87 research outputs found
FP_Supplemental_revised_Tables_4.2019 – Supplemental material for Tumour incidence in Fabry disease: A cross-sectional study
No full textSupplemental material, FP_Supplemental_revised_Tables_4.2019 for Tumour incidence in Fabry disease: A cross-sectional study by Federica Rossi, Sara Auricchio, Agnese Binaggia, Vincenzo L’imperio, Fabio Pagni and Federico Pieruzzi in Journal of Onco-Nephrology</p
Statistical_method_Fabry_Cancer1 – Supplemental material for Tumour incidence in Fabry disease: A cross-sectional study
No full textSupplemental material, Statistical_method_Fabry_Cancer1 for Tumour incidence in Fabry disease: A cross-sectional study by Federica Rossi, Sara Auricchio, Agnese Binaggia, Vincenzo L’imperio, Fabio Pagni and Federico Pieruzzi in Journal of Onco-Nephrology</p
Correction to: Outcomes on safety and efficacy of left atrial appendage occlusion in end stage renal disease patients undergoing dialysis (Journal of Nephrology, (2021), 34, 1, (63-73), 10.1007/s40620-020-00774-5)
No full textThe article Outcomes on safety and efficacy of left atrial appendage occlusion in end stage renal disease patients undergoing dialysis, written by Simonetta Genovesi, Luca Porcu, Giorgio Slaviero, Gavino Casu, Silvio Bertoli, Antonio Sagone, Monique Buskermolen, Federico Pieruzzi, Giovanni Rovaris, Alberto Montoli, Jacopo Oreglia, Emanuela Piccaluga, Giulio Molon, Mario Gaggiotti, Federica Ettori, Achille Gaspardone, Roberto Palumbo, Francesca Viazzi, Marco Breschi, Maurizio Gallieni, Gina Contaldo, Giuseppe D’Angelo, Pierluigi Merella, Fabio Galli, Paola Rebora, Mariagrazia Valsecchi, and Patrizio Mazzone, was originally published electronically on the publisher’s internet portal on 6 June 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 10 July 2020 to © The Author(s) 2020 and this article is licensed under a Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/ by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The original article has been updated
The GALA project: practical recommendations for the use of migalastat in clinical practice on the basis of a structured survey among Italian experts
No full textBackground Oral migalastat has recently been approved for the treatment of Anderson-Fabry disease (FD) in patients aged >= 16 years with amenable mutations on the basis of two phase III trials, FACETS and ATTRACT. However, with the introduction of migalastat into clinical practice, it is important to correctly identify the patients who may gain the most benefits from this therapy. Due to the relatively recent availability of migalastat, its role in clinical practice still has to be included in guidelines or recommendations. On these bases, a multidisciplinary group of Italian Experts in the treatment of FD has run the GALA project, with the aim to collect the opinions of expert physicians and to propose some starting points for an experience-based use of migalastat. Results Overall, although studies and data from longer-term follow-up with migalastat are still emerging, available evidence is consistent in showing that this molecule does represent a suitable therapy for the treatment of FD, in patients aged >= 16 years and with amenable mutations. The use of migalastat as an oral option appears to be overall safe, and experience thus far indicates potential for improving quality of life, controlling GI symptoms, stabilizing renal function and reducing cardiac hypertrophy. Conclusion Migalastat can be considered either as a first-line therapy - given its efficacy, extensive tissue penetration, convenient oral regimen, and the current limited therapeutic options available - or in patients on enzyme-replacement therapy (ERT) who experience side effects, with poor compliance to chronic i.v. therapy, or with clinical evidence of progression of the disease
Angiotensin II modulates calponin gene expression in rat vascular smooth muscle cells in vivo.
