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Background Patients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes. Methods The European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage. Results Among 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2–7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage. Conclusions This study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic.

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.

*Square Project: V.M. Agate (Palmanova, UD), A.M. Anelli (Pistoia), L. Apicella (Salerno), D. Avino (Vairano Scalo, CE), Y. Battaglia (Ferrara), P.L. Bedani (Ferrara), G. Bellinghieri (Messina), A.M. Bernardi (Rovigo), C. Bonifati (Corato, BA), M. Borzumati (Verbania), P.L. Botti (Mantova), M. Brigante (Campobasso), F. Brighina (San Nicola La Strada, CE), P. Calzavara (Conegliano, TV), C. Caputo (Albenga, SV), F. Cardone (Lavello, PZ), F. Cavatorta (Imperia), N. Confessore (Scafati, SA), M. Cossu (Sassari), E. Costantino (Gavardo, BS), G. Costantino (Messina), L. D’Apice (Caserta), R. D’Arcangelo (Arzano, NA), F. Dagostino (Corato, BA), A. Dal Canton (Pavia), G. Delgado (Teano, CE), R. Di Pietro (Napoli), C. Esposito (Pavia), P. Esposito (Pavia), E. Fasianos (Altamura, BA), F. Fiorini (Rovigo), P. Galeotti (Viterbo), G. Garibotto (Genova), A. Gemelli (Rovigo), M.C. Gregorini (Reggio Emilia), P. Iuliano (Benevento), L. La Peccerella (Benevento), M. Liuzzi (Benevento), M. Merola (Sorrento, NA), C. Montesano (Imperia), L.F. Morrone (Benevento), M. Napoli (Galatina, LE), F. Napolitano (Corato, BA), S. Paglia (Lavello, PZ), M. Parravano (Sora, FR), S. Pasquali (Reggio Emilia), A. Rosa (Benevento), M.L. Sambati (Taranto), P. Schiavone (Brindisi), E. Sozzo (Galatina, LE), A. Storari (Ferrara), R. Tarchini (Mantova), G. Tirino (Montesarchio, BN), L. Turchetta (Sora, FR). School Project: G. Bellinghieri (Messina), G. Beltrame (Torino), M. Bozzi (Bari), E. Casolino (Rionero in Vulture, PZ), E. Centrone (Ruvo di Puglia, BA), M. Ciccarelli (Reggio Calabria), T. Cicchetti (Rossano, CS), C. Colturi (Sondrio), E. Costantino (Gavardo, BS), G. Costantino (Messina), F. Dagostino (Corato, BA), E. Fasianos (Altamura, BA), P. Galeotti (Viterbo), Garibotto (Genova), F. Indraccolo (S. Fermo della Battaglia, CO), M. Lombardi (Borgo S. Lorenzo, FI), C. Minoretti (S. Fermo della Battaglia, CO), F. Napolitano (Corato, BA), R. Parsi (Alcamo, TP), F. Petrarulo (Bari), E. Prati (Desenzano del Garda, BS), F. Quarello (Torino), V. Rondanini (Palmi, RC), D. Russo (Barletta), P. Tira (Manerbio, BS), S. Turina (Manerbio, BS), W.D. Valentini (Rieti) WORLD KIDNEY DAY

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme &alpha, galactosidase A (&alpha, Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the &alpha, Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. &alpha, Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, &alpha, Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.

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.

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.

Background: The FAbry STabilization indEX (FASTEX) is an innovative index allowing the assessment of clinical stability over time in Fabry disease patients. This index was developed in a population of 28 male patients with the classical form of Fabry disease. Objectives: The aim of the study was to test the accuracy of the FASTEX in evaluating Fabry disease stability in 132 male and female patients with classical and non-classical Fabry disease from nine Italian centres and it also aimed to define the sensitivity and specificity of this new tool. In particular, we aimed to investigate the correlation between the FASTEX and clinical judgement in a large-scale cohort of the study population. Methods: Statistical methods applied to this investigation included the calculation of accuracy, specificity and sensitivity, receiver operating characteristic (ROC) curves and Cohen’s j index related to the FASTEX and clinical judgement. Results: The patient population included 58 males (43.9%). The mean age of the overall population was 46.3 6 15. 1 years (range 31.2–61.4). The median interval between the two multidisciplinary evaluations used for FASTEX calculation was 398 days. Since no gold standard method is available to define the overall clinical condition of Fabry patients over time, the results of the FASTEX were compared with clinical judgements given by the physicians involved in this study. In this way, the FASTEX classified 121 of 132 (92%) patients correctly. In particular, the FASTEX correctly identified 93% (41/44) of clinically ‘unstable’ and 91% (80/88) of clinically ‘stable’ patients. The area under the curve of the ROC related to the FASTEX index cut-off (20) was equal to 0.967, very close to its theoretical maximum (1), which means that it is an excellent test for classifying patients as ‘stable’ or ‘unstable’ compared with clinical judgement. In addition, the FASTEX cut-off >20 provides themost acceptable balance between sensitivity and specificity. The Cohen’s j index value obtained in our study was 0.82, showing a highly statistically significant P-value

