of Fabry nephropathy progression in women and is associated with a mild to moderate decline of renal function in men.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.KINT.2016.10.004
Abstract: Patients with Fabry disease (FD) are at a high risk for developing chronic kidney disease and cardiovascular disease. The availability of specific but costly therapy has elevated the profile of this rare condition. This KDIGO conference addressed controversial areas in the diagnosis, screening, and management of FD, and included enzyme replacement therapy and nonspecific standard-of-care therapy for the various manifestations of FD. Despite marked advances in patient care and improved overall outlook, there is a need to better understand the pathogenesis of this glycosphingolipidosis and to determine the appropriate age to initiate therapy in all types of patients. The need to develop more effective specific therapies was also emphasized.
Publisher: Elsevier BV
Date: 11-2010
Publisher: SAGE Publications
Date: 19-09-2012
DOI: 10.5301/JN.5000214
Abstract: During Fabry disease, progressive glycosphingolipid deposition in the kidney causes gradual deterioration of renal function with proteinuria, uremia and hypertension. This results in end-stage renal disease (ESRD) which is one of the leading causes of morbidity and premature mortality in affected patients. Given the excellent graft and patient survival generally nowadays, kidney transplantation is the first choice to correct renal dysfunction and improve the overall prognosis of patients with renal failure because of Fabry disease. The benefit of enzyme-replacement therapy (ERT) in kidney transplanted Fabry patients has been controversially discussed and long-term trials focusing on the effectiveness of agalsidase in this patient population are needed.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.JACC.2010.11.018
Abstract: These analyses were designed to determine the incidence of major cardiovascular (CV) events and the natural history of CV complications in patients with Fabry disease. Fabry disease, a genetic disorder caused by deficiency of alpha-galactosidase A activity, is associated with CV dysfunction. Major CV events (myocardial infarction, heart failure, or cardiac-related death) were analyzed in 2,869 Fabry Registry patients during the natural history period (i.e., before enzyme replacement therapy or among patients who never received therapy). Multivariate logistic regression analyses were performed to identify significant predictors of CV events. Eighty-three of 1,424 men (5.8%) and 54 of 1,445 women (3.7%) experienced CV events at mean ages of 45 and 54 years, respectively. Heart failure was the most common first CV event, reported by 50 men (3.5%) and 33 women (2.3%). Hypertension and left ventricular hypertrophy were the risk factors most strongly associated with CV events. When these parameters were used as covariates in logistic regression analyses, the odds ratio (OR) for hypertension in men was 7.8 (95% confidence interval [CI]: 2.1 to 28.6, p = 0.0019), and the OR for hypertension in women was 4.5 (95% CI: 1.6 to 12.3, p = 0.0037). The OR for left ventricular hypertrophy was 4.8 in men (95% CI: 1.03 to 22.2, p = 0.0463) and 8.2 in women (95% CI: 2.6 to 26.0, p = 0.0003). Major CV events occurred in approximately 5% of Fabry Registry patients during the natural history period. All patients with Fabry disease should be monitored for possible CV risk factors, particularly hypertension and left ventricular hypertrophy.
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