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Introduction. We have recently developed a new miniaturized device for extracorporeal ultrafiltration to be used in patients with fluid overload: Artificial Diuresis-1, or AD1 (Medica S.p.A., Medolla, Italy). The device has a reduced priming volume and operates at very low pressure and flow regimes and is designed to perform extracorporeal UF at bedside. After accurate experiments carried out in vitro, we report in this paper the results of in vivo tests ultrafiltration session carried out in selected animals according to veterinary best practice. Materials and methods. The AD1 kit is pre-filled with sterile isotonic solution and operates with a polysulfone mini-filter MediSulfone (Polysulfone at 50000 Dalton). A collection bag with a volumetric scale is connected to the UF line and the ultrafiltrate is obtained by gravity based on the height at which the ultrafiltrate collection bag is placed. Animals were prepared and anesthetized. Jugular vein was cannulated with a double lumen catheter. Three six hours sessions of ultrafiltration were scheduled with a target fluid removal of 1500 ml. Heparin was used as anticoagulant. Results. In all treatments the target value of ultrafiltration was obtained in the absence of major clinical or technical problems with a maximum deviation from the scheduled ultrafiltration rate lower than 10%. The device resulted safe, reliable, accurate and easily usable thanks to a user friendly interface and the very small dimensions. Conclusions. This study opens the way for clinical trials in different settings including departments with low intensity of care and even in ambulatory centers or patient’s home.

Introduction. Fluid overload has been associated with untoward outcomes in a variety of clinical settings. Isolated extracorporeal ultrafiltration (UF) allows for mechanical extraction of excess fluid and optimization of volume status without the established risks associated with use of high dose diuretics. Conventional machines for renal replacement therapy can be used to perform isolated UF. However, they typically need high blood flow rates with high circuit volumes and the therapy has to be performed by trained nurses. Herein, we describe a novel device, the Artificial Diuresis-1, or AD 1 (Medica S.p.A., Medolla, Italy), which is a portable technology designed to perform extracorporeal UF at bedside. Materials and Methods. The AD 1 uses a polysulfone mini-filter to generate ultrafiltrate with the help of two forces: blood flow (Qb) and gravity (based on the height at which the ultrafiltrate collection bag is placed). In vitro experiments were performed using human blood to evaluate vascular access pressures and ultrafiltrate volumes using various central venous catheters (12 Fr bilume, 10 Fr with 2 separate lumens, pediatric catheter 7 Fr). A variety of combinations were tested with Qb of 20, 35, 50 mL/min and collection bag height at 20, 40, 60 cm, measuring the UF rate per minute each while monitoring the pressures in the venous and arterial lines and filtration fraction. Results. The device’s performance was as expected. Regarding the pediatric CVC, it was possible to perform measurements only with a Qb of 20 mL/min due to increased venous pressure. Ultrafiltration rates when lines were directly connected to the blood container as well as for CVC Tesio ranged from 3.7 to 11 mL/min, for the CVC Niagara™ from 4.5 to 12.5 mL/min and for the CVC 7 Fr from 8.5 to 10 mL/min. The pressures of the vascular accesses were kept within a range of -5/-40 mmHg for the artery and +10/+70 mmHg for the vein. The highest venous pressure values were found with the CVC 7 Fr (+80/+100 mmHg). Conclusions. This novel device allows to treat patients with fluid overload in a variety of settings, from low-intensity department such as long-term care facilities to the intensive care unit. The device is small and portable, has a simple design, and is user-friendly. Future studies will be needed to evaluate whether gentle ultrafiltration and treatment of volume overload will translate into improvement in clinical outcomes such as a reduction in congestion-related hospital admission.

