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Introduction: High-flux hemodialysis membranes may modulate the cytokine storm of SARS-CoV-2, but their impact on chronic hemodialysis (CHD) patients is unknown. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers and clinical outcomes in CHD patients with SARS-CoV-2. Methods: A prospective, observational study on CHD patients with SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021. Pre- and postdialysis C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) were determined at each session. Patients who underwent on-line hemodiafiltration (OLHDF) with a PMMA dialyzer were compared with those treated with OLHDF with a ATA dialyzer. The primary endpoint was the differences in the reduction ratio per session (RR) of CRP, PCT, IL-6, and IL-6 RR >25%. Results: We consecutively enrolled 74 CHD patients with COVID-19, 48 were treated with ATA membrane, and 26 with PMMA. Median IL-6 RR was higher in the ATA group compared to PMMA (17.08%, IQR −9.0 to 40.0 vs. 2.95%, IQR −34.63 to 27.32). Median CRP RR was 7.77% (IQR 2.47–13.77) in the ATA group versus 4.8% (IQR −2.65 to 11.38) in the PMMA group (p = 0.0017). Median PCT-RR% was 77.38% (IQR 70.92–82.97) in ATA group versus 54.59% (IQR 42.62–63.16) in the PMMA group (p < 0.0001). A multiple logistic regression analysis with IL-6 RR >25% as the outcome including the membrane employed, pre-dialysis IL-6, CRP, PCT, and ferritin showed that ATA led to a higher probability to reach the outcome (OR 1.891, 95% CI 1.273–2.840, p = 0.0018) while higher CRP favors the risk of lower IL-6 RR values (OR 0.910, 95% CI 0.868–0.949, p ≤ 0.0001). Conclusions: In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile, regarding IL-6 RR, compared to PMMA.

Chronic hemodialysis patients are at high risk of severe COVID-19 disease and death related to the infection. Anti-spike monoclonal antibodies administration reduces risk of disease progression and hospitalization in high-risk subjects but no clear data on end-stage renal disease are available. We report 2 cases of Bamlanivimab/Etesevimab administration to two not hospitalized chronic hemodialysis patients with SARS-CoV2 infection. Since they are large molecules (human immunoglobulin G1) with molecular weight of 146,000 Da, administration was conducted during the second hour of the dialysis session with no adverse reaction. Conclusions: Intradialytic administration of Bamlanivimab/Etesevimab could be considered safe and may allow adequate clinical observation time without hospital-stay prolongation.

Background/Aim: Supra hemodiafiltration with reinfusion of the endogenous ultrafiltrate (Supra-HFR) is a dialysis technique used to improve uremic toxin removal in the range of the middle molecular weight molecules. Supra-HFR does not require the preparation and online infusion of high-purity dialysis water because it allows the production of an endogenous ultrafiltrate that undergoes detoxification through an adsorbing resin. Patients and Methods: We investigated the ability of Supra-HFR to remove fibroblast growth factor 23 (FGF23), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and transforming growth factor alpha (TGF-alpha) after a single session dialysis in nine patients affected by end stage renal disease (ESRD). The same patients underwent a single session of online hemodiafiltration (OL-HDF) to evaluate possible differences in FGF23 and IL-6 levels. Results: A significant reduction in FGF23 was observed with both Supra-HFR (p=0.001) and OL-HDF. As for TNF-alpha and TGF-alpha, which were measured using Supra-HFR only, their percentage values were significantly lower at the end of dialysis than at the start (p=0.0028 and p=0.03, respectively). This did not change with post-dialysis rebound. Supra-HFR was found to have no effect on IL-6 and IL-8. Interestingly, the removal rate for FGF23 and IL-6 was similar to that observed with OL-HDF. Conclusion: Supra-HFR was not superior to OL-HDF, with suboptimal convective volume in the removal of the molecules tested, especially FGF23, which is considered a large middle molecular weight uremic toxin.

Hemodialysis (HD) is known to trigger a chronic inflammatory status, affecting the innate and acquired immune response. This study was aimed at a comparative analysis of immune cell subsets, proliferation, and apoptosis in subjects receiving chronic HD treatment with respect to a healthy control. Regardless of the dialysis filter used, we observed a reshaping of the acquired immune component both with respect to healthy patients and between the various sessions of dialysis treatment, with an impairment of CD3 cells, along with an increase in CD4 and CD8 cell populations producing pro-inflammatory factors such as IL-17 and IFN-gamma. The population of B cells, monocytes and NK cells were not impaired by the dialysis procedure. These results confirmed the high impact of the HD treatment on the patient’s immune system, underlying the imbalance of T cell counterparts.

