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Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease.

Fervenza FC, Torra R, Warnock DG - Biologics (2008)

Bottom Line: Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of alpha-galactosidase activity.The current results are reviewed and evaluated.The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.

ABSTRACT
Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of alpha-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed.

No MeSH data available.


Related in: MedlinePlus

Distribution of proteinuria and eGFR. The median values for eGFR are shown as vertical lines, and the median 24-h urine protein is shown as horizontal lines in both panels. A) Males, n = 300, median eGFR = 81.0 mL/min/1.73 m2, and median proteinuria = 572 mg/24 h. B) Females, n = 306, median eGFR = 88.0 mL/min/1.73 m2, and median proteinuria = 180 mg/24 hr. Data from the Fabry Registry reproduced with permission from Ortiz A, Oliveira JP, Waldek S, et al 2008. Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transplant, 23:1600–7. Copyright © 2008 Oxford University Press.
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f1-btt-2-823: Distribution of proteinuria and eGFR. The median values for eGFR are shown as vertical lines, and the median 24-h urine protein is shown as horizontal lines in both panels. A) Males, n = 300, median eGFR = 81.0 mL/min/1.73 m2, and median proteinuria = 572 mg/24 h. B) Females, n = 306, median eGFR = 88.0 mL/min/1.73 m2, and median proteinuria = 180 mg/24 hr. Data from the Fabry Registry reproduced with permission from Ortiz A, Oliveira JP, Waldek S, et al 2008. Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transplant, 23:1600–7. Copyright © 2008 Oxford University Press.

Mentions: Two patient registries are now available (Fabry Registry and Fabry Outcome Survey), which contain detailed descriptions of individual patient status. Baseline assessments of age and estimated glomerular filtration rate (eGFR) for 585 adult male and 677 adult female patients from the Fabry Registry have been published (Ortiz et al 2008). Thirteen percent of adult females, and 28% of adult males had eGFR < 60 mL/min/1.73 m2 at their baseline evaluations before starting enzyme replacement therapy (ERT). Figure 1 (Ortiz et al 2008) illustrates the magnitude of proteinuria at the time of baseline evaluation for 300 male (top panel) and 306 female (bottom panel) members of the Fabry Registry cohort for whom these data were available. The horizontal lines represent the median level of proteinuria, and the vertical lines represent the median eGFR. Overt proteinuria is present at the first evaluation in the majority of patients, throughout the entire range of eGFR.


Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease.

Fervenza FC, Torra R, Warnock DG - Biologics (2008)

Distribution of proteinuria and eGFR. The median values for eGFR are shown as vertical lines, and the median 24-h urine protein is shown as horizontal lines in both panels. A) Males, n = 300, median eGFR = 81.0 mL/min/1.73 m2, and median proteinuria = 572 mg/24 h. B) Females, n = 306, median eGFR = 88.0 mL/min/1.73 m2, and median proteinuria = 180 mg/24 hr. Data from the Fabry Registry reproduced with permission from Ortiz A, Oliveira JP, Waldek S, et al 2008. Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transplant, 23:1600–7. Copyright © 2008 Oxford University Press.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2727881&req=5

f1-btt-2-823: Distribution of proteinuria and eGFR. The median values for eGFR are shown as vertical lines, and the median 24-h urine protein is shown as horizontal lines in both panels. A) Males, n = 300, median eGFR = 81.0 mL/min/1.73 m2, and median proteinuria = 572 mg/24 h. B) Females, n = 306, median eGFR = 88.0 mL/min/1.73 m2, and median proteinuria = 180 mg/24 hr. Data from the Fabry Registry reproduced with permission from Ortiz A, Oliveira JP, Waldek S, et al 2008. Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transplant, 23:1600–7. Copyright © 2008 Oxford University Press.
Mentions: Two patient registries are now available (Fabry Registry and Fabry Outcome Survey), which contain detailed descriptions of individual patient status. Baseline assessments of age and estimated glomerular filtration rate (eGFR) for 585 adult male and 677 adult female patients from the Fabry Registry have been published (Ortiz et al 2008). Thirteen percent of adult females, and 28% of adult males had eGFR < 60 mL/min/1.73 m2 at their baseline evaluations before starting enzyme replacement therapy (ERT). Figure 1 (Ortiz et al 2008) illustrates the magnitude of proteinuria at the time of baseline evaluation for 300 male (top panel) and 306 female (bottom panel) members of the Fabry Registry cohort for whom these data were available. The horizontal lines represent the median level of proteinuria, and the vertical lines represent the median eGFR. Overt proteinuria is present at the first evaluation in the majority of patients, throughout the entire range of eGFR.

Bottom Line: Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of alpha-galactosidase activity.The current results are reviewed and evaluated.The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.

ABSTRACT
Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of alpha-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed.

No MeSH data available.


Related in: MedlinePlus