Introduction: World Kidney Day (WKD) was promoted by the Italian Kidney Foundation and the Italian Society of Nephrology for raising awareness, detection, prevention, and treatment of kidney diseases. The Italian WKD focused on the “School Project” by screening students attending the fifth year of high school. The main goal of the “School Project” was to assess in healthy adolescents the presence of hypertension (HTN) and proteinuria; as well as to evaluate potential interrelations between overweight, obesity (both measured with different anthropometric methods), blood pressure (BP) levels, and proteinuria. The ancillary goal was to have an estimate of awareness on some nephrology topics. Methods: The study population consisted of 17- to 19-year-old students. HTN was defined as systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg. Isolated systolic hypertension (ISH) was defined as SBP ≥140 mm Hg and DBP 120 mm Hg but 80 mm Hg but

Aims Fabry cardiomyopathy is characterized by glycosphingolipid storage and increased myocardial trabeculation has also been demonstrated. This study aimed to explore by cardiac magnetic resonance whether myocardial trabecular complexity, quantified by endocardial border fractal analysis, tracks phenotype evolution in Fabry cardiomyopathy. Methods and results Study population included 20 healthy controls (12 males, age 32±9) and 45 Fabry patients divided into three groups: 15 left ventricular hypertrophy (LVH)-negative patients with normal T1 (5 males, age 28±13; Group 1); 15 LVH-negative patients with low T1 (9 males, age 33±9.6; Group 2); 15 LVH-positive patients (11 males, age 53.5±9.6; Group 3). Trabecular fractal dimensions (Dfs) (total, basal, mid-ventricular, and apical) were evaluated on cine images. Total Df was higher in all Fabry groups compared to controls, gradually increasing from controls to Group 3 (1.27±0.02 controls vs. 1.29±0.02 Group 1 vs. 1.30±0.02 Group 2 vs. 1.34±0.02 Group 3; P Conclusion Fabry cardiomyopathy is characterized by a progressive increase in Df of endocardial trabeculae together with shortening of T1 values. Myocardial trabeculation is increased before the presence of detectable sphingolipid storage, thus representing an early sign of cardiac involvement.

Anderson-Fabry disease (AFD) cardiomyopathy is characterized by glycosphingolipid (Gb3) storage in all cellular components, with consequent left ventricular hypertrophy (LVH). Gb3 accumulation also involves atrial myocytes ([1][1]), ultimately leading to left atrial (LA) enlargement and reduced

Background Fabry's disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A, and is difficult to diagnose. Although parapelvic cysts (PC) were previously associated with FD, their prevalence and significance are unclear. Methods The present study aimed to: (i) evaluate, by renal ultrasound, the real prevalence of PC and of their determinants in a multicentre, nationwide cohort of FD patients (n = 173, Study 1) and (ii) ascertain whether a greater accuracy of PC detection improved their identification, in FD patients from a single centre (n = 67, Study 2). In both studies, for each FD patient, an age- and renal function-matched subject was selected for comparison (1:1). Results In Study 1, PC were detected in 28.9% of FD subjects and in only 1.1% of control subjects (P

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance +/- SD: baseline, 328 +/- 96 m; 6 months, 367 +/- 113 m) but not in the control group (baseline, 321 +/- 107 m; 6 months, 324 +/- 116 m; P

World Kidney Day (WKD) was conceived in 2003 to inform the general population of the fact that chronic kidney disease is a global, public health threat that frequently occurs with no symptoms, and which can be treated with early detection using simple and inexpensive methods (1). The need for a WKD devoted to kidney diseases arises also from the knowledge that most people are unaware of their blood pressure and the potential presence of abnormalities in their urine. Indeed, some surveys have shown that less than 5% of the general population know where the kidneys are located and what they do (1). The Fondazione Italiana del Rene (FIR; National Kidney Foundation of Italy), in collaboration with the Italian Society of Nephrology and the Red Cross of Italy, has organized, for the general population, a nationwide project of evaluation of blood pressure and urine tests every year on WKD. The results of this project have already been reported (2, 3). During WKD in 2008 and 2009, evaluation of blood pressure and a urine test were carried out in students attending the fourth and fifth year of Italian high school in many Italian cities. This is a unique initiative in the context of those carried out around the world by countries that have observed WKD. The relevance of this screening relies on the fact that this population is seldom evaluated by either pediatricians or general practitioners in the absence of overt disease. Paradoxically, adolescents, having a longer life expectancy than adults, are more exposed to risk factors (3). Therefore, early detection of their urinary abnormalities and/or abnormal blood pressure levels allows action to be taken to reduce the risk of irreversible disease years later.