Oliguric acute kidney injury due to traumatic rhabdomyolysis can be potentially lethal if the proper medical therapy combined with extracorporeal detoxification is not performed. Different extracorporeal techniques are available to overcome this syndrome. Here, we report the first case of removal of myoglobin and successful recovery from acute kidney injury in an elderly septic patient using supra-hemodiafiltration with endogenous reinfusion technique (HFR-Supra) combined with the medical therapy.

BACKGROUND AND AIMS Arteriovenous fistula (AVF) must be the first choice where eligible and a prompt approach within 48–72 h should be performed in case of acute AVF failure in order to maintain the patency of the vascular access. Evaluation of the most appropriate de-clotting technique must be made considering the patient's comorbidity, AVF characteristics and absolute, relative and temporary contraindications to each kind of corrective intervention. The outcome is different between the multiple methods and nowadays mechanical thromboaspiration (MT) seems to be an innovative and promising approach. METHOD A total of 9 AVF of 9 chronic haemodialysis patients with acute AVF failure were treated with MT between January 2019 and January 2022 and were retrospectively evaluated. MT was carried out via Indigo catheter (Penumbra Inc.), an aspiration system intended for the removal of emboli and thrombi from vessels through venipuncture of AVF/AVG: the continuous aspiration helps distinguish clots from normal blood flow; in case of resistant clots, separators of many sizes can be used at the tip of the catheter to facilitate their fragmentation and aspiration. Adjunctive procedures such as balloon angioplasty (used at all sites), local fibrinolysis, heparin infusion, or stents placement were considered. Technical success was defined by clot removal from AVF or AVG. Clinical success was defined by the restoration of thrill and bruit together with AVF usability after the procedure. Vascular access survival defined as AVF/AVG usability at 3 and 6 months was assessed. RESULTS Average age was 71.2 years; dialysis vintage was 93.4 months. Medium follow-up was 13.1 months. All patients needed placement of a temporary central venous catheter (CVC) and dialysis before the MT. Technical success was achieved in 100% of the procedures, clinical success was achieved in 88.9% of the MT (despite the technical success, in 1/9 patients AVF could not be used due to a severe residual venous stenosis). None reported peri-/intraprocedural complications. In 2/9 MT there was no use of anticoagulation; in 5/9 patients, a single unfractionated heparin bolus was used (2500 UI) during the manoeuvre; in 2/9 patients, a single 2500 UI bolus plus continuous intravenous infusion of unfractionated heparin was administered combined with local thrombolysis with urokinase: both patients needed blood transfusions after the manoeuvre, one of them reporting severe haemorrhage from AVF. As adjunctive procedures, 9/9 patients underwent balloon angioplasty; one of them needed stent placement over the venous stenosis. CVC was removed less than 48 h from the procedure in 5/9 patients (55.6%), in 3/9 patients it was removed after 48 h, while 1/9 patients maintained the temporary vascular access due to the lack of clinical success after MT. Double-needle puncture occurred after a medium time of 3.5 days. AVF survival at 3 months and 6 months was 66.6% (6/9 patients), while 3/9 patients faced AVF failure (1/3 patients deceased 2 months after the procedure with a functioning AVF, in 1/3 patients a relapse of AVG thrombosis occurred 2 months after the procedure, 1/3 never reached clinical success due to severe residual venous stenosis). At the time of study design, 3/9 patients resulted to be deceased due to causes unrelated to the procedure. (1/3 due to complications of abdominal surgery, 1/3 due to sepsis, 1/3 due to subarachnoid haemorrhage). CONCLUSION MT is an innovative yet functional and safe procedure that allows declotting of the thrombosed AVF while reducing or avoiding anticoagulation and/or surgery.

