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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.)

Competing Interests: There are no conflicts of interest.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable multifocal cystic disease encountered in clinical practice, and it is usually diagnosed in patients with family history by the evidence of markedly enlarged kidneys with multiple bilateral cysts at ultrasound (U.S.), computed tomography (CT) scan, or magnetic resonance imaging (MRI). In most cases, genetic testing is not required. Though ADPKD diagnosis is often straightforward, misdiagnosis is possible. Here we present a case of ADPKD misdiagnosis, followed by a review of the most important kidney heritable multifocal cystic diseases. Our case report demonstrates that ADPKD can be erroneously diagnosed when other kidney heritable multifocal cystic diseases occur without their distinguishing manifestations and when there is no genetic characterization among the relatives. A proper diagnosis of heritable diseases is crucial, as it allows an appropriate management of family members who carry disease allele, apart from patient management. Therefore, we suggest a careful differential diagnosis with possible molecular genetic analysis in presentations with familial cystic kidneys and suspicious clinical and radiological features.

The rise of antimicrobial resistant (AMR) bacteria is a global public health threat. AMR Achromobacter bacteria pose a challenging clinical problem, particularly for those with cystic fibrosis (CF) who are predisposed to chronic bacterial lung infections. Lytic bacteriophages (phages) offer a potential alternative to treat AMR infections, with the possible benefit that phage selection for resistance in target bacteria might coincide with reduced pathogenicity. The result is a genetic "trade-off," such as increased sensitivity to chemical antibiotics, and/or decreased virulence of surviving bacteria that are phage resistant. Here, we show that two newly discovered lytic phages against Achromobacter were associated with stabilization of respiratory status when deployed to treat a chronic pulmonary infection in a CF patient using inhaled (nebulized) phage therapy. The two phages demonstrate traits that could be generally useful in their development as therapeutics, especially the possibility that the phages can select for clinically useful trade-offs if bacteria evolve phage resistance following therapy. We discuss the limitations of the current study and suggest further work that should explore whether the phages could be generally useful in targeting pulmonary or other Achromobacter infections in CF patients., (Copyright ©2022, Yale Journal of Biology and Medicine.)

Simple renal cysts are a common finding during abdominal imaging assessment. The incidence increases with age and it is higher in male gender. Parapelvic cysts are a subset of simple cysts that arise within the renal parenchyma, adjacent to the renal sinus, characterized by being generally single, larger, and incompletely surrounded by renal parenchyma. Noteworthy, parapelvic cysts are a rare and understudied condition which, although considered clinically insignificant due to the absence of influence on renal function, still have a controversial aetiopathogenesis. On the other hand, urological management and differential diagnosis have been thoroughly investigated. The aim of our review is to provide an overall vision on this rare condition, usually misdiagnosed and underestimated, on the basis of more recent data. An accurate differential diagnosis of parapelvic cysts can lead to the identification of treatable conditions such as Fabry disease, autosomal dominant polycystic kidney disease, polycystic liver disease and tuberous sclerosis complex disease., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3-5 patients treated with RAAS inhibitors (RAASi). We searched for RCTs in MEDLINE (PubMed), EMBASE databases, and the Cochrane register. Fragility indexes (FIs) for every primary and secondary outcome were calculated according to Walsh et al., who first described this novel metric, suggesting 8 as the cut-off to consider a study robust. Spearman coefficient was calculated to correlate FI to p value and sample size of statistically significant primary and secondary outcomes. Twenty-two studies met the inclusion criteria, including 80,455 patients. Sample size considerably varied among the studies (median: 1693.5, range: 73-17,276). The median follow-up was 38 months (range 24-58). The overall median of both primary and secondary outcomes was 0 (range 0-117 and range 0-55, respectively). The median of FI for primary and secondary outcomes with a p value lower than 0.05 was 6 (range: 1-117) and 7.5 (range: 1-55), respectively. The medians of the FI for primary outcomes with a p value lower than 0.05 in CKD and no CKD patients were 5.5 (range 1-117) and 22 (range 1-80), respectively. Only a few RCTs have been shown to be robust. Our analysis underlined the need for further research with appropriate sample sizes and study design to explore the real potentialities of RAASi in the progression of CKD.

