La denervazione renale transcatetere: il ruolo del nefrologo

Studi clinici recenti hanno dimostrato che la denervazione renale bilaterale con catetere a radiofrequenza riduce significativamente i valori pressori nell'ipertensione resistente. All'efficacia antipertensiva si associa una significativa riduzione dell'ipertono simpatico, dell'insulino-resistenza e del danno d'organo cardio-renale. La procedura si è rivelata pressoché priva di effetti collaterali. Sebbene i dati della letteratura sull'efficacia antipertensiva della denervazione renale transcatetere siano solidi, solo un'analisi dell'utilizzo in campo clinico di questa metodica potrà fornire un reale parametro di giudizio sulle modalità di esecuzione della procedure nelle diverse realtà cliniche sul territorio nazionale. Per questo scopo è stato istituito il Registro Prospettico Italiano che raccoglie dati sull'efficacia e la sicurezza della denervazione renale a breve e a lungo termine. Tuttavia non sono ancora noti gli effetti della procedura sulla funzione renale, la proteinuria e il bilancio del sodio, in particolare nel lungo termine. Queste conoscenze potranno permettere di estendere le indicazioni attuali della procedura anche in altre condizioni patologiche caratterizzate da ipertono simpatico e di valutare l'impatto del costo-beneficio della denervazione renale come un potenziale trattamento alternativo alle tradizionali strategie farmacologiche

FAbry STabilization indEX (FASTEX) : an innovative tool for the assessment of clinical stabilization in Fabry disease

Two 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

The GALA project. practical recommendations for the use of migalastat in clinical practice on the basis of a structured survey among Italian experts

Background: 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

Effects of erythropoietin administration on blood pressure and urinary albumin excretion in rats

The effects of recombinant human erythropoietin (rHuEPO) administration on blood pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a week) for 6 weeks. Control animals received the vehicle only (0.25 mL of physiological saline). An angiotensin converting enzyme inhibitor was administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once a week. No significant differences in SBP were observed between rHuEPO and vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v 172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/- 7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg, respectively); UAE was significantly higher in groups treated with rHuEPO than in control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4 +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v 143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin treatment causes an increase in arterial pressure in SHR only, and an increase in UAE in both normotensive and hypertensive rats. The albuminuric effect was not entirely dependent on increased blood pressure. The treatment with an angiotensin converting enzyme inhibitor did not modify either the proteinuric or the pressor effects

redefining the pulvinar sign in fabry disease

BACKGROUND AND PURPOSE: The pulvinar sign refers to exclusive T1WI hyperintensity of the lateral pulvinar. Long considered a common sign of Fabry disease, the pulvinar sign has been reported in many pathologic conditions. The exact incidence of the pulvinar sign has never been tested in representative cohorts of patients with Fabry disease. The aim of this study was to assess the prevalence of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease cohort, determining whether relaxometry changes could be detected in this region independent of the pulvinar sign positivity. MATERIALS AND METHODS: We retrospectively analyzed brain MR imaging of 133 patients with Fabry disease recruited through specialized care clinics. A subgroup of 26 patients underwent a scan including 2 FLASH sequences for relaxometry that were compared with MRI scans of 34 healthy controls. RESULTS: The pulvinar sign was detected in 4 of 133 patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53, 7.5% of the entire male population) with renal failure and under enzyme replacement therapy. When we tested for discrepancies between Fabry disease and healthy controls in quantitative susceptibility mapping and relaxometry maps, no significant difference emerged for any of the tested variables. CONCLUSIONS: The pulvinar sign has a significantly lower incidence in Fabry disease than previously described. This finding, coupled with a lack of significant differences in quantitative MR imaging, allows hypothesizing that selective involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease

Corpus callosum involvement: a useful clue for differentiating Fabry Disease from Multiple Sclerosis.

PURPOSE: Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. METHODS: In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. RESULTS: WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. CONCLUSION: FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options

Clinicopathological characteristics of typical and atypical anti-glomerular basement membrane nephritis

Anti-glomerular basement membrane (GBM) antibody disease is a rare pathological condition that mainly involves renal and/or pulmonary parenchyma. It is characterized by the presence of circulating anti-GBM antibodies accompanied by a linear deposition of immunoglobulins (Ig) detected through immunofluorescence (IF) technique and typical signs and symptoms of organ dysfunction, such as rapidly progressive glomerulonephritis (RPGN) and pulmonary hemorrhage (PH). However, recently atypical forms of anti-GBM disease have been described and the presence of overlapping diseases contributed to make its diagnosis challenging. In this review will be discussed the entire spectrum of renal anti-GBM related conditions, focusing the attention on the differences in terms of pathogenesis, diagnosis and therapy of these disparate entities

Early recognition of airway obstruction in Fabry disease and correlation with dyspnea: A case series

BACKGROUND: 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

Routine immunohistochemical staining in membranous nephropathy : in situ detection of phospholipase A2 receptor and thrombospondin type 1 containing 7A domain

Background: Membranous nephropathy (MN) can be idiopathic (iMN) or manifest as a result of systemic underlying conditions as a secondary epiphenomenon. For the prognostic and predictive consequences of this discrimination, the routine use of reliable markers is crucial. This large MN series aimed to evaluate the routine and standardized immunohistochemical (IHC) employment of a panel of 3 biomarkers\u2014phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A), and immunoglobulin (Ig)G4\u2014in the differential diagnosis of MN forms, contributing to the validation of the technique and the correct interpretation of reproducible patterns of reactivity. Methods: We classified 95 patients with a biopsy proven diagnosis of MN as primary (n = 72) or secondary (n = 23) cases based on clinical data. After performing an IHC assay directed against PLA2R, THSD7A and IgG4 antigens, samples were interpreted by three different nephropathologists to assess the positivity/negativity of the staining according to new interpretation criteria. Results: Useful interpretation criteria were introduced to exclude false positive patterns of reactivity and to identify only true granular membranous or mesangial deposits in MN. The IHC directed against PLA2R resulted positive in 51 iMN cases and negative in 21, while 4/23 secondary forms were considered positive. Based on these data the technique showed a sensitivity of 71% and specificity of 83%. On the other hand, the IHC analysis for IgG4 resulted positive in 44 cases of iMN and negative in 28 cases, while only 4/23 secondary forms were positive (same cases positive to PLA2R). Finally, THSD7A was found to be positive only in 1 case, which was negative to PLA2R and IgG4. The combination of the results allowed a classification of the series into two major groups: \u201cdouble-positive\u201d (PLA2R+/IgG4+/THSD7A 12) and \u201ctriple-negative\u201d (PLA2R 12/IgG4 12/THSD7A 12) cases. Conclusions: Based on these data, the diagnostic performance of the three biomarkers used in a \u201ctandem fashion\u201d can reach 79% sensitivity and 83% specificity, significantly reducing the risk of a false-positive or false-negative result and improving the routine characterization of this frequent glomerulonephritis