BACKGROUND AND AIMS High flux haemodialysis membranes may modulate the cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their impact in chronic haemodialysis (CHD) patients is not assessed [1, 2]. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers in CHD patients with SARS-CoV-2. METHOD A prospective, observational study on CHD patients (age ≥18 years) affected by SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021 and dialysis was performed at S. Orsola University Hospital (Bologna, Italy) Dialysis Unit. Mechanical ventilation at diagnosis was exclusion criteria. Pre- and post-dialysis C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were determined at each session and corrected for haemoconcentration during the complete SARS-CoV-2 period. Patients who underwent online haemodiafiltration (OLHDF) with PMMA dialyzer (Filtryzer BG-U™, Toray, surface area 2.1 m2 cut-off 20 kDa, KUF 43 mL/h/mmHg) were compared with those who underwent OLHDF with ATA dialyzer (SolaceaTM Nipro, surface area 2.1 m2 cut-off 45 kDa, KUF 72 mL/h/mmHg). The primary endpoint was to assess the differences in the reduction ratio/session (RR) of CRP, PCT and IL-6. RESULTS A total of 74 patients were enrolled, 48 were treated with ATA and 26 were with PMMA (420 versus 191 dialysis sessions). The main results are shown in Table 1. Median IL-6RR% was higher for ATA [17.08%, interquartile range (IQR) −9.0 to 40.0 versus 2.95%, IQR −34.63 to 27.32]. CRP and PCT showed higher RR with ATA in comparison to PMMA. When IL-6RR > 25% was the dependent variable in the multiple logistic regression analysis only ATA showed a significant correlation [odds ratio (OR) 1.891, 95% confidence interval (95% CI) 1.273–2.840, P = .0018) while higher CRP favoured the risk of lower IL6RR (OR 0.9101, 95% CI 0.868–0.949, P CONCLUSION In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile than PMMA, in particular regarding IL-6 RR.

BACKGROUND AND AIMS The QTc interval is a marker of arrhythmic risk in dialysis patients, and its lengthening has been associated with an increased risk of sudden death [1]. This phenomenon could be due to the accumulation of uremic toxins and their rapid removal with dialysis causing an imbalance of electrolytes currents [2]. The aim of the study is to describe the kinetics of potassium (K+) and other electrolytes during and after dialysis with the goal of validate a mathematical model for predicting the respective kinetics [3]. The secondary endpoint is to identify a correlation between the kinetics of intra (Ki) and extracellular K+ (Ke) during and after dialysis and the QTc interval. METHOD A total of 6 anuric HD patients were enrolled in an interventional, exploratory, prospective study. Clinical and pharmacological factors favouring the onset of arrhythmias or influencing the total mass of K + were excluded. Ki and Ke, Ca2+ Na, blood gas analysis, glucose and urea every 30 min were assessed during a 4 h HFR Supra dialysis session, the subsequent 7 h and at the start of the following session after 48 h. A 12-lead ECG was performed with the same schedule, and a bioimpedance vector analysis (BIVA) was obtained at the start and the end of the dialysis and 1 and 7 h after dialysis. Dialysate electrolytes were Na 140 mEq/L, K 3 mEq/L, Ca2+ 1.5 mEq/L and HCO3– 30 mmol/L. A selective ion probe was used to measure K+; the Ki value was obtained by an indirect formula expressed in a previous study [4]. The model of K + kinetics includes the Na+/K+/ATPase-dependent pump, the passive diffusion of K + from the intracellular to the extracellular compartment, the diffusion of K + through the filter, the intradialytic volume variation, the K + and solute rebound after dialysis, and the role of plasma osmolality [3]. RESULTS The model showed a better correlation to the in vivo data during the HFR phase than the post-dialytic one regarding Ke, sodium, HCO3– and Ca2+. The wide variability recorded by Ki is significantly in contrast with the stability predicted by the model, and the entity of post-dialysis Ca2+ drop was greater than that predicted by the model. Kinetics prediction of urea had a precise fitting with in vivo data in every phase. In Table 1, the in vivo results of the 6 patients regarding Ke, Ki, Ki/Ke, Ca2+ and QTc during and after HFR are resumed. In Fig. 1, we see the data extrapolated from a patient (likewise the others), where the greatest waving of the QTc occurred in the first hour post HFR in parallel with fluctuations of Ki and Ki/Ke. CONCLUSION The mathematical model for the prediction of the kinetics of solutes has shown a good correspondence with the in vivo data of K+, sodium, urea, Ca2+ and HCO3– during HFR, although it still needs to be refined in the post-dialysis phase. The major discrepancies for Ki could be due to difficult analytical processing. As to the greater drop of Ca2+ compared with the predicted, it can be due to the role played by other Ca2+ compartments in addition to the intra and extracellular ones. Although during the intradialytic period we faced a shortening of the QTc interval with a significant reduction in Ke, greater Ki/Ke and an increase in Ca2+ the post-HFR period appeared to be the most critical period. This phase corresponded to the largest fluctuations in QTc values, Ki, Ki/Ke ratio, and to the rapid rebound of K + and the drop of Ca2+.

