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Background and Purpose: Alterations of the basilar artery (BA) anatomy have been suggested as a possible MRA feature of Fabry disease (FD). Nonetheless, no information about their clinical or pathophysiologic correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD., Materials and Methods: Brain MRIs of 53 subjects with FD (mean age, 40.7 [SD, 12.4] years; male/female ratio = 23:30) were collected in this single-center study. Mean BA diameter and its tortuosity index were calculated on MRA. Possible correlations between these metrics and clinical, laboratory, and advanced imaging variables of the posterior circulation were tested. In a subgroup of 20 subjects, a 2-year clinical and imaging follow-up was available, and possible longitudinal changes of these metrics and their ability to predict clinical scores were also probed., Results: No significant association was found between MRA metrics and any clinical, laboratory, or advanced imaging variable ( P values ranging from -0.006 to 0.32). At the follow-up examination, no changes were observed with time for the mean BA diameter ( P = .84) and the tortuosity index ( P = .70). Finally, baseline MRA variables failed to predict the clinical status of patients with FD at follow-up ( P = .42 and 0.66, respectively)., Conclusions: Alterations of the BA in FD lack of any meaningful association with clinical, laboratory, or advanced imaging findings collected in this study. Furthermore, this lack of correlation seems constant across time, suggesting stability over time. Taken together, these results suggest that the role of BA dolichoectasia in FD should be reconsidered., (© 2024 by American Journal of Neuroradiology.)

Background: The nephrotoxic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are widely acknowledged. In particular, diclofenac is the most commonly prescribed NSAIDs, but no previous findings of electrolyte disturbances were reported following its administration., Case Report: We presented the case of a man who experienced significant weakness associated with severe deficiencies in potassium, calcium, and magnesium after misusing diclofenac because of severe back pain., Conclusions: This case emphasizes the need of awareness about the electrolyte imbalances and electrolyte disturbances associated with the misuse of diclofenac, which is a widely available drug. This is a case report which does not need a Clinical Trial Number., (© 2024. The Author(s).)

Purpose: How to measure brain globotriaosylceramide (Gb3) accumulation in Fabry Disease (FD) patients in-vivo is still an open challenge. The objective of this study is to provide a quantitative, non-invasive demonstration of this phenomenon using quantitative MRI (qMRI)., Methods: In this retrospective, monocentric cross-sectional study conducted from November 2015 to July 2018, FD patients and healthy controls (HC) underwent an MRI scan with a relaxometry protocol to compute longitudinal relaxation rate (R1) maps to evaluate gray (GM) and white matter (WM) lipid accumulation. In a subgroup of 22 FD patients, clinical (FAbry STabilization indEX -FASTEX- score) and biochemical (residual α-galactosidase activity) variables were correlated with MRI data. Quantitative maps were analyzed at both global ("bulk" analysis) and regional ("voxel-wise" analysis) levels., Results: Data were obtained from 42 FD patients (mean age = 42.4 ± 12.9, M/F = 16/26) and 49 HC (mean age = 42.3 ± 16.3, M/F = 28/21). Compared to HC, FD patients showed a widespread increase in R1 values encompassing both GM (p FWE  = 0.02) and WM (p FWE  = 0.02) structures. While no correlations were found between increased R1 values and FASTEX score, a significant negative correlation emerged between residual enzymatic activity levels and R1 values in GM (r = -0.57, p = 0.008) and WM (r = -0.49, p = 0.03)., Conclusions: We demonstrated the feasibility and clinical relevance of non-invasively assessing cerebral Gb3 accumulation in FD using MRI. R1 mapping might be used as an in-vivo quantitative neuroimaging biomarker in FD patients., (© 2024. The Author(s).)

Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group ( p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure ( p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.

Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressive and multisystemic and is characterized by early symptoms and late complications (renal, cardiac and neurological dysfunction). Fatigue and exercise intolerance are early common symptoms in FD patients but the specific causes are still to be defined. In this narrative review, we deal with the contribution of cardiac and pulmonary dysfunctions in determining fatigue and exercise intolerance in FD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 De Marco, Gambardella, Bianco, Fiordelisi, Cerasuolo, Buonaiuto, Avvisato, Capuano, Amicone, Di Risi, Riccio, Spinelli, Pisani, Iaccarino and Sorriento.)

Introduction: Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations., Methods: We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2 h after the main meal for the evaluation of postprandial potassium concentrations., Results: Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41 mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36 mmol/L; p = 0.15)., Conclusions: In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Fabry disease (FD) is caused by mutations in the galactosidase alpha (GLA) gene which lead to the accumulation of globotriaosylceramide (Gb-3). Enzyme replacement therapy (ERT) and oral chaperone therapy are the current pharmacological treatments for this condition. However, in the literature, there is a growing emphasis on exploring non-pharmacological therapeutic strategies to improve the quality of life of patients with FD. In particular, the nutritional approach to FD has been marginally addressed in the scientific literature, although specific dietary interventions may be useful for the management of nephropathy and gastrointestinal complications, which are often present in patients with FD. Especially in cases of confirmed diagnosis of irritable bowel syndrome (IBS), a low-FODMAP diet can represent an effective approach to improving intestinal manifestations. Furthermore, it is known that some food components, such as polyphenols, may be able to modulate some pathogenetic mechanisms underlying the disease, such as inflammation and oxidative stress. Therefore, the use of healthy dietary patterns should be encouraged in this patient group. Sports practice can be useful for patients with multi-organ involvement, particularly in cardiovascular, renal, and neurological aspects. Therefore, the aim of this review is to summarize current knowledge on the role of nutrition and physical activity in FD patients.

Background: Physical exercise (PE) can regulate inflammation, cardiovascular health, sarcopenia, anaemia, and bone health in the chronic kidney disease (CKD) population. Experimental and clinical studies both help us better understand the mechanisms that underlie the beneficial effects of the exercise, especially in renal anaemia and CKD-mineral bone disorders (CKD-MBDs). Here, we summarize this evidence, exploring the biological pathways involved, locally released substances, and crosstalk between tissues, but also the shortcomings of current knowledge., Summary: Anaemia: Both in healthy and CKD subjects, PE may mimic hypoxia, inhibiting PHDs; so hydroxylate HIF-α subunits may be translocated into the nucleus, resulting in dimerization of HIF-1α and HIF-1β, recruitment of p300 and CBP, and ultimately, binding to HREs at target genes to cause activation. However, in CKD subjects acute PE causes higher levels of lactate, leading to iron restriction by upregulating hepatic hepcidin expression, while chronic PE allows an increased lactate clearance and HIF-α and VEGFα levels, stimulating both erythropoiesis and angiogenesis., Ckd-Mbd: PE may improve bone health decreasing bone resorption and increasing bone formation throughout at least three main pathways: (a) increasing osteoprotegerin and decreasing RANKL system; (b) decreasing cytokine levels; and (c) stimulating production of myokines and adipokines., Key Messages: Future research needs to be defined to develop evidence-based exercise guidance to provide optimal benefit for CKD using exercise interventions as adjuvant therapy for CKD-related complications such as anaemia and CKD-MBD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)