In order to fight the SARS-CoV-2 pandemic, mass-vaccination programs have been launched globally starting December 2020. The pace of COVID-19 vaccines development was impressive and although data from clinical trials and post-authorization studies showed acceptable safety profile, additional studies and long-term population-level surveillance are needed. A possible link between all type of vaccination and immunological diseases is perhaps one of the hottest topics in literature; correspondingly, there is growing concern over the small but growing number of case reports linking COVID-19 vaccines with the development of glomerular disease. Our group conducted a systematic review of such cases. Results showed that IgA nephropathy (IgAN) and Minimal Change Disease (MCD) are the most frequently associated glomerulopathies. Interestingly, IgAN cases are mostly flares occurring few hours after the second dose of RNA vaccines and have a good clinical outcome, while both de novo and recurring MCD can occur up to 28 days after the first or second dose of vaccines. RNA vaccines are the most common vaccine type to be associated with glomerulopathy. Of course, this may simply reflect the more widespread use of these vaccines. However, compared to traditional vaccines, they do seem produce a higher antibody response and a stronger CD8+ T- and CD4+ T-cell response, including higher production of chemokines and cytokines., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder with an estimated prevalence between 1 : 1,000 and 1 : 2,500. Until a few decades ago, ADPKD was considered an untreatable disease, relentlessly progressing towards end-stage renal disease because of the lack of specific interventions. In the last decade, some aberrant molecular pathways involved in ADPKD development have been identified, and controlled clinical trials have been conducted to investigate the potential role of active drugs on these pathophysiological mechanisms such somatostatin and tolvaptan. Somatostatin analogues have been shown to be effective not only in ADPKD, but also in polycystic liver disease (PLD) with beneficial effect on cardiac function and a better cost/benefit profile; the only somatostatin analogue currently available for clinical use is octreotide long-acting release (octreotide-LAR), and it is approved only in Italy. On the contrary, tolvaptan is authorized worldwide and has received more attention in the last years, even if its clinical use is widely limited by aquaresis tolerability. The aim of this review is to investigate the advantages and drawbacks of somatostatin analogues and tolvaptan in the treatment of ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies., (© 2021. Italian Society of Nephrology.)

Hyperkalemia is common in patients treated with renin-angiotensin-aldosterone system inhibitors (RAASis), and it represents the main cause of the large gap reported between guideline recommendations and real-world practice in chronic kidney disease (CKD). We conducted a CKD-population-based restrospective study to determine the prevalence of patients with CKD treated with RAASis, incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia. Among 809 patients with CKD analyzed, 556 (68.7%) were treated with RAASis, and RAASi prescription was greater in stages 2-4 of CKD. Hyperkalemia occurred in 9.2% of RAASi-treated patients, and the adjusted rate of hyperkalemia among patients with stage 4-5 CKD was 3-fold higher compared with patients with eGFR > 60 ml/min/1.73 m 2 . RAASi treatment was discontinued in 55.3% of the patients after hyperkalemia event (74.2% discontinued therapy, 3.2% received a reduced dose, and 22.6% reduced the number of RAASi drugs). This study shows that the incidence of hyperkalemia is frequently observed in patients with CKD patients with RAASis, and that rates increase with deteriorating levels of kidney function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia., 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., (Copyright © 2022 Riccio, Capuano, Buonanno, Andreucci, Provenzano, Amicone, Rizzo and Pisani.)

A clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was - 176 ml (95%CI, - 406, 54; p < 0.133). Heterogeneity was low (I 2 :0%, p < 0.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment., (© 2021. The Author(s).)

Background: Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients' quality of life. Moreover, regular infusions are time-consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate., Methods: In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment-naΪve), and explored factors predictive for the infusion rate increase tolerability., Results: Fifty-two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p < .01). More severely affected patients (male patients and those with lower enzyme activity) received longer infusions for higher risk of infusion-associated reactions (IARs). A significant correlation between anti-agalsidase antibodies and IARs was found., Conclusion: Our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18-66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p < 0.0001). The frequency of adverse effects under migalastat and ERT was comparable (28% for both drugs). In conclusion, switching from ERT to migalastat is valid, safe and well tolerated.