Background and Objectives: Chronic hemodialysis (CHD) patients are at increased risk of SARS-CoV-2 infection and the related complications and mortality of COVID-19 due to the high rate of comorbidities combined with advanced age. This observational study investigated the clinical manifestations of SARS-CoV-2 infection in CHD and the risk factors for patients′ death. Materials and Methods: The study included 26 CHD patients with SARS-CoV-2 pneumonia detected by positive RT-PCR on nasopharyngeal swabs and high-resolution computed tomography at hospital admission, aged 71 + 5.9 years, 14 of which (53.8%) were male, 20 (77%) under hemodiafiltration, and 6 (23%) on standard hemodialysis, with a median follow-up of 30 days. Results: Simple logistic regression analysis revealed that the factors associated with a higher risk of death were older age (OR: 1.133; 95%CI: 1.028–1.326, p = 0.0057), IL-6 levels at admission (OR: 1.014; 95%CI: 1.004–1.028, p = 0.0053), and C-reactive protein (OR: 1.424; 95%CI: 1.158–2.044, p < 0.0001). In the multiple logistic regression model, circulating IL-6 values at admission remained the only significant prognosticator of death. The ROC curve indicated the discriminatory cut-off value of 38.20 pg/mL of blood IL-6 for predicting death in chronic hemodialysis patients with SARS-CoV-2 pneumonia (sensitivity: 100%; specificity: 78%; AUC: 0.8750; p = 0.0027). Conclusions: This study identified a threshold of IL-6 levels at hospital admission for death risk in CHD patients with SARS-CoV-2 pneumonia. This might represent a valuable outcome predictor, feasibly better than other clinical, radiological, or laboratory parameters and preceding the IL-6 peak, which is unpredictable.

Preservation of a vascular access is crucial in the management of hemodialysis patients. In this regard, percutaneous transluminal angioplasty (PTA) is an effective tool if performed after an adequate understanding of preliminary fistulograms. The present case showed a chronic dysfunction of a radial-cephalic arteriovenous fistula (AVF) due to arterial occlusion and partially relieved by the spontaneous development of multiple small arteriovenous connections in the palmar region of the hand. This dense network had been so far able to ensure a sufficient retrograde blood flow for an effective hemodialytic performance. The angioplasty of the post-anastomotic stenotic segment of the radial artery was effective in restoring this neoformed AVF patency.

Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant.

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients’ outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient’s outcome.

Background and Aims Hyperoxaluria is a rare metabolic disorder chacterized by widespread calcium oxalate deposition, if plasmatic oxalate level (pOx) overcomes saturation threshold. It could be primary (PH), a recessive disease associated with mutation of the liver enzyme LDH, or secondary (SH), in 75% due to intestinal malabsorption. Urolithiasis could be the first complication, and renal involvement could progress until end-stage renal disease (ESRD). Mean pOx is higher in chronic dialysis patients than healthy individuals because of impaired renal clearance. Oxalate molecular weight (MW) is 88 Da and its clearance is that of low MW uremic toxins. Our aim is to assess an association between arteriovenous fistula (AVF) failures and Hyperoxaluria. Method In the period between 1/1/2004 and 12/31/2020, diagnosis of Hyperoxaluria was carried out in 6 patients out of 1530 chronic dialysis patients (0.39%). The median age of patients was 65.5 [26-72] years, the male/female ratio was 3:3 and the median dialysis vintage was 36 [1-181] months. Three patients come to nephrological referral at stage 5 of CKD while 1 patient came to Italy when chronic HD was already started. At that time pOx was not considered. In these 4 patients the presumptive diagnosis of ESRD was urolithiasis and diagnosis of Hyperoxaluria was carried out after the beginning of chronic dialysis, when pOx and genetic analysis were performed. In 1 case biopsy on the kidney graft and in 1 case kidney biopsy after nephrectomy were performed: oxalate deposition was detected. For 2/6 patients diagnosis was carried out after biopsy of native kidneys before starting dialysis. All patients started medical therapy for hyperoxaluria. Five out of 6 patients were eligible to HD, 1/6 to PD. AVF was judged the first choice vascular access. Results PH was diagnosed in 3/6 patients: mutations were detected on chromosome 2. Malabsorption secondary to short bowel syndrome and chronic pancreatitis could be assumed as causes of SH in 3 patients. Patient 1 underwent 2 combined liver-kidney transplantation: the first failed by arterial grafts thrombosis and the second by renal primary non-function but the liver was still functioning, he died on HD after 12 years. Patient 2 underwent liver and kidney transplantation and she is nowadays dialysis-free. The median pOx pre-dialysis and before diagnosis was 165 [98-259] umol/L (Table 1). Patients on chronic HD underwent median of 3 [2-5] AVF interventions. Nine AVFs were distal and 4 were proximal. The most frequent complication was AVF thrombosis despite ASA treatment: half of the cases showed secondary AVF non-function, the other half of AVFs failed to mature. Six tunneled cuffed permanent catheters (TCCs) as definitive vascular access were successfully placed in the 5 patients on chronic HD. Warfarin therapy was started to avoid TCCs thrombosis. The median survival of TCCs was 9.5 [3-48] months. All the patients had a history of deep venous thrombosis (DVT). Conclusion To our knowledge this is the first case series of multiple AVF failures in patients with hyperoxaluria. In our experience TCCs show longer survival then AVF in this group of patients, even if it could not be excluded the role of warfarin in favoring this result. Even though a link between hyperoxaluria and thrombosis is well established, the exact underlying mechanism is still uncleared. The role of PD as dialysis technique of “first choice” should be enhanced also when residual renal function is abolished. In ESRD patients with urolithiasis, diagnosis of Hyperoxaluria should be ruled out before AVF placement.