No full textIt has been shown that angiotensin II (Ang II) induces the expression of calponin, a 34 kD actin-binding protein, in vascular smooth muscle cells in vitro. The aim of this study was to investigate whether Ang II can modulate calponin gene expression in rat aorta in vivo. Aortic calponin gene expression was studied after chronic exogenous Ang II administration and in Goldblatt hypertension. To investigate the effect of Ang II administration, Sprague Dawley rats were treated for 6 days with a continuous infusion of Ang II (200 ng/kg per min) or saline by osmotic minipumps. The effect of endogenous Ang II on aortic calponin mRNA expression was studied in Goldblatt hypertensive rats with (2K1C model), or without (1K1C model) activation of the renin-angiotensin system. In particular, calponin gene expression in 2K1C rats was studied both at 1 week (2K1C-HR, high renin) and 4 weeks after the onset of hypertension, when plasma renin activity (PRA) was returned to normal values (2K1C-NR, normal renin). Systolic blood pressure (SBP) was measured twice a week. At the end of the experimental period, PRA was measured by radioimmunoassay, and aortic calponin gene expression was measured by Northern hybridization. SBP was significantly higher (P < 0.01), whereas PRA was suppressed (P < 0.01), in Ang II versus saline-treated rats. Northern hybridization showed that the aortic calponin gene expression significantly increased (2.5-fold) in Ang II-treated rats (P = 0.01). In Goldblatt hypertensive rats, SBP was significantly higher in 2K1C-HR (P < 0.01), 2K1C-NR (P < 0.01) and 1K1C (P < 0.01) rats compared with the corresponding sham-treated rats. Activation of the renin-angiotensin system was present only in 2K1C-HR rats (P < 0.01), and Northern analysis showed that aortic calponin mRNA expression was significantly increased (2.2-fold) in this group of rats only (P < 0.01). Our data demonstrate that both exogenous and endogenous Ang II increase calponin gene expression in aortic smooth muscle cells, independently of the hemodynamic effect of Ang II
α-Gal A missense variants associated with Fabry disease can lead to ER stress and induction of the unfolded protein response
No full textAnderson-Fabry Disease (FD) is an X-linked lysosomal disorder caused by mutations in GLA, the gene encoding the lysosomal hydrolase α-galactosidase A (α-Gal A), leading to accumulation of glycosphingolipids in the lysosomes. FD is a multisystemic disorder leading to progressive cardiovascular, cerebrovascular and kidney dysfunction. Phenotypes are divided in two main classes, classic or non-classic, depending on substrate accumulation, age at onset, disease manifestation, severity and progression. The more severe classical phenotype is generally associated with mutations leading to absent or strongly reduced α-Gal A activity, while mutations with higher residual activity generally lead to the non-classical one. Approximately 70% of the over 1,000 Fabry disease-associated mutations are missense mutations, some leading to endoplasmic reticulum (ER) retention of mutant protein. We hypothesized that such mutations could be associated, besides the well-known absence of α-Gal A function/activity, to a possible gain of function effect due to production of a misfolded protein. We hence expressed α-Gal A missense mutations in HEK293 GLA(−/−) cells and investigated the localization of mutant protein and induction of ER stress and of the unfolded protein response (UPR). We selected a panel of 7 missense mutations, including mutants shown to have residual or no activity in vitro. Immunofluorescence analysis showed that mutants with residual activity have decreased lysosomal localization compared with wild type, and partial retention in the ER, while missense mutants with no residual activity are fully retained in the ER. UPR (ATF6 branch) was significantly induced by all but two mutants, with clear correlation with the extent of ER retention and the predicted mutation structural effect. These data identify a new molecular pathway, associated with gain of function effect, possibly involved in pathogenesis of FD
FAbry STabilization indEX (FASTEX) : an innovative tool for the assessment of clinical stabilization in Fabry disease
No full textTwo disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R (2) = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients
Early recognition of airway obstruction in Fabry disease and correlation with dyspnea: A case series
No full textBACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disease that mainly affects kidney, heart and the nervous system, but a respiratory involvement, in the form of obstructive airway disease, has also been described.
METHODS: We performed a complete evaluation of pulmonary functional tests (PFTs) on 18 consecutive adult patients with FD. In our cohort we identified 5 subjects with main airway obstruction, but only 2 had airway obstruction in absence of causes other than FD.
RESULTS: We found in the majority of patients early signs of airway obstruction, including small-airway obstruction, mild to moderate lung hyperinflation and mild to moderate increase in specific airway resistance. Lung hyperinflation (expressed as increased residual volume at plethysmography) was positively correlated with the presence of dyspnea (both at rest and after exertion).
CONCLUSIONS: Therefore complete PFTs, which can detect early signs of airway obstruction, may be considered as a useful screening tool for patients with FD, particularly for those presenting with dyspnea
Respiratory involvement in Fabry disease
No full textFabry disease is an inherited lysosomal storage disease affecting kidney, heart and nervous system. Respiratory involvement has been described, but complete evaluation of pulmonary functional tests (PFTs) has not been yet performed. Our aim is to evaluate the presence and severity of PFTs alteration in adult patients with Fabry disease.
A prospective observational study was performed in adults with Fabry disease referring to the Nephrology clinic of San Gerardo Hospital, Monza, Italy, from 2010 to 2012. Medical history and complete PFTs were recorded for each patient. Percentage of predicted for PFT values was considered. Results are expressed as median [IQR].
16 patients were enrolled (5 male; median age 48 yrs). Among those, 3 were previous and 1 active smoker (median pack/years 4), 3 had asthma, 6 received enzyme replacement therapy (ERT). 5 patients (31%) presented Forced Expiratory Volume in 1 second (FEV1) mildly decreased (2.1L [1.3-2.8], 81% [44-92]) and a FEV1/FVC ratio<70%, 3 of them (19% of total) had no risk factors for airway obstruction.
In 10 subjects (63%), specific Airway Resistance (sRAW) and Residual Volume (RV) were increased (152% [133-171] and 140% [131-152], respectively), while Total Lung Capacity (TLC) was normal in all patients (107% [94-114]). Middle Expiratory Flow (MEF) at 75%, MEF50% and MEF25% were slightly decreased (86.5% [79-103], 78.5% [62-100] and 76.5% [57-96], respectively).
A minority of patients had airway obstruction, defined as FEV1/FVC<70%, in absence of causes other than Fabry disease. Slight alterations, as increased sRAW, lung hyperinflation and small-airway obstruction, are present in the majority. Complete PFTs could be useful to detect early signs of airway obstruction in these patients
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