Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults

Abstract

Progressive loss of kidney function complicates Fabry disease, an X-linked lysosomal storage disorder that arises from deficiency of alpha-galactosidase activity. Heterozygous females with Fabry disease can be as severely affected as hemizygous males, who have the classic form of the disease. Enzyme-replacement therapy with recombinant human alpha-galactosidase clears the glycosphingolipid globotriaosylceramide from kidney cells, and can stabilize renal function in adults with mild to moderate Fabry nephropathy. However, adults with more advanced nephropathy and overt proteinuria do not respond as well. For these patients, antiproteinuric therapy given in conjunction with enzyme-replacement therapy might prevent further decline in kidney function. In this Review, we propose guidelines and recommendations for the diagnosis and management of Fabry nephropathy in adults, based on published data and on the consensus of opinion of participants in the 7(th) International Fabry Nephropathy Roundtable in 2007. These organ-specific guidelines could be easier to implement than general guidelines, provided they are used in the context of an overall multisystem care approach.

Effects of Switching from Agalsidase Beta to Agalsidase Alfa in 10 Patients with Anderson-Fabry Disease

“…It has been recommended that patients receiving ERT are also prescribed angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) to reduce the risk of proteinuria (Ortiz et al 2008;Oqvist et al 2009;Mehta et al 2010;Warnock et al 2010). In our study, seven patients were receiving ACEI and/or ARB therapy.…”

The Effectiveness of Long-Term Agalsidase Alfa Therapy in the Treatment of Fabry Nephropathy

“…ERT, with either agalsidase alfa or beta, has also been shown to slow the progression of Fabry nephropathy (5)(6)(7). The current consensus is that ERT should be started in all men and in women with signs of renal involvement (8).…”

A renal variant of Fabry disease: A case with a novel Gal A hemizygote mutation

“…A natural history review of classical Fabry disease demonstrated renal involvement in 105 males and, reported that 50% of patients had proteinuria by age of 35 years and end stage renal disease by age of 47 years (4).To date, nearly 400 α-GalA gene mutations have been described (5). This patient had a novel Gal A exon 3, C to G mutation that is associated with a "renal limited variant" and expands the genotypic spectrum of Fabry with residual α-GalA activity.Despite of no cytoplasmic scroll-like myelin figures in tubular, mesangial and small artery and arteriole endothelial cells, there was segmental or global glomerulosclerosis observed in more than half of the glomeruli, which has been associated with progressive decline in GFR despite ERT (6). Furthermore, EM usually reveals lysosomal accumulation of typical myelin figure-like concentric lamellar inclusions, that may be mimicked by various drugs, such as amio- darone (7) and chloroquine (8), which this patient did not take.…”