Background and Aims Several chronic medical conditions appear to increase the risk of severe COVID-19. Chronic kidney disease (CKD) patients have a high risk of symptomatic infection and severe respiratory symptoms because of chronic inflammation, uremic toxins accumulation, endothelial dysfunction and an impaired immune response. Even though the presence of one or more comorbidities increases the risk of mortality, information of the outcome of COVID-19 in CKD patients is not yet available. The aim of the study is to present the incidence and outcome of COVID-19 in patients referring to our Nephrology Unit considering CKD patients, dialysis patients and kidney transplant recipients. MO520 Table 1. Demographic, clinical and radiological features. Variables Total (n=52) Survivors (n=39) Nonsurvivors(n=13) Age, yr 67.2± 13.8 65± 14 72± 12 Woman 21 (39%) 17 (44.7%) 5 (13%) Comorbidity CV disease 41 (78.8%) 30 (79%) 11(84.6%) DM 22 (42%) 14 (36.8%) 8 (61.5%) Cancer 18 (31%) 12 (31.6%) 6(46.1%) BMI>30 7 (3%) 4(10.5%) 2(15.4%) Dialysis 31(59.5%) 24 (63.1) 6 (46%) Kidney transplantation 16 (30.7%) 11 (29%) 2 (15%) CKD IV-V stage 4 (7%) 2 (5.2%) 1 (7.7%) Onset of Symptoms fever 29 (79%) 22(58%) 7 (13%) cough 3(6%) 2 (5.2%) 1 (7.7%) dyspnea 8 (15.4%) 4 (10.5%) 4 (30.8%) Symptomless 8 (15.4%) 6 (15.8%) 2 (15.4%) Admission HRCT Bilateral peripheral ground-gass opacity 39(81.2%) 31 (79.5%) 8(88.8%) Unilateral opacity 6 (12.5%) 5(12.8%) 1 (11.1) No opacity 3 (6.2%) 3 (7.7%) 0 PaO2/FiO2 ratio 330 ± 102. 376 ±93 286 ±86 Method This study is prospective single centre carried out considering patients referring to the Nephrology Unit of St. Orsola University Hospital in Bologna with COVID 19 diagnosis from 15THMarch to 30THMay 2020. Results Our cohort included 52 patients admitted to our Nephrology Unit because of Sars Cov2 infection confirmed by positive reverse transcriptase polymerase chain reaction on nasopharyngeal swab. The mean age was 67.2 ± 13.8 years (range, 33-88 years). Demographic, clinical and radiological features in Table 1. Forty-eight patients (92.3%) underwent chest TC. The main findings were: several bilateral interstitial pneumonia (39 patients, 81.2%), monolateral peripheral ground-glass opacities (6 patients, 12.5%), no signs of pneumonia (3 patients, 6.2 %). Clinical course is highly variable: 18 patients (34.6 %) were asymptomatic, 23 patients (44 %) had a mild course requiring low flux oxygen therapy and 11 patients (21%) presented severe pneumonia and respiratory distress that requires ventilatory support in intensive care unit. Forty patients (70%) had hydroxychloroquine-azithromycin dual therapy, 3 patients (6%) had antiviral therapy in addiction. Sixteen patients (31%) with P/F

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (&gt, 500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA, SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.

