Limits...
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

Annualized change in estimated glomerular filtration rate (mL/min/1.73 m2/year ± SD) in patients treated with agalsidase-alfa at 0.2 mg/kg every 2 weeks (left bars) followed by weekly treatment (right bars). Patients are stratified by baseline proteinuria: <0.3 g/day, black bars; >1 g/day, open bars. Adapted with permission from Schiffmann R, Askari H, Timmons M, et al 2007. Weekly enzyme replacement therapy may slow decline of renal function in Fabry patients who are on long-term biweekly dosing. J Am Soc Nephrol, 18:1576–83. Copyright © 2007 American Society of Nephrology.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2727881&req=5

f3-btt-2-823: Annualized change in estimated glomerular filtration rate (mL/min/1.73 m2/year ± SD) in patients treated with agalsidase-alfa at 0.2 mg/kg every 2 weeks (left bars) followed by weekly treatment (right bars). Patients are stratified by baseline proteinuria: <0.3 g/day, black bars; >1 g/day, open bars. Adapted with permission from Schiffmann R, Askari H, Timmons M, et al 2007. Weekly enzyme replacement therapy may slow decline of renal function in Fabry patients who are on long-term biweekly dosing. J Am Soc Nephrol, 18:1576–83. Copyright © 2007 American Society of Nephrology.

Mentions: The effect of dosing interval with agalsidase-alfa has been examined (Schiffmann et al 2007); a group of adult males patients who had progressive decline in eGFR despite 2 to 4 years of 0.2 mg/kg agalsidase-alpha therapy every other week, were 0.2 mg/kg agalsidase-alfa every week. (It should be noted that this is an “off-label” use of agalsidase-alfa.) Before switching to weekly dosing, the mean decline in eGFR was −8.0 ± 2.8 (SD) mL/min/1.73 m2/year. Four patients with low baseline proteinuria (average = 222.8 ± 60 [SD] mg/day) progressed on agalsidase-alfa given every other week at a rate of −6.6 ± 2.1 mL/min/1.73 m2 per year. After switching to weekly dosing of agalsidase-alfa, these 4 patients had an improvement in their kidney function (Figure 3). The remaining patients with higher baseline proteinuria levels had some improvement in the rate of decline of their kidney function, but still progressed at a rate of −5.5 ± 4.2 (SD) mL/min/1.73 m2 per year on 0.2 mg/kg agalsidase-alfa given on a weekly basis (Figure 3).


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

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

Annualized change in estimated glomerular filtration rate (mL/min/1.73 m2/year ± SD) in patients treated with agalsidase-alfa at 0.2 mg/kg every 2 weeks (left bars) followed by weekly treatment (right bars). Patients are stratified by baseline proteinuria: <0.3 g/day, black bars; >1 g/day, open bars. Adapted with permission from Schiffmann R, Askari H, Timmons M, et al 2007. Weekly enzyme replacement therapy may slow decline of renal function in Fabry patients who are on long-term biweekly dosing. J Am Soc Nephrol, 18:1576–83. Copyright © 2007 American Society of Nephrology.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2727881&req=5

f3-btt-2-823: Annualized change in estimated glomerular filtration rate (mL/min/1.73 m2/year ± SD) in patients treated with agalsidase-alfa at 0.2 mg/kg every 2 weeks (left bars) followed by weekly treatment (right bars). Patients are stratified by baseline proteinuria: <0.3 g/day, black bars; >1 g/day, open bars. Adapted with permission from Schiffmann R, Askari H, Timmons M, et al 2007. Weekly enzyme replacement therapy may slow decline of renal function in Fabry patients who are on long-term biweekly dosing. J Am Soc Nephrol, 18:1576–83. Copyright © 2007 American Society of Nephrology.
Mentions: The effect of dosing interval with agalsidase-alfa has been examined (Schiffmann et al 2007); a group of adult males patients who had progressive decline in eGFR despite 2 to 4 years of 0.2 mg/kg agalsidase-alpha therapy every other week, were 0.2 mg/kg agalsidase-alfa every week. (It should be noted that this is an “off-label” use of agalsidase-alfa.) Before switching to weekly dosing, the mean decline in eGFR was −8.0 ± 2.8 (SD) mL/min/1.73 m2/year. Four patients with low baseline proteinuria (average = 222.8 ± 60 [SD] mg/day) progressed on agalsidase-alfa given every other week at a rate of −6.6 ± 2.1 mL/min/1.73 m2 per year. After switching to weekly dosing of agalsidase-alfa, these 4 patients had an improvement in their kidney function (Figure 3). The remaining patients with higher baseline proteinuria levels had some improvement in the rate of decline of their kidney function, but still progressed at a rate of −5.5 ± 4.2 (SD) mL/min/1.73 m2 per year on 0.2 mg/kg agalsidase-alfa given on a weekly basis (Figure 3).

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