Kidney biopsy findings in heterozygous Fabry disease females with early nephropathy

Valbuena, Carmen; Carvalho, Elísio; Bustorff, Manuela; Ganhão, Mariana; Relvas, Sandra; Nogueira, Rosete; Carneiro, Fátima; Oliveira, João Paulo

doi:10.1007/s00428-008-0653-2

Cited by 38 publications

(48 citation statements)

References 45 publications

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“…A range of kidney biopsy studies have been undertaken to gain a better understanding of the natural history of Fabry nephropathy [8,[12][13][14][15] and to evaluate the response to enzyme replacement therapy (ERT) [16][17][18]. Fogo et al aimed to standardize the reading of kidney biopsies and quantification of the histological alterations [15].…”

Section: Introductionmentioning

confidence: 99%

“…Glomerular filtration rate gradually declines and classically affected males progress to end-stage renal disease before their fifth decade [4][5][6][7]. A spectrum of histological lesions can be observed in the kidneys, even in cases with normal glomerular filtration rate and minimal proteinuria [8][9][10][11][12][13][14][15]. These lesions may include intracellular GSL deposits and nonspecific chronic glomerular, vascular, and tubulointerstitial fibro-sclerotic lesions.…”

Section: Introductionmentioning

confidence: 99%

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Kidney histologic alterations in α-Galactosidase-deficient mice

et al. 2011

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Fabry disease is a rare X-linked disorder caused by mutations in the α-galactosidase gene (GLA), the resultant deficiency of lysosomal α-galactosidase enzyme activity leading to systemic accumulation of globotriaosylceramide and other glycosphingolipids. GLA knockout mice ("Fabry mice") were generated as an animal model for Fabry disease but, as they do not manifest progressive chronic kidney disease (CKD), their relevance as a model for human Fabry nephropathy is uncertain. We evaluated the histological alterations in the kidneys of Fabry mice at different ages, as contrasted to those observed in wild-type mice. Furthermore, we compared the renal histological alterations of Fabry mice to the kidney pathology reported in patients with Fabry disease at comparable age ranges and across different CKD stages, using a scoring system that has been developed for Fabry nephropathy. Fabry mice are phenotypically different from wild-type mice, displaying progressive age-related accumulation of glycosphingolipids in all types of renal cells. There were no statistically significant differences between Fabry mice and Fabry patients in the prevalence of glycosphingolipid storage per renal cell type with the exceptions of mesangial (higher in humans) and proximal tubular cells (higher in mice). However, Fabry mice lack the nonspecific histological glomerulosclerotic and interstitial fibrotic renal lesions that best correlate with progressive CKD in Fabry patients, and do not develop large podocyte inclusions. We postulate that the elucidation of the mechanisms underlying these species differences, may contribute important clues to a better understanding of the pathogenesis of Fabry nephropathy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kidney histologic alterations in α-Galactosidase-deficient mice

et al. 2011

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“…It has been hypothesized that the overloading of lysosomes with Gb3 simply leads to the apoptosis of the cell 15 . Another theory argues that the inflammation process is related to the accumulation of Gb3.…”

Section: Cellular Physiopathologymentioning

confidence: 99%

Fabry Cardiomyopathy: A Global View

cebada¹,

Magnas²,

Zamorano³

2011

Advances in the Study of Genetic Disorders

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“…Kidney biopsies show globotriaosylceramide (GL-3) accumulation in tubular epithelial cells, glomerular and endothelial cells, and vascular smooth muscle cells (1)(2)(3)(4)(5). With time, progressive GL-3 accumulation leads to microvascular dysfunction, occlusion, and ischemia, with subsequent development of tubular atrophy, segmental and global sclerosis, and interstitial fibrosis (6 -8).…”

Section: What Do We Know?mentioning

confidence: 99%

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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Kidney biopsy findings in heterozygous Fabry disease females with early nephropathy

Cited by 38 publications

References 45 publications

Kidney histologic alterations in α-Galactosidase-deficient mice

Kidney histologic alterations in α-Galactosidase-deficient mice

Fabry Cardiomyopathy: A Global View

Enzyme Replacement Therapy and Fabry Nephropathy

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