Background CPFA is an extracorporeal treatment used in severe sepsis to remove circulating proinflammatory cytokines. Limited evidence exists on the effectiveness of bilirubin adsorption by the hydrophobic styrenic resin, the distinctive part of CPFA. The aim of this study is to validate CPFA effectiveness in liver detoxification. Methods In this prospective observational study, we enrolled patients with acute or acute-on-chronic liver failure (serum total bilirubin > 20 mg/dL or MELD Score > 20) hospitalized from June 2013 to November 2017. CPFA was performed using the Lynda (Bellco/MedTronic, Mirandola, Italy) or the Amplya (Bellco/MedTronic, Mirandola, Italy) machines. Anticoagulation was provided with unfractionated heparin or citrate. Bilirubin and bile acids reduction ratios per session (RRs) were the main parameters for hepatic detoxification. Results Twelve patients with acute (n = 3) or acute-on-chronic (n = 9) liver failure were enrolled. Alcohol was the main cause of liver disease. Thirty-one CPFA treatments of 6 h each were performed, 19 with heparin and 12 with citrate. RRs was 28.8% (range 2.2–40.5) for total bilirubin, 32.7% (range 8.3–48.9) for direct bilirubin, 29.5% (range 6.5–65.4) for indirect bilirubin and 28.9% (16.7- 59.7) for bile acids. One patient received liver transplantation and 8/9 were alive at 1 year of follow-up. Three patients (25%) died: 2 during hospitalization and 1 for a cardiac event at 4 months of follow up with restored liver function. Conclusions CPFA resulted to be effective in liver detoxification. Thus, it may be considered as a “bridge technique” both to the liver transplant and to the recovery of the basal liver function.

Background and Aims Survival of patients with Multiple Myeloma (MM), Light Chain Amyloidosis (LCA) and Monoclonal Gammopathies of renal significance (MGRS) on chronic renal replacement therapy (RRT) is poor. The gold standand treatment of plasma cell dyscrasias (PCD) is high-dose chemotherapy followed by Autologous Stem Cell Transplantation (ASCT) which can induce complete remission and longer survival than chemotherapy alone. Kidney transplantation (KT) after ASCT could represent an option for patients with PCD and End Stage Renal Disease (ESRD). There is no evidence about the time of follow up required from MM remission and KT. Method We present a case series of 5 patients who underwent KT after ASCT and remission of MM among 2,500 transplant recipients followed at the Nephrology Dialysis and Renal Transplantation Unit of S.Orsola University Hospital from 1967 untill now. As in case of recovery from solid cancers, the feasibility of KT after MM was considered when no signs of relapse were assessed. In our cohort 3 patients were affected by Light Chain Deposition Disease (LCDD), 1 patient presented Myeloma Cast Nephropathy (MCN) and one patient Light Chain Amyloidosis (LCA). They all required RRT and underwent KT after ASCT. Results Time between ASCT and KT ranged from 3 and 11 years and clinical outcome was very different. The mean follow up period ranged from 2 to 4 years. In the first case (LCDD) KT was performed 11 years after ASCT, the graft failure occurred 6 years later because of chronic allograft nephropathy requiring RRT. In the second case (LCDD) patient received KT 3 years after ASCT. He developed Bence-Jones proteinuria requiring specific therapy with Dexametasone and Bortezomib determining progressive graft failure. In the third case (LCDD) KT was performed 4 years after ASCT and the 4 year follow up is negative for relapse of MM or ESRD. The fourth patient presented MCN and received KT 8 years after ASCT. MCN relapsed 6 years later; it caused ESRD requiring RRT. In the last patient (LCA) KT was performed 4 years after ASCT. No recurrence occurred in a 2-year follow up. Conclusion MM is the most frequent malignancy in dialytic population; the need for KT in MM remains high. ASCT improves the quality of life and offers higher survival in patients with myeloma/MGRS/amyloidosis-related ESRD. Therefore the combination of chemotherapy/ASCT and KT is pivotal to pursue renal restoring. Since high risk of recurrence larger study are required to clarify the better follow up period after MM remission and KT.

