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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

Relationship between baseline proteinuria and probability of a renal outcome event in the phase III extension study. Baseline proteinuria (expressed as the urinary protein/creatinine ratio) was determined before entry into the double-blinded initial phase of the study. Logistic regression analysis was used to determine the probability of a renal event (defined as 50% increase in serum creatinine compared to pre-treatment value, with the increased value >1.4 mg/dL). Adapted with permission from Germain D, Waldek S, Banikazemi M, et al 2007. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol, 18:1547–57. Copyright © 2007 American Society of Nephrology.
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f9-btt-2-823: Relationship between baseline proteinuria and probability of a renal outcome event in the phase III extension study. Baseline proteinuria (expressed as the urinary protein/creatinine ratio) was determined before entry into the double-blinded initial phase of the study. Logistic regression analysis was used to determine the probability of a renal event (defined as 50% increase in serum creatinine compared to pre-treatment value, with the increased value >1.4 mg/dL). Adapted with permission from Germain D, Waldek S, Banikazemi M, et al 2007. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol, 18:1547–57. Copyright © 2007 American Society of Nephrology.

Mentions: Proteinuria has emerged as a major determinant in the development of progressive tubular injury, interstitial fibrosis, and GFR loss in CKD (Remuzzi et al 2006), as well as Fabry nephropathy (Schiffmann 2007; Warnock 2007). Higher baseline levels of proteinuria are associated with more rapid decline of renal function (Breunig et al 2006; Banikazemi et al 2007; Germain et al 2007; Schiffmann et al 2007). The relationship between baseline proteinuria and the future occurrence of adverse kidney outcomes, even in patients with relatively mild Fabry nephropathy is depicted in Figure 9. At the initial assessment, the finding of significant proteinuria is a call for action, both for institution of effective ERT and control of proteinuria with ACEIs and ARBS. Elevated urinary protein excretion is a common finding in Fabry disease (Figure 1), and along with measurement of serum creatinine and calculation of eGFR, are integral elements of the clinical assessment of Fabry nephropathy (Ortiz et al 2008).


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

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

Relationship between baseline proteinuria and probability of a renal outcome event in the phase III extension study. Baseline proteinuria (expressed as the urinary protein/creatinine ratio) was determined before entry into the double-blinded initial phase of the study. Logistic regression analysis was used to determine the probability of a renal event (defined as 50% increase in serum creatinine compared to pre-treatment value, with the increased value >1.4 mg/dL). Adapted with permission from Germain D, Waldek S, Banikazemi M, et al 2007. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol, 18:1547–57. Copyright © 2007 American Society of Nephrology.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2727881&req=5

f9-btt-2-823: Relationship between baseline proteinuria and probability of a renal outcome event in the phase III extension study. Baseline proteinuria (expressed as the urinary protein/creatinine ratio) was determined before entry into the double-blinded initial phase of the study. Logistic regression analysis was used to determine the probability of a renal event (defined as 50% increase in serum creatinine compared to pre-treatment value, with the increased value >1.4 mg/dL). Adapted with permission from Germain D, Waldek S, Banikazemi M, et al 2007. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol, 18:1547–57. Copyright © 2007 American Society of Nephrology.
Mentions: Proteinuria has emerged as a major determinant in the development of progressive tubular injury, interstitial fibrosis, and GFR loss in CKD (Remuzzi et al 2006), as well as Fabry nephropathy (Schiffmann 2007; Warnock 2007). Higher baseline levels of proteinuria are associated with more rapid decline of renal function (Breunig et al 2006; Banikazemi et al 2007; Germain et al 2007; Schiffmann et al 2007). The relationship between baseline proteinuria and the future occurrence of adverse kidney outcomes, even in patients with relatively mild Fabry nephropathy is depicted in Figure 9. At the initial assessment, the finding of significant proteinuria is a call for action, both for institution of effective ERT and control of proteinuria with ACEIs and ARBS. Elevated urinary protein excretion is a common finding in Fabry disease (Figure 1), and along with measurement of serum creatinine and calculation of eGFR, are integral elements of the clinical assessment of Fabry nephropathy (Ortiz 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