Background: Stenosis is the main cause of arteriovenous fistula failure and is due to neointimal hyperplasia. Percutaneous transluminal angioplasty is the gold standard for patients with vascular access stenosis. The aim of the study was to evaluate the efficacy and safety of ultrasound-guided percutaneous transluminal angioplasty in the treatment of native arteriovenous fistula venous stenosis. Methods: The need for intervention was determined by physical examination and duplex ultrasound in 162 patients. All patients with failing or not maturing arteriovenous fistula were treated in the outpatient setting under ultrasound guidance. Procedural success was assessed with repeated post-procedural ultrasound examinations. All procedures were performed under local anesthesia by a single nephrologist and were performed in a single vascular laboratory, while follow-up ultrasound was performed in the dialysis unit of destination. Results: Early technical success was obtained in 95.6% of cases (154 of 162). Complications occurred in 22 patients (13.5%) with no major complication requiring surgical or fluoroscopic endovascular intervention. Primary patency at 6 and 12 months was 84% and 69.8%, respectively. Risk factors for arteriovenous fistula failure/secondary percutaneous transluminal angioplasty were vascular access low blood flow rate and vintage, as well as the need for thrombolysis during the first percutaneous transluminal angioplasty. Conclusion: Ultrasound-guided percutaneous transluminal angioplasty is a valuable tool to treat vascular access stenosis.

Objectives Obesity is an important risk factor for morbidity and mortality. Vitamin K2 is involved in the production of bone and matrix amino acid g-carboxy-glutamic acid (Gla) proteins (vitamin K-dependent proteins [VKDPs]), regulating bone and vascular calcification (VC). Bone Gla protein (BGP) is involved both in bone mineralization and VCs. We assessed the relationships between vitamin K levels and body mass index (BMI) according to the hypothesis that the impact of BMI on mortality is partly driven by low vitamin K levels. Methods The Vitamin K Italian (VIKI) study included 387 hemodialysis patients from 18 dialysis centers in Italy. We determined plasma levels of bone markers: vitamin K levels, VKDPs, vitamin 25(OH)D, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and routine biochemistry. BMI was classified into the following categories: underweight (BMI 2), normal weight (18.5 ≤ BMI 2), overweight (25 ≤ BMI 2) and obese (BMI ≥ 30 kg/m2). Results 45.2% of patients were overweight or obese. Stratification by BMI demonstrated lower median menaquinone-7 (MK7)/triglycerides levels in obese patients (0.42 ng/mg [0.19, 0.87], p = 0.005). BGP levels were lower in overweight and obese patients (152 mcg/L [83.2, 251] and 104 mcg/L [62.7, 230], p = Conclusions These data are the first to report an inverse relationship between Vitamin K2 levels and BMI in hemodialysis patients. Further studies are needed to confirm these findings and to determine if lower levels of Vitamin K are related to greater morbidity and mortality in this at-risk population.

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

The frequent coexistence in daily clinical practice of chronic kidney disease (CKD) and atrial fibrillation (AF), especially in the elderly, represents a conundrum for physicians, mainly related to the management of anticoagulant therapy. The reduction of estimated glomerular filtration rate (eGFR) impairs anticoagulant clearance, increasing bleeding propensity. Moreover, dysfunctional responses of endothelial cells and inflammatory systems both trigger thromboembolic status. Those mechanisms pose an increased risk of adverse events for AF patients with CKD. While several data suggested the use of direct oral anticoagulants (DOACs) over warfarin as preferred anticoagulant strategy in patients with Stage 3A to Stage 4 CKD (eGFR range of 15–49 mL/min/1.73 m2), less is known about the optimal anticoagulation management in patients with end-stage renal disease (ESRD) or on renal replacement therapy (RRT). Furthermore, a pivotal feature to be considered when choosing the anticoagulant drug in CKD patients is represented by nephroprotective capability. Indeed, anticoagulant therapy with warfarin showed detrimental effects on kidney function, whereas DOACs demonstrated a beneficial effect on renal function preservation. Mounting data showed that, when pharmacological treatment cannot be pursued due to contraindication to anticoagulation, left atrial appendage occlusion (LAAO) may represent a valid alternative. This brief review outlines the current knowledge regarding anticoagulation therapy in ESRD/RRT patients, reporting new lines of evidence on the nephroprotective effect of oral anticoagulants and on the use of LAAO as a non-pharmacological alternative to oral anticoagulation.