Background: In hemodialysis patients, a tunneled-cuffed permanent catheter is mandatory when the arteriovenous fistula is not feasible. The major risks of the use of tunneled-cuffed permanent catheter are bloodstream infections. The aim of this study is to analyze bloodstream infections from tunneled-cuffed permanent catheter in hemodialysis patients. Methods: An observational prospective study was carried out and 79 hemodialysis patients with tunneled-cuffed permanent catheter were enrolled. Patients were divided into those with bloodstream infections from tunneled-cuffed permanent catheter and those without. Their clinical and laboratory characteristics were compared. An original tunneled-cuffed permanent catheter lock therapy sequence was carried out combined with systemic antibiotic therapy. In case of antibiotic resistance, the tunneled-cuffed permanent catheter was removed. Results: The patients affected by bloodstream infections from tunneled-cuffed permanent catheter were 16/79 (20.3%). The bloodstream infection from tunneled-cuffed permanent catheter’s incidence rate was 0.52 per 1000 catheter days. Twenty-three bloodstream infections from tunneled-cuffed permanent catheter were found in 16/79 patients who used tunneled-cuffed permanent catheter. Staphylococcus aureus was the cause of bloodstream infection from tunneled-cuffed permanent catheter in 35% of the cases and Staphylococcus epidermidis in 30% of the cases. Risk factors were infection located in other organs and the presence of peripheral obstructive arterial disease. Conclusion: The enrolled cohort showed a reduced bloodstream infection from tunneled-cuffed permanent catheter incidence rate in comparison with the reference value (1 per 1000 catheter days). To reduce the number of bloodstream infections from tunneled-cuffed permanent catheter, hand hygiene and asepsis management of the tunneled-cuffed permanent catheter during the connection to the extracorporeal circuit and an original tunneled-cuffed permanent catheter lock therapy sequence seem to be the most efficient measures. Infections of other organs and the presence of peripheral obstructive arterial disease are the most important risk factors for bloodstream infections from tunneled-cuffed permanent catheter.

Coupled plasma filtration and adsorption (CPFA) is a detoxification system that combines a plasma adsorption circuit and a continuous renal replacement therapy circuit. Its main application is for sepsis and septic shock with or without acute renal failure. Several recent studies have suggested that CPFA can reduce the mortality when the volume of plasma absorbed on the styrenic resin is at least >0.18 L/kg/day. At present, new applications for CPFA are under investigation, also in patients without significant kidney failure. We report here a successful case of CPFA use during acute liver failure, with a complete recovery of liver function in a patient after severe cholangitis and relapsing hemolytic anemia. The resin enabled the removal of bilirubin and protein-bound toxins, while the hemofilter removed the hydrophilic toxins such as ammonia and non-protein-bound toxins as free bilirubin. We also describe a second case of CPFA application during thyrotoxicosis to achieve free triiodothyronine (FT3) and free thyroxin (FT4) adsorptions. The CPFA efficacy seems to exceed that obtained by plasma exchange (PEX) as to FT3 and FT4 adsorptions. The resin allowed the adsorption of FT3 and FT4. The role of the hemofilter is to enhance the hemodynamic tolerance of the extracorporeal treatment and remove water-soluble toxins. The reduced duration of CPFA treatments, in case of normal renal function, is confirmed by the assessment of the resin cartridge saturation. Thus, multipurpose CPFA can play a role in the case of resistance to current medical therapy or as a bridge to liver transplantation or thyroidectomy.

Vascular access-related complications are still one of the leading causes of morbidity in hemodialysis patients. The aim of this study was to compare polytetrafluoroethylene (PTFE) grafts versus tunneled cuffed permanent catheters (TCCs) in terms of vascular access and patients' survival. An observational study was carried out with a 2-year follow-up. Eighty-seven chronic hemodialysis patients were enrolled: 31 with a PTFE graft as vascular access for hemodialysis versus 56 with a TCC. Patients' mean age was 63.8 ± 14.6 (grafts) versus 73.5 ± 11.3 years (TCCs), P = 0.001. Significantly more patients with TCC had atrial fibrillation than patients with grafts (30.3% versus 6.5%, P = 0.01). In an unadjusted Kaplan-Meier analysis, median TCC survival at 24 months was 5.4 months longer than that of PTFE grafts but not significantly (log-rank test = 1.3, P = ns). In a Cox regression analysis adjusted for age, gender, number of previous vascular accesses, diabetes, atrial fibrillation, smoking, and any complication, this lack of significant difference in survival of the vascular access between TCC and PTFE groups was confirmed and diabetes proved to be an independent risk factor for the survival of both vascular accesses considered (P = 0.02). In an unadjusted Kaplan-Meier analysis, a higher mortality was found in the TCC group than in the PTFE group at 24 months (log-rank test = 10.07, P < 0.01). The adjusted Cox regression analysis showed that patients with TCC had a 3.2 times higher risk of death than patients with PTFE grafts. When an arteriovenous fistula (AVF) is not possible, PTFE grafts can be considered the vascular access of second choice, whereas TCCs can be used when an AVF or PTFE graft are not feasible or as a bridge to AVF or PTFE graft creation.

