Global reach of over 20 years of experience in the patient-centered Fabry Registry: Advancement of Fabry disease expertise and dissemination of real-world evidence to the Fabry community

Wanner, Christoph; Ortíz, Alberto; Wilcox, William R.; Hopkin, Robert J.; Johnson, J.; Ponce, Elvira; Ebels, Johan T.; Batista, Julie L.; Maski, Manish; Politei, Juan; Martins, Ana María; Banikazemi, Maryam; Linhart, Aleš; Mauer, Michael; Oliveira, João Paulo de; Weidemann, Frank; Germain, Dominique P.

doi:10.1016/j.ymgme.2023.107603

Cited by 11 publications

(3 citation statements)

References 64 publications

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“…These key findings contradict expectations that ERT would reduce renal complications (26,29,30). Instead, in vivo 37: 2609-2617 (2023) Fabry nephropathy and associated morbidity climbed steeply over the past two decades, especially among higher-risk subgroups.…”

Section: Discussionmentioning

confidence: 85%

Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients

TSAI,

WANG,

CHIANG

et al. 2023

In Vivo

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Background/Aim: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and associated urinary tract complications. Enzyme replacement therapy (ERT) has been available since 2001, but contemporary real-world data are lacking regarding Fabry nephropathy risks and treatment outcomes. Patients and Methods: This retrospective cohort study analyzed electronic medical records data for 10,637 Fabry disease patients from the TriNetX research database. Kidney and urinary tract outcomes were evaluated over two decades, 2000-2010 and 2011-2020. Outcomes assessed included chronic kidney disease (CKD), urinary tract infections, urinary incontinence, obstruction, renal insufficiency, and endstage renal disease (ESRD). Results: The prevalence of stage 4-5 CKD nearly doubled between 2000-2010 and 2011-2020, while ESRD prevalence rose over 4-fold. Incidence rates showed similar marked elevations across renal and urologic complications. Females and Black patients experienced disproportionate escalations in kidney and urinary tract morbidity. Conclusion: This large cohort study revealed significantly increased Fabry nephropathy and associated urologic complications over the past two decades, contradicting expectations of reduced morbidity with ERT availability. The findings highlight needs to optimize screening, treatment strategies, monitoring practices, and address disparities to curb rising disease burden and improve patient outcomes.Fabry disease results from mutations in the X-linked GLA gene encoding the lysosomal enzyme α-galactosidase A (α-Gal A) (1). Loss of α-Gal A activity leads to progressive accumulation of neutral glycosphingolipids, mainly globotriaosylceramide (GL-3), in lysosomes of cells throughout the body (2-4). GL-3 accumulation and downstream inflammatory and fibrotic 2609

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Section: Discussionmentioning

confidence: 85%

Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients

TSAI,

WANG,

CHIANG

et al. 2023

In Vivo

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“…By week 24, statistically significant improvements were observed [40] . Additionally, utilizing the Fabry Outcome Survey database, Hoffmann et al observed a reduction in the prevalence of gastrointestinal symptoms following agalsidase alfa at both 12 and 24 months [41] .…”

Section: Specific Therapymentioning

confidence: 99%

Gastrointestinal involvement in Fabry disease

Politei,

Solar

2024

Rare Dis Orphan Drugs J

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Fabry disease is an X-linked lysosomal storage disorder due to alpha-galactosidase A deficiency. This deficiency results in a progressive accumulation of globotriaosylceramide and related glycosphingolipids, particularly in vascular endothelial cells, renal cells, nerve cells, and cardiomyocytes. Gastrointestinal symptoms are frequent and can be extremely debilitating. It is known that most of the well-characterized gastrointestinal manifestations of Fabry disease are the result of the accumulation of glycosphingolipids, which causes vascular occlusion and malfunction of the peripheral and autonomic nervous system. Although improvement is noted in treating patients with enzyme replacement therapy and migalastat, some continue to experience symptoms after treatment; thus, it remains a significant cause of morbidity, necessitating concurrent adjuvant treatment. Current research is focused on clarifying the underlying dysmotility and further analyzing the correlation between the gut-brain axis, the histologic disease progression, and the clinical symptom presentation.

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“…Analysis of two large Fabry disease registries enabled the long-term follow-up of patients receiving enzyme replacement therapy and comparison of their changes in kidney function with historical cohorts of untreated patients. These analyses showed that the treatment slowed the rate of kidney function decline in these patients, thus proving that the recombinant enzyme therapy is nephroprotective [ 162 , 163 ]. Migalastat is a relatively new drug, but a recent 30-month follow-up of patients with sensitive mutations has shown the long-term stabilization of renal function in patients receiving oral migalastat, similar to patients previously receiving recombinant agalsidase enzyme therapy [ 164 ].…”

Section: Disease/diagnosis-specific Nephroprotection (Adpkd Fabry Dis...mentioning

confidence: 99%

Pharmacological Nephroprotection in Non-Diabetic Chronic Kidney Disease—Clinical Practice Position Statement of the Polish Society of Nephrology

Stompór

Adamczak

Kurnatowska

et al. 2023

JCM

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Chronic kidney disease (CKD) is a modern epidemic worldwide. Introducing renin–angiotensin system (RAS) inhibitors (i.e., ACEi or ARB) not only as blood-pressure-lowering agents, but also as nephroprotective drugs with antiproteinuric potential was a milestone in the therapy of CKD. For decades, this treatment remained the only proven strategy to slow down CKD progression. This situation changed some years ago primarily due to the introduction of drugs designed to treat diabetes that turned into nephroprotective strategies not only in diabetic kidney disease, but also in CKD unrelated to diabetes. In addition, several drugs emerged that precisely target the pathogenetic mechanisms of particular kidney diseases. Finally, the role of metabolic acidosis in CKD progression (and not only the sequelae of CKD) came to light. In this review, we aim to comprehensively discuss all relevant therapies that slow down the progression of non-diabetic kidney disease, including the lowering of blood pressure, through the nephroprotective effects of ACEi/ARB and spironolactone independent from BP lowering, as well as the role of sodium–glucose co-transporter type 2 inhibitors, acidosis correction and disease-specific treatment strategies. We also briefly address the therapies that attempt to slow down the progression of CKD, which did not confirm this effect. We are convinced that our in-depth review with practical statements on multiple aspects of treatment offered to non-diabetic CKD fills the existing gap in the available literature. We believe that it may help clinicians who take care of CKD patients in their practice. Finally, we propose the strategy that should be implemented in most non-diabetic CKD patients to prevent disease progression.

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Global reach of over 20 years of experience in the patient-centered Fabry Registry: Advancement of Fabry disease expertise and dissemination of real-world evidence to the Fabry community

Cited by 11 publications

References 64 publications

Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients

Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients

Gastrointestinal involvement in Fabry disease

Pharmacological Nephroprotection in Non-Diabetic Chronic Kidney Disease—Clinical Practice Position Statement of the Polish Society of Nephrology

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