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

Relationship between baseline proteinuria and the rate of loss of estimated glomerular filtration rate (eGFR) in the phase III extension study. The participants were sub-grouped based on their baseline proteinuria, which was determined before entry into the double-blinded initial phase of the study. During the 54-month treatment period, patients (n = 10) with baseline urinary protein/creatinine ratios > 1.0 had a mean rate of decline of eGFR of −7.4 mL/min/1.73 m2/year. In contrast, patients (n = 42) with baseline urinary protein/creatinine ratios < 1.0 had a mean rate of decline of eGFR of −1.0 mL/min/1.73 m2/year. 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


getmorefigures.php?uid=PMC2727881&req=5

f10-btt-2-823: Relationship between baseline proteinuria and the rate of loss of estimated glomerular filtration rate (eGFR) in the phase III extension study. The participants were sub-grouped based on their baseline proteinuria, which was determined before entry into the double-blinded initial phase of the study. During the 54-month treatment period, patients (n = 10) with baseline urinary protein/creatinine ratios > 1.0 had a mean rate of decline of eGFR of −7.4 mL/min/1.73 m2/year. In contrast, patients (n = 42) with baseline urinary protein/creatinine ratios < 1.0 had a mean rate of decline of eGFR of −1.0 mL/min/1.73 m2/year. 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: The long-term results (54 months) for 58 patients who completed the phase III study of agalsidase-beta have recently been described. Following the initial 20-week double-blind phase, all 58 patients were transitioned to an open-label extension study, and received agalsidase-beta at 1 mg/kg every other week for as long as an additional 54 months (Germain et al 2007). Median serum creatinine and eGFR were relatively unchanged at the end of 54 months of open-label therapy for 42 patients whose baseline proteinuria was less than 1 g/day. The initial eGFR averaged 138 mL/min/1.73 m2, and the mean progression rate (eg, loss of eGFR) was −1.005 ± 0.970 [SEM] mL/min/1.73 m2/year (Figure 10). In contrast, 10 patients had rapid progression (rate = −7.399 ± 1,858 [SEM] m:/min/1.73 m2/year) despite relatively normal eGFR at baseline (average = 100 mL/min/1.73 m2). Two characteristics separated those with rapid progression from the majority who did not progress: the baseline proteinuria exceeded 1 g/day and the kidney biopsies revealed focal or global glomerular sclerosis in at least 50% of the glomeruli (Germain et al 2007).


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 the rate of loss of estimated glomerular filtration rate (eGFR) in the phase III extension study. The participants were sub-grouped based on their baseline proteinuria, which was determined before entry into the double-blinded initial phase of the study. During the 54-month treatment period, patients (n = 10) with baseline urinary protein/creatinine ratios > 1.0 had a mean rate of decline of eGFR of −7.4 mL/min/1.73 m2/year. In contrast, patients (n = 42) with baseline urinary protein/creatinine ratios < 1.0 had a mean rate of decline of eGFR of −1.0 mL/min/1.73 m2/year. 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

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

f10-btt-2-823: Relationship between baseline proteinuria and the rate of loss of estimated glomerular filtration rate (eGFR) in the phase III extension study. The participants were sub-grouped based on their baseline proteinuria, which was determined before entry into the double-blinded initial phase of the study. During the 54-month treatment period, patients (n = 10) with baseline urinary protein/creatinine ratios > 1.0 had a mean rate of decline of eGFR of −7.4 mL/min/1.73 m2/year. In contrast, patients (n = 42) with baseline urinary protein/creatinine ratios < 1.0 had a mean rate of decline of eGFR of −1.0 mL/min/1.73 m2/year. 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: The long-term results (54 months) for 58 patients who completed the phase III study of agalsidase-beta have recently been described. Following the initial 20-week double-blind phase, all 58 patients were transitioned to an open-label extension study, and received agalsidase-beta at 1 mg/kg every other week for as long as an additional 54 months (Germain et al 2007). Median serum creatinine and eGFR were relatively unchanged at the end of 54 months of open-label therapy for 42 patients whose baseline proteinuria was less than 1 g/day. The initial eGFR averaged 138 mL/min/1.73 m2, and the mean progression rate (eg, loss of eGFR) was −1.005 ± 0.970 [SEM] mL/min/1.73 m2/year (Figure 10). In contrast, 10 patients had rapid progression (rate = −7.399 ± 1,858 [SEM] m:/min/1.73 m2/year) despite relatively normal eGFR at baseline (average = 100 mL/min/1.73 m2). Two characteristics separated those with rapid progression from the majority who did not progress: the baseline proteinuria exceeded 1 g/day and the kidney biopsies revealed focal or global glomerular sclerosis in at least 50% of the glomeruli (Germain et al 2007).

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