COVID-19 mainly affects the respiratory system but has been correlated with cardiovascular manifestations such as myocarditis, heart failure, acute coronary syndromes, and arrhythmias. Cardiac arrhythmias are the second most frequent complication affecting about 30% of patients. Several mechanisms may lead to an increased risk of cardiac arrhythmias during COVID-19 infection, ranging from direct myocardial damage to extracardiac involvement. The aim of this review is to describe the role of COVID-19 in the pathogenesis of cardiac arrhythmias and provide a comprehensive guidance for their monitoring and management.

The burden of cardiovascular comorbid conditions was significantly higher in patients with atrial fibrillation (AF); most of them are affected by hypertension, chronic kidney disease (CKD) and/or diabetes mellitus (DM). DM represents a well-known risk factor for the development and maintenance of AF; the coexistence of DM and AF is also associated with an increased risk of mortality and stroke. Moreover, DM is currently the main cause of renal impairment and the leading cause of dialysis in the world. The hyperglycemia is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease. Long-term thromboembolic preventive therapy in AF patients with DM and CKD may be more challenging because both DM and CKD have been independently associated with an increased thromboembolic and bleeding risk, which results from the prothrombotic and proinflammatory status. Vitamin K antagonists (VKAs) are characterized by numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. On the other hand, Direct Oral Anticoagulants (DOACs) are currently contraindicated in dialysis patients even if mounting evidence suggests that they may have a nephroprotective role in AF patients with DM and CKD. Consequently, the choice of anticoagulant therapy in this setting of patient seems to be very challenging. The aim of this review is to investigate the role of DOACs in diabetic patients and its nephroprotective role by reviewing the current literature.

Atrial fibrillation (AF) is highly prevalent among patients with chronic kidney disease (CKD), and also associated with unfavorable outcome. Anticoagulant therapy is the mainstep of management in such patients, aimed at reducing the high risk of systemic thromboembolism and especially of ischemic stroke, which is reportedly associated with increased mortality in CKD patients. Even though new direct oral anticoagulant agents (DOACs) proved to be effective in patients with non valvular chronic AF, and are therefore recommended by recent guidelines for their treatment, warfarin is currently used in more than one-half of subjects needing oral anticoagulation, and only 30% of them are converted from a vitamin K antagonist- to a DOAC-based regimen. The main reason for not prescribing DOACs is often a reduction in renal function, even if mild. Aim of this review was therefore to evaluate the impact of DOAC therapy in the setting of CKD, from a nephrological perspective, by comparing available evidence on the role of DOACs in patients with CKD and AF with that emerging from traditional warfarin-based therapy. Both the pathogenesis of AF in CKD, and available findings of renal, cardiovascular and bone effects of DOACs in CKD are discussed, leading to the conclusion that DOAC therapy should be considered as the first line therapy for non valvular AF in patients with mild and moderate reduction of renal function, and could also be adopted for patients with severe CKD not on hemodialysis treatment, whereas there is insufficient evidence for ESRD patients on dialysis.

Background: The availability of direct oral anticoagulants (DOAC) in clinical practice has transformed the health care provided to patients for the prevention and treatment of thromboembolism. Safety and efficacy data guide clinicians in the choice of the drug used. To date, no evidence is available from head-to-head trials comparing different DOAC with regard to safety and efficacy; information is mainly derived from several meta-analyses and real-life studies. Conclusions from these studies are inconsistent and unsatisfactory. The evaluation of self-reported adverse drug reactions (ADR) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision-making. Objective: To analyze potential suspected ADR of DOAC using a previously described risk index (RI) in daily clinical practice in Italy. Methods: The National Pharmacovigilance Network database (from the AIFA website) was searched in order to retrieve information on all ADR related to oral anticoagulants occurring from 2013 to 2018. The ADR RI for each drug was calculated, where an RI = 1 indicates a balance between the percentage of ADR share and the percentage of market share for each DOAC; and an RI Results: The results showed that rivaroxaban is the DOAC with the lowest RI among the 4 molecules available today in Italy. Conclusions: Based on the RI, we identified rivaroxaban as the DOAC having the best safety profile.