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been implicated in vascular calcification pathogenesis. CKD-MBD results in alterations in the number and function of circulating endothelial progenitor cells (EPCs), physiological regulators of angiogenesis and vessel repair, commonly defined as proangiogenic progenitor cells (PACs) by the antigen pattern CD34+CD133+KDR+CD45– and putative EPCs by the pattern CD34+CD133−KDR+CD45–. These cells might acquire a calcifying phenotype in CKD-MBD, expressing mineralization biomarkers. We investigated the expression of vitamin D receptor (VDR) and osteocalcin (OC) on EPCs of healthy individuals and haemodialysis patients, and their possible associations with circulating biomarkers of inflammation and vascular calcification. Methods: We compared EPC counts, expressing VDR or OC, in 23 healthy subjects versus 53 haemodialysis patients, 17 of them without vitamin D receptor agonist (VDRA) therapy and 35 treated with calcitriol (n = 17) or paricalcitol (n = 18). The correlations with serum levels of inflammatory and calcification indexes were also analysed. Results: All subsets expressing VDR or OC were significantly higher in haemodialysis patients compared with healthy controls, but PACs were increased only in VDRA treatment subgroup, while putative EPCs showed a similar rise also in untreated patients. In VDRA-untreated patients, OC+ PACs correlated positively with calcium levels, while in VDRA-treated patients, VDR+ PACs correlated positively with interleukin 6 levels, and OC+ PACs correlated positively 25-hydroxyvitamin D levels. Conclusions: Our data suggest that in CKD-MBD, EPCs undergo an endothelial-to-procalcific shift, representing a risk factor for vascular calcification. A link between mineral disorders and vitamin D replacement therapy emerged, with potential adverse effects for CKD patients.

INTRODUCTION AND AIMS: CPFA (Coupled plasma filtration and adsorption) is currently used in the treatment of severe sepsis with the intention of removing the proinflammatory mediators from the systemic circulation. Some evidence exist about the bilirubin adsorbing ability of the neutral styrenic resin which is part of the extracorporeal circuit of CPFA. The aim of this study is to assess efficacy and safety of CPFA in extracorporeal detoxification of liver toxins in patients affected by acute or acute-onchronic liver failure (Figure 1). METHODS: Twelve patients (age 23 - 73 years) with acute (n ¼ 3) or acute-on-chronic (n ¼ 9) liver failure were enrolled. A total of 31 CPFA treatments were carried out. Each CPFA treatment lasted 6 hours. Unfractionated heparin was used as anticoagulation of the extracorporeal circuit in 19 CPFA sessions; citrate anticoagulation with the concomitant infusion of calcium chloride in 12 CPFA sessions. The number of treatment for each patient was established on his/her clinical status. The reduction ratios per session of bilirubin and bile acids were considered. Hemoglobin, platelets, white blood cells, coagulation tests, urea, creatinine and electrolytes were also checked on starting CPFA and at the end of CPFA, as biocompatibility measures. RESULTS: All sessions were well tolerated by the patients. Alcohol was the most common etiology of the liver injury (n ¼ 9), 1 patient was affected by acute cholangitis and Fisher-Evans syndrome, 1 had a viral etiology, and 1 patient had a postoperative jaundice. Median reduction rate per session for total bilirubin was 28.8% (range 2.2 - 40.5); for direct bilirubin was 32.7 (range 8.3 - 48.9); for indirect bilirubin was 29.5% (range 6.5 - 65.4); for bile acids was 28.9% (16.7 - 59.7); for lactic acid was 30% (range -57.2%- 55.6%). In 10 out of 12 patients was observed a recovery of liver function. At one year of follow-up 2 patients died during the hospitalization; 6 patients are followed like outpatients, recovered their basal liver function and 1