Weekly Enzyme Replacement Therapy May Slow Decline of Renal Function in Patients with Fabry Disease Who Are on Long-Term Biweekly Dosing

Schiffmann, Raphael; Askari, Hasan; Timmons, Margaret; Robinson, C.; Benko, William; Brady, Roscoe O.; Ries, Markus

doi:10.1681/asn.2006111263

Cited by 115 publications

(124 citation statements)

References 35 publications

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“…42 A responder analysis for kidney function was performed comparing the final assessment to the baseline assessment using two different definitions of a responder: (1) Ͻ20% decrease in GFR and (2) no shift to a more severe state of CKD. 43 LVM was assessed by standard echocardiographic techniques and was performed by a single, experienced, boardcertified cardiologist. LVM was calculated according to the equations of Devereux 44 and was indexed to height to the 2.7 power (LVMi in g/m 2.7 ).…”

Section: Measurementsmentioning

confidence: 99%

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

Whybra

Miebach

Mengel

et al. 2009

Genetics in Medicine

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Purpose: Although Fabry disease is X linked and considered to affect primarily male hemizygotes, female heterozygotes may experience all the signs and symptoms of this metabolic disorder. This prospective, singlecenter, open-label, clinical trial was performed to evaluate the long-term response of female patients with Fabry disease to enzyme replacement therapy. Methods: Symptomatic women (average age ϭ 47 years) enrolled in this 4-year study were treated with agalsidase alfa (Replagal, Shire HGT, Inc.) at a dose of 0.2 mg/kg, every other week for 4 years (N ϭ 36). Clinical and biochemical assessments were conducted at 12-month intervals. Results: The Mainz Severity Score Index, a measure of total disease burden, was significantly reduced after 12 months (P Ͻ 0.01) of treatment and continuously improved over 4 years. Brief Pain Inventory "pain at its worst" score was reduced from 4.6 Ϯ 2.9 at baseline to 3.3 Ϯ 2.9 after 12 months (P ϭ 0.001) and remained reduced through 4 years. Mean leftventricular mass decreased from 89.4 Ϯ 29.3 g/m 2.7 at baseline to 66.5 Ϯ 29.3 g/m 2.7 after 12 months (P Ͻ 0.001) and remained reduced through 4 years. Average kidney function (estimated glomerular filtration rate and proteinuria) remained constant during the study. No safety issues were identified. Conclusions: Long-term agalsidase alfa is effective and was well tolerated in women with Fabry disease. Genet Med 2009:11(6): 441-449.

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Section: Measurementsmentioning

confidence: 99%

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

Whybra

Miebach

Mengel

et al. 2009

Genetics in Medicine

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“…When urine protein excretion was controlled to Յ0.50 g/d in patients who were treated with agalsidase-beta at 1.0 mg/kg every 2 weeks, the rate of loss of eGFR was not significantly different from 0 (29). The response was much better than previously reported for patients with overt proteinuria and eGFR Ͻ60 ml/min per m 2 (14,15,24,30) but requires confirmation in an ongoing multicenter study (31).…”

Section: Use Of Aceis and Arbs In Fabry Nephropathymentioning

confidence: 52%

“…A previous report of a single patient also described rapid loss of kidney function despite control of proteinuria with apparent stabilization of kidney function when ERT dosing was increased (16,17). The remaining patients described by Schiffmann et al (15) had higher baseline proteinuria levels and with agalsidase-alfa given at 0.2 mg/kg on a weekly basis had some improvement but still progressed at a rate of Ϫ5.5 Ϯ 4.2 ml/min per 1.73 m 2 /yr. Information is available from the Fabry Outcome Survey about the course over 3 years of 165 adult patients who were treated with agalsidase-alfa (18).…”

Section: Open-label Studies Of Ert Dosage and Frequency Of Dosingmentioning

confidence: 91%

“…The effect of dosing interval with agalsidase-alfa has been examined (15) in adult male patients with progressive decline in eGFR despite 2 to 4 years of ERT at 0.2 mg/kg agalsidase-alfa every other week. Before switching to weekly dosing, the mean decline in eGFR was Ϫ8.0 Ϯ 2.8 ml/min per 1.73 m 2 /yr.…”

Section: Open-label Studies Of Ert Dosage and Frequency Of Dosingmentioning

confidence: 99%

“…In addition, hyperkalemia and anemia and other adverse effects, such as persistent cough with ACEIs, can complicate the use of antiproteinuric therapy in patients with CKD. Recent studies of Fabry disease revealed disappointing rates of use of reninangiotensin-aldosterone system inhibitors under 50% despite multiple indications: Hypertension, proteinuria, reduced GFR, hyperfiltration, and others (14,15,17,18). This suggests that real barriers limit the use of ACEIs and ARBs in Fabry disease.…”

Section: Use Of Aceis and Arbs In Fabry Nephropathymentioning

confidence: 99%

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Enzyme Replacement Therapy and Fabry Nephropathy

Warnock

Daina

West

2010

Clinical Journal of the American Society of Nephrology

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Involvement of the kidneys in Fabry disease ("nephropathy") occurs in male and female individuals. The majority of patients with progressive nephropathy will have significant proteinuria and develop progressive loss of kidney function, leading to ESRD. All too often, treating physicians may ignore "normal" serum creatinine levels or "minimal" proteinuria and fail to assess properly the severity of kidney involvement and institute appropriate management. Fabry nephropathy is treatable, even in patients with fairly advanced disease. Although the cornerstone of therapy remains enzyme replacement therapy with agalsidase, this treatment alone does not reduce urine protein excretion. Treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors must be added to enzyme replacement therapy to reduce urine protein excretion with the hope that this will stabilize kidney function. Kidney function, with at least estimated GFR based on serum creatinine and measurements of urinary protein, should be measured at every clinic visit, and the rate of change of the estimated GFR should be followed over time. Antiproteinuric therapy can be dosed to a prespecified urine protein target rather than a specific BP goal, with the proviso that successful therapy will usually lower the BP below the goal of 130/80 mmHg that is used for other forms of kidney disease. The overall goal for treating Fabry nephropathy is to reduce the rate of loss of GFR to ؊1 ml/min per 1.73 m 2 /yr, which is that seen in the normal adult population. A systematic approach is presented for reaching this goal in the individual patient.

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Distal extremity pain as a presenting feature of Fabry's disease

Pagnini¹,

Borsini²,

Cecchi³

et al. 2011

Arthritis Care & Research

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Objective. Fabry's disease (FD) is an X-linked lysosomal storage disease. Distal extremity pain can be an early finding and renal, cardiac, and cerebrovascular complications may lead to complications and mortality. Treatment is now available for these patients, who may not be diagnosed correctly for years if the neuropathic nature of the pain is not recognized. The aim of our study was to describe early clinical features in a cohort of patients with FD and to emphasize the importance of distal extremity pain for early diagnosis. Methods. The medical charts of 35 patients with FD followed in a single center were reviewed. When data were incomplete, a detailed pain questionnaire was sent to patients. Nonresponders were contacted by telephone. Results. Distal extremity pain was present in the majority of cases (25 of 35). The mean age at diagnosis of FD was 43.5 years (range 5-77 years). Distal extremity pain was more prevalent in males than females and occurred mostly in childhood or adolescence. When present at onset, the disease progressed with subsequent organ system involvement. Misdiagnoses were frequent and included growing pains, juvenile idiopathic arthritis, connective tissue disease, and gout.

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Weekly Enzyme Replacement Therapy May Slow Decline of Renal Function in Patients with Fabry Disease Who Are on Long-Term Biweekly Dosing

Cited by 115 publications

References 35 publications

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

Enzyme Replacement Therapy and Fabry Nephropathy

Distal extremity pain as a presenting feature of Fabry's disease

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