Cardiovascular outcomes in Fabry disease are linked to severity of chronic kidney disease

Talbot, Andrew; Lewis, Nigel; Nicholls, Kathy

doi:10.1136/heartjnl-2014-306278

Cited by 43 publications

(37 citation statements)

References 30 publications

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“…One has severe LVH with cardiac fibrosis and a significant renal failure, while the other has severe LVH, but does not present cardiac fibrosis or clinical evidence of renal involvement by Fabry disease, which supports the notion that the development of cardiac manifestations is also dependent on age and renal function [19]. …”

Section: Discussionsupporting

confidence: 51%

Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease

Azevedo

Gago²,

Miltenberger-Miltényi³

et al. 2017

Cardiology

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We report on the clinical, biochemical, and genetic findings of a large family with the classical phenotype of Fabry disease due to the novel nonsense mutation c.607G>T (p.E203X) of the GLA gene, which occurs in the active site of the α-galactosidase A enzyme. This report highlights that (i) Fabry disease diagnosis should be considered in all cases of unexplained left ventricular hypertrophy (LVH), even in its milder forms; (ii) a complete evaluation of patients with unexplained LVH is important to find diagnostic red flags of treatable causes of LVH, such as Fabry disease; (iii) cascade family screening is paramount to the earlier diagnosis and treatment of other affected family members; and (iv) the Fabry disease phenotype is highly variable in heterozygote females, even within the same family.

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Section: Discussionsupporting

confidence: 51%

Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease

Azevedo

Gago²,

Miltenberger-Miltényi³

et al. 2017

Cardiology

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“…Deposition of undergraded glycosphingolipid substrate occur in all kidney cells and structures including podocytes, mesangial, tubular, interstitial and vascular endothelial cells [3]. Fabry nephropathy is linked to cardiovascular morbidity and mortality in FD patients [4]. Although males have more severe Fabry disease than females, heterozygous females with X-chromosomal inactivation can also be severely affected depending on random X-chromosomal inactivation [5].…”

Section: Introductionmentioning

confidence: 99%

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

Nowak¹,

Koch²,

Huynh‐Do³

et al. 2017

Kidney Blood Press Res

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Background/Aims: Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype. Methods: The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 – 54] years for females and 39 [28 – 49] years for males. Results: A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year. Conclusion: Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function.

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“…Class 5 chronic kidney disease (CKD5) was associated with worse baseline cardiac parameters and progressive LVH. LVMI increased by 35.4 AE 31.8 g/m 2.7 in CKD5 vs. 5.7 AE 7.9 g/m 2.7 in non-CKD5 (P ¼ 0.044), and cardiovascular events (including sudden death, arrhythmia and pacing device insertion) occurred in 100% of patients with CKD5 (21 events) compared with 26% in non-CKD5 patients (seven events) [32]. However, the type of mutation does not appear to be associated with cardiac outcome.…”

Section: Cardiac Featuresmentioning

confidence: 90%

Fabry disease

Hughes

2016

Current Opinion in Cardiology

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Cardiovascular outcomes in Fabry disease are linked to severity of chronic kidney disease

Cited by 43 publications

References 30 publications

Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the <b><i>GLA</i></b> Gene Associated with the Classical Phenotype of Fabry Disease

Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the <b><i>GLA</i></b> Gene Associated with the Classical Phenotype of Fabry Disease

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease

Fabry disease

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