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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

Effects of agalsidase-beta on rate of loss of kidney function in a 36-year-old male with Fabry nephropathy. Creatinine clearance was measured at the indicated points, and enzyme replacement therapy (1 mg/kg every 2 weeks) was started in early 2001. During the entire follow-up period, there were no major changes in blood pressure or proteinuria (0.4–0.6 g). The patient was started on 5 mg lisinopril in 1994. Because of persistent cough, irbesartan at 150 mg/day was substituted in for lisinopril in December 2001. Reproduced with permission from De Schoenmakere G, Chauveau D, Grunfeld JP. 2003. Enzyme replacement therapy in Anderson-Fabry’s disease: beneficial clinical effect on vital organ function. Nephrol Dial Transplant, 18:33–5. Copyright © 2003 Oxford University Press.
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f2-btt-2-823: Effects of agalsidase-beta on rate of loss of kidney function in a 36-year-old male with Fabry nephropathy. Creatinine clearance was measured at the indicated points, and enzyme replacement therapy (1 mg/kg every 2 weeks) was started in early 2001. During the entire follow-up period, there were no major changes in blood pressure or proteinuria (0.4–0.6 g). The patient was started on 5 mg lisinopril in 1994. Because of persistent cough, irbesartan at 150 mg/day was substituted in for lisinopril in December 2001. Reproduced with permission from De Schoenmakere G, Chauveau D, Grunfeld JP. 2003. Enzyme replacement therapy in Anderson-Fabry’s disease: beneficial clinical effect on vital organ function. Nephrol Dial Transplant, 18:33–5. Copyright © 2003 Oxford University Press.

Mentions: Currently, there are two forms of ERT available for the treatment of Fabry disease: (1) Replagal® (agalsidase-alfa; Shire Human Genetic Therapies, Inc., Cambridge, MA) and (2) Fabrazyme® (agalsidase-beta; Genzyme Corporation, Inc., Cambridge, MA). With the exception of the structures of the oligosaccharide side chains, the primary amino acid sequences of these products are the same (Blom et al 2003). The approved doses of agalsidase-alfa and agalsidase-beta are 0.2 mg/kg and 1.0 mg/kg, given intravenously every 2 weeks, respectively. Agalsidase-beta has been approved for the treatment of Fabry disease in the US, while both agents are available for clinical use in other countries (Desnick 2004). The overall experience with ERT has been very encouraging (Barbey et al 2008). Figure 2 illustrates the effect of ERT in a male Fabry patient with moderately severe nephropathy in whom proteinuria was controlled with irbesartan (De Schoenmakere et al 2003); the rate of loss of kidney function was reduced by 67%. Earlier reports with agalsidase-alfa given at 0.2 mg/kg every other week to male Fabry patients with relatively mild disease were also encouraging (Barbey et al 2008).


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

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

Effects of agalsidase-beta on rate of loss of kidney function in a 36-year-old male with Fabry nephropathy. Creatinine clearance was measured at the indicated points, and enzyme replacement therapy (1 mg/kg every 2 weeks) was started in early 2001. During the entire follow-up period, there were no major changes in blood pressure or proteinuria (0.4–0.6 g). The patient was started on 5 mg lisinopril in 1994. Because of persistent cough, irbesartan at 150 mg/day was substituted in for lisinopril in December 2001. Reproduced with permission from De Schoenmakere G, Chauveau D, Grunfeld JP. 2003. Enzyme replacement therapy in Anderson-Fabry’s disease: beneficial clinical effect on vital organ function. Nephrol Dial Transplant, 18:33–5. Copyright © 2003 Oxford University Press.
© Copyright Policy
Related In: Results  -  Collection

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

f2-btt-2-823: Effects of agalsidase-beta on rate of loss of kidney function in a 36-year-old male with Fabry nephropathy. Creatinine clearance was measured at the indicated points, and enzyme replacement therapy (1 mg/kg every 2 weeks) was started in early 2001. During the entire follow-up period, there were no major changes in blood pressure or proteinuria (0.4–0.6 g). The patient was started on 5 mg lisinopril in 1994. Because of persistent cough, irbesartan at 150 mg/day was substituted in for lisinopril in December 2001. Reproduced with permission from De Schoenmakere G, Chauveau D, Grunfeld JP. 2003. Enzyme replacement therapy in Anderson-Fabry’s disease: beneficial clinical effect on vital organ function. Nephrol Dial Transplant, 18:33–5. Copyright © 2003 Oxford University Press.
Mentions: Currently, there are two forms of ERT available for the treatment of Fabry disease: (1) Replagal® (agalsidase-alfa; Shire Human Genetic Therapies, Inc., Cambridge, MA) and (2) Fabrazyme® (agalsidase-beta; Genzyme Corporation, Inc., Cambridge, MA). With the exception of the structures of the oligosaccharide side chains, the primary amino acid sequences of these products are the same (Blom et al 2003). The approved doses of agalsidase-alfa and agalsidase-beta are 0.2 mg/kg and 1.0 mg/kg, given intravenously every 2 weeks, respectively. Agalsidase-beta has been approved for the treatment of Fabry disease in the US, while both agents are available for clinical use in other countries (Desnick 2004). The overall experience with ERT has been very encouraging (Barbey et al 2008). Figure 2 illustrates the effect of ERT in a male Fabry patient with moderately severe nephropathy in whom proteinuria was controlled with irbesartan (De Schoenmakere et al 2003); the rate of loss of kidney function was reduced by 67%. Earlier reports with agalsidase-alfa given at 0.2 mg/kg every other week to male Fabry patients with relatively mild disease were also encouraging (Barbey et al 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