Background: Fabry disease (FD) is a rare X-linked genetic disorder of glycosphingolipid catabolism caused by mutations in the GLA gene. Its heterogeneous presentation, the paucity of specific early markers, and the absence of a genotype-phenotype correlation are associated with a delayed or missed diagnosis. The true prevalence of FD remains so far unknown., Methods: A systematic search of FD screening studies in dialysis patients published from January 1995 until January 2019 was performed to reanalyze the prevalence of GLA mutations in this population after assigning their correct phenotype., Results: Twenty five screening studies involving 39,621 dialysis patients were included. Of them, 116 [91 males (0.23%) and 25 females (0.06%)] were positive to the GLA sequencing analysis. 56 (48.2%) had benign variant, 52 (44.8%) a pathogenic GLA mutation (39 classic and 13 late onset mutations) and 8 (6.9%) a mutation of uncertain significance. The overall prevalence of GLA variants was 0.24% [CI 95%, 0.17-0.32] while the overall prevalence recalculated on basis of only pathogenetic mutations was 0.14% [CI 95%, 0.08-0.20]. This difference was significant (P = 0.048)., Conclusions: Although the real prevalence of classic FD is low, the screening in the high-risk renal population remains of primary interest as an early diagnosis is fundamental for a timely specific therapy; moreover, the identification of index cases could allow patients' relatives to be investigated and promptly treated.

Purpose: Anastomotic leakage is considered the commonest major complication after surgery for rectal cancer., Materials and Methods: Patients who underwent laparoscopic LAR or ULAR for rectal cancer were recruited. The primary outcome was the incidence of the AL during 30 days postoperative., Results: Fifty-nine consecutive patients were included in the study. Fifty-three patients underwent LAR with stapled colorectal anastomoses, while the remaining 6 patients underwent ULAR with hand-sewn coloanal anastomoses. The median duration of operation was 195 minutes (range; 120-315). The defunctioning ileostomy was created in 24 (7%) patients. Overall, there was no recorded mortality. Only 10 (17%) patients developed complications. There were only 4 patients who developed AL. Three patients had a subclinical AL as they had defunctioning ileostomy at the time of the initial procedure, the diagnosis was made by CT with rectal contrast. They were treated conservatively with transanal anastomotic drainage under endoscopic guidance. One patient had a clinically significant AL, demonstrated as a peritonitis. This patient required reoperation during which pelvic abscess was drained, resection of the previous anastomosis, and hartmann's colostomy was performed., Conclusion: Standardization of a definition, as well as, criteria for the diagnosis of AL, will help in comparison of the results and the surgical techniques in order to optimize the required care offered to rectal cancer patients. On expert hands, it is feasible to perform a laparoscopic sphincter-saving total mesorectal excision, additionally, it provides the advantages of a clear view of the deep pelvis and facilitates a precise sharp dissection., Key Words: Anastomosis, Anastomotic Leakage, Rectal cancer, Total mesorectal excision.

Progressive nephropathy is one of the main features of Fabry disease. Although some clinical signs of Fabry nephropathy are already present in childhood, patients are often diagnosed relatively late in the course of the disease due to the absence of specific clinical markers, while a timely diagnosis and the prompt start of enzyme replacement therapy may be beneficial in stabilizing renal function or slowing its decline. Proteinuria/albuminuria has been accepted as the most important marker for Fabry nephropathy; however, a large proportion of renal impairment occurs in nonalbuminuric state. Therefore, early biomarkers may be useful for early identification of kidney involvement. The aim of this article is to review the current available literature on all biomarkers of Fabry nephropathy, with a comprehensive and critical description of their utilization in early recognition of renal damage., (© 2019 S. Karger AG, Basel.)

Background: The use of direct antiviral agents (DAA) has radically modified the course of HCV hepatitis in renal patients. Aim of this study was to assess the effects of HCV eradication on quality of life (QOL) in renal transplant recipients (RTR), measured by CLDQ and SF-36., Methods: Sixteen RTR with well preserved GFR (mean: 60.3±19.3 ml/min) and chronic HCV infection with moderate liver stiffness (9.3±1.7 kPa) were given a sofosbuvir-based regimen for 12 weeks and had a 1 year follow-up., Results: At end of treatment (EOT) a complete viral clearance was observed in all the patients, with normalization of most laboratory data and a consistent reduction in liver stiffness. All these parameters remained stable after 1 year, as well as renal function and proteinuria. Questionnaire data showed consistent amelioration in different "emotional" domains at EOT, which persisted after 1 year and were associated with a globally improved QOL, although there was no change in most of the "physical" domains in both questionnaires. One patient under ribavirin developed an acute anemia and withdrew from the study, but no further adverse episode was observed throughout the study., Conclusions: Our data, while confirming the efficacy of oral DAA, show that HCV infection represents a heavy psychological burden in renal transplant recipients, greatly alleviated by viral eradication, which determines a significant improvement in QOL that represents an important outcome in management of all transplant recipients. This trial is registered with ISRCTN97560076.