Development of a filter paper method potentially applicable to mass and high‐risk urinary screenings for Fabry disease

Auray‐Blais, Christiane; Cyr, Denis; Mills, Kevin; Giguère, Robert; Drouin, Régen

doi:10.1007/s10545-006-0444-3

Cited by 41 publications

(17 citation statements)

References 20 publications

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“…Urine or plasma Gb 3 concentrations have been used as biomarkers for diagnostic purposes and to follow the effect of specific therapies such as ERT. 1,2 In addition, the measurement of plasma Gb 3 concentration was used as a pharmacodynamic marker to demonstrate the biological activity of agalα in vivo. 20 For patients with elevated plasma or urine Gb 3 concentrations before treatment, ERT resulted in an initial drop in Gb 3 concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] Plasma Gb 3 concentration has been found to be consistently elevated in hemizygous males with classic Fabry disease but variably elevated in some variant hemizygous males with residual enzyme activity and in heterozygous females. 5,6 No evidence has been published supporting the use of plasma or urine Gb 3 concentrations as a biomarker for disease progression or response to treatment.…”

Section: Original Research Articlementioning

confidence: 99%

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Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa

Schiffmann¹,

Ries

Blankenship

et al. 2013

Genetics in Medicine

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Original research articleGlobotriaosylceramide (Gb 3 ) is often elevated in the urine of patients with Fabry disease, 1 and some studies support its use as a diagnostic biomarker. [2][3][4] Plasma Gb 3 concentration has been found to be consistently elevated in hemizygous males with classic Fabry disease but variably elevated in some variant hemizygous males with residual enzyme activity and in heterozygous females. 5,6 No evidence has been published supporting the use of plasma or urine Gb 3 concentrations as a biomarker for disease progression or response to treatment. For patients with elevated plasma or urine Gb 3 concentrations before treatment, enzyme replacement therapy (ERT) results in an initial drop in Gb 3 concentrations. 5,7 The lower Gb 3 concentrations do not remain low in all patients and do not always coincide with clinical improvement. 8 Biomarkers are generally defined as measurements that reflect the activity of a disease process 9 and can be (i) prognostic, (ii) predictive, or (iii) pharmacodynamic. 10 The goal of this study was to assess the relationship of plasma and urine Gb 3 concentrations with renal or cardiac outcome measures. A previous analysis of pooled data from three randomized, placebo-controlled clinical trials and their open-label extensions (sponsored by Shire Human Genetic Therapies) of male patients with Fabry disease suggested a stabilizing effect of agalsidase alfa (agalα) on renal function assessed by measured glomerular filtration rate (GFR). 11 In that analysis, baseline GFR or elevated proteinuria category (≥1 g/24 h) significantly predicted GFR decline during treatment. Using a suitable selection approach of pooled data Purpose: 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.Methods: 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.Results: 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...

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Section: Discussionmentioning

confidence: 99%

Section: Original Research Articlementioning

confidence: 99%

Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa

Schiffmann¹,

Ries

Blankenship

et al. 2013

Genetics in Medicine

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“…Gb 3 is clearly useful as a diagnostic marker for individual patients and probably for screening for the disease in populations of patients at risk (2,6,15,16). It can be used as an indicator of the metabolic effect of infused ␣-galactosidase A for ERT (17,18).…”

Section: What Do We Know?mentioning

confidence: 99%

Biomarkers of Fabry Disease Nephropathy

Schiffmann¹,

Waldek²,

Benigni³

et al. 2010

Clinical Journal of the American Society of Nephrology

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It is suggested that biomarkers of renal complications of Fabry disease are likely to be useful for diagnosis and to follow the natural disease progression or the effect of specific therapeutic interventions. Traditionally, globotriaosylceramide (Gb 3 ) in urine has been used to evaluate the effect of specific therapy, such as enzyme replacement therapy (ERT). Although urinary Gb 3 decreases significantly with ERT, it has not yet been shown to be a valid surrogate marker in treatment trials. We propose a detailed study of the nature and origin of Gb 3 combined with a prospective collaborative trial that combines Gb 3 changes with the effect of ERT on clinical nephrological outcome measures. Existing biomarkers such as general proteinuria/ albuminuria or specific proteins such as N-acetyl-␤-D-glucosaminidase should be evaluated along with novel proteomic or metabolomic studies for biomarker discovery using mass spectrometry or nuclear magnetic resonance. Standard scoring of all pathologic aspects of kidney biopsies may also be a promising way to assess the effect of therapy.

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“…In this study, we used the filter paper method suggested by C. Auray-Blais et al which has the following advantages 5 . First, contrary to existing Gb3 techniques, which are both time-and labor-intensive, this filter paper method eliminates the lipid extraction, glycolipid isolation, centrifugation and evaporation steps, while maintaining the sensitivity and efficiency.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the urinary globotriaosylceramide (Gb3) assay by tandem mass spectrometry

Song

Park

et al. 2010

Mol. Cell. Toxicol.

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Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from a deficiency of α-galactosidase A, which leads to the progressive accumulation of one biomarker, globotriaosylceramide (Gb3), prominently elevated in the urine of affected patients. Using filter paper discs saturated with urine, we evaluated the analytical performance and clinical usefulness of the urinary Gb3 assay by tandem mass spectrometry (LC-MS/MS), with respect to linearity, precision, and reproducibility. We used healthy control urine samples to validate the reference interval of urinary Gb3. This method showed a good linearity (R 2 = = 0.9998) in the range of 0.05-10 μg/mL. Within-run CVs were less than 5% and total CVs were within 10%. The mean recovery of Gb3 from the urine filter paper was 96.7% and the limit of quantification (S/N›5) was 0.05 μg/mL, which was sensitive enough for the diagnosis of FD. The mean concentration of Gb3 in urine samples from healthy Korean controls was 5.93 ±3.6 μg/mmol Cr (range 0.9-16.43 μg/mmol Cr). The urinary Gb3 assay by LC-MS/MS showed good analytical performance required for the diagnosis of FD in its linearity, precision, and accuracy. Therefore, this technique could be used for a rapid and reliable first line screening, monitoring and/or diagnosis of individuals at high risk for FD.

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Development of a filter paper method potentially applicable to mass and high‐risk urinary screenings for Fabry disease

Cited by 41 publications

References 20 publications

Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa

Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa

Biomarkers of Fabry Disease Nephropathy

Evaluation of the urinary globotriaosylceramide (Gb3) assay by tandem mass spectrometry

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