The efficacy of antiplatelet treatment with aspirin in the primary prevention of major cardiovascular events was questioned during 2018, following a new series of trials that we summarize here in a quick synoptic overview. The three studies involved are the ASPREE trial, the ASCEND study and the ARRIVE trial. These studies all have a double-blind randomized design, and 100 mg/day aspirin was administered with an intention-to-treat approach and against placebo. Age of the enrolled patients, prevalence of diabetes mellitus and geographical location of other studies are just some of the elements analyzed here, in addition to the different problems of cardiovascular events. The ASPREE study observed a marginal reduction of cardiovascular events with the use of aspirin, by approximately 5% with a confidence interval at risk of insignificancy. On the other hand, the increased risk of a hemorrhagic event appeared to be rather robust, resulting between 18% and 62%. The ASCEND study observed a reduction in cardiovascular events of around 12%, offset by an increase in the risk of major bleeding between 9% and 52%. The ARRIVE study did not detect any incidence of major cardiovascular events, while the risk of major bleeding appeared to even double. The evidences of the current literature push us to review a widespread conviction among professionals who fight the war against cardiovascular disease every day: the prescription of aspirin in the primary prevention can no longer happen systematically, and every single prescription need care between benefits and dangers connected to the treatment.

Background and Aims It is estimated that Chronic Kidney Disease (CKD) accounts for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Although traditional CV risk factors are prevalent, other non-traditional CV risk factors such as vascular calcification (VC) are believed to contribute to this disproportionate CV risk burden in CKD subjects. We sought to investigate the association of Coronary Artery Calcification (CAC) progression with all-cause mortality in a cohort of patients new to hemodialysis (HD). Method This is a post hoc analysis of the Independent study (NCT00710788) originally designed to test the impact of 2 different phosphate binder regimens on various hard as well as surrogate endpoint in HD subjects. A total of 412 (88.4% of the Independent study cohort) underwent repeated CAC quantification according to the Agatston methods at study inception as well as after 12 months of follow-up. The square root method was used to assess CAC progression (CACP) and survival analyses were used to check the association of CACP and all-cause mortality. Results 412 middle age (65 years) men and women (51.2%) were considered. Detectable CAC was present in about 2 out 3 patients (68.2%) at study inception. At 12 months of follow-up completion, about 1 out of 3 subjects (33.1%) experience a significant CACP. CACP was associated with older age and use of calcium-based phosphate binders. At study completion (median follow-up: 36 months) 106 patients expired of all-cause. Age, diabetes mellitus, atherosclerotic CV events, baseline CAC extension were predictors of unfavorable outcome. Multivariable adjusted analysis confirmed an independent association of both baseline CAC (Hazard Ratio 1.29; 95% Confidence Interval: 1.17-1.44) and CACP (HR: 5.16; 95%CI: 2.61-10.21) with all-cause mortality. However, CACP diminished the risk associated with baseline CAC (p for interaction term 0.002) and use of calcium-free phosphate binders significantly weakened the link between CACP (HR. 1.95; 95%CI: 0.92-4.16) and mortality Conclusion Baseline CAC as well as CACP predict mortality in incident to HD individuals. Nevertheless, CACP mitigates the risk associated with baseline CAC and calcium-free phosphate binders attenuates the association of CACP and mortality, suggesting that CACP modulation may impact survival in this population

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K+) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin–angiotensin–aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K+ homeostasis, and we review the effects of dietary K+ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K+ secretion in response to an exogenous load, particularly in the context of “occult” CKD, HF, and in patients taking RAASis and/or MRAs.