Background/Aims: High BMI increases the risk of cardiovascular events (CVEs) in the general population. Conflicting results have been reported on the role of BMI on CVEs and on decline of renal function in patients with chronic kidney disease not on dialysis (CKD). This study evaluates the impact of BMI on CVEs, dialysis initiation, and coronary artery calcification (CAC) in CKD patients. Methods: CKD patients were divided in normal-BMI and high-BMI patients. CVEs, initiation of dialysis, and extent and progression of CAC were assessed. Univariate and multivariable analysis were performed (adjustment variables: age, diabetes, hypertension, gender, CKD stage, serum concentration of hemoglobin, parathyroid hormone, calcium, phosphorus, albumin, C-reactive protein, LDL-cholesterol, total calcium score, 24-hour proteinuria). Patients were followed to the first event (CVE, dialysis) or for 2 years. Results: 471 patients were evaluated. A CVE occurred in 13.5 and 21.3% (p < 0.05) of normal-BMI and high-BMI patients, respectively. High BMI did not increase the risk for CVEs in univariate (HR: 1.86; 95% CI: 0.97-3.54; p = 0.06) or multivariable analysis (HR: 1.36; 95% CI: 0.57-3.14; p = 0.50). High BMI did not increase the risk for initiation of dialysis in univariate (HR: 0.96; 95% CI: 0.58-1.60; p = 0.9) or multivariable analysis (HR: 1.77; 95% CI: 0.82-3.81; p = 0.14). Adding the interaction term (between BMI and glomerular filtration rate) to other variables, the risk of dialysis initiation significantly increased (HR: 3.06; 95% CI: 1.31-7.18; p = 0.01) in high-BMI patients. High BMI was not a predictor of CAC extent or progression. Conclusions: High BMI was not a predictor of CVEs. High BMI increased the risk for dialysis initiation, but high BMI was not associated to CAC extent and progression. The presence of confounders may underestimate the impact of high BMI on dialysis initiation.

We tested for the presence of coronary calcifications in patients with chronic renal disease not on dialysis and studied its progression in 181 consecutive non-dialyzed patients who were followed for a median of 745 days. Coronary calcifications (calcium score) were tallied in Agatston units by computed tomography, and the patients were stratified into two groups by their baseline calcium score (100 U or less and over 100 U). Survival was measured by baseline calcium score and its progression. Cardiac death and myocardial infarction occurred in 29 patients and were significantly more frequent in those patients with calcium scores over 100 U (hazard ratio of 4.11). With a calcium score of 100 U or less, the hazard ratio for cardiac events was 0.41 and 3.26 in patients with absent and accelerated progression, respectively. Thus, in non-dialyzed patients, the extent of coronary calcifications was associated to cardiac events, and progression was an independent predictive factor of cardiac events mainly in less calcified patients. Hence, assessment of coronary calcifications and progression might be useful for earlier management of risk factors and guiding decisions for prevention of cardiac events in this patient population.

FGF23 is a bone-derived hormone that plays an important role in the regulation of phosphate and 1,25-dihydroxy vitamin D metabolism. FGF23 principally acts in the kidney to induce urinary phosphate excretion and suppress 1,25-dihydroxyvitamin D synthesis in the presence of FGF receptor 1 (FGFR1) and its coreceptor Klotho. In patients with chronic kidney disease (CKD), circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to hypersecretion of parathyroid hormone. Furthermore, FGF23 is associated with vascular dysfunction, atherosclerosis, and left ventricular hypertrophy. This paper summarizes the role of FGF23 in the pathogenesis of mineral, bone, and cadiovascular disorders in CKD.

Coronary artery calcification is more prevalent in dialysis patients than in patients without kidney disease and this is associated with high serum phosphorus. In this study, we evaluate the effect of calcium carbonate or sevelamer treatments on the progression of calcification in 90 predialysis patients. Inclusion criteria were stable serum calcium, phosphorus, parathyroid hormone, and a similar baseline total calcium score (TCS). These patients were not treated by phosphate binder, vitamin D, or statin. They were given low-phosphorus diets without or with daily calcium carbonate or sevelamer throughout the study that averaged 2 years. Baseline demographic or clinical characteristics along with biochemical parameters were not different among the three groups. The TCS significantly increased in patients on the low-phosphorus diet alone, to a lesser extent in calcium carbonate-treated patients, and not at all in sevelamer-treated patients. The progression of coronary calcification paralleled that of the calcium score. Our study shows that sevelamer treatment should not be restricted to dialysis patients; however, a larger study should be undertaken to confirm these results.