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Renal Manifestations of Fabry Disease

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Fabry Disease

Abstract

The majority of Fabry patients have kidney involvement (nephropathy), with significant proteinuria and progressive loss of kidney function leading to end-stage-renal-disease. Baseline assessment of the severity of Fabry nephropathy, institution of appropriate therapy, and close monitoring of the subsequent course is essential. Once present, target kidney damage is not reversed, so stopping further progression is the treatment goal. Fabry nephropathy is treatable, even in patients with fairly advanced disease. While the cornerstone of therapy remains enzyme replacement therapy with agalsidase preparations, this treatment alone does not reduce urine protein excretion. Treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be added to enzyme replacement therapy to reduce urine protein excretion with the goal that this will stabilize kidney function. Kidney function, with estimated glomerular filtration rate based on serum creatinine, and measurements of urinary protein should be obtained at every clinic visit, and the rate of loss of function followed over time. Anti-proteinuric therapy can be dosed to a pre-specified urine protein target rather than a specific blood pressure goal, recognizing that successful therapy will usually lower the blood pressure below the goal of 130/80 mmHg used for other forms of kidney disease. The overall goal for treating Fabry nephropathy is to reduce the rate of loss of glomerular filtration rate to ≤ −1.0 ml/min/1.73 m2/year, which is that seen in the normal adult population.

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Abbreviations

ACEI:

Angiotensin converting enzyme inhibitor

ARB:

Angiotensin receptor blocker

CKD:

Chronic kidney disease

eGFR:

Estimated GFR

EM:

Electron microscopy

ESRD:

End-stage renal disease

ERT:

Enzyme replacement therapy

GFR:

Glomerular filtration rate

GLA :

The α-galactosidase A locus

GL-3:

Globotriaosylceramide

mGFR:

Measured GFR

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, University of Alabama, Birmingham, AL, USA

    David G. Warnock

  2. Departments of Pathology, Medicine and Human Genetics, Faculty of Medicine, Hospital São João, Porto, Portugal

    Carmen Valbuena & João Paulo Oliveira

  3. Department of Medicine, Dalhousie University, Halifax, Canada

    Michael West

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  1. David G. Warnock
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  2. Carmen Valbuena
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  3. Michael West
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  4. João Paulo Oliveira
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Correspondence to David G. Warnock .

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  1. , Shaare Zedek Medical Center, Gaucher Clinic, Bayit Street 12, Jerusalem, 91034, Israel

    Deborah Elstein

  2. , Shaare Zedek Medical Center, Genetics Unit, Bayit Street 12, Jerusalem, 91031, Israel

    Gheona Altarescu

  3. University of Mainz, Children's Hospital, Langenbeckstrasse 1, Mainz, 55131, Germany

    Michael Beck

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Warnock, D.G., Valbuena, C., West, M., Oliveira, J.P. (2010). Renal Manifestations of Fabry Disease. In: Elstein, D., Altarescu, G., Beck, M. (eds) Fabry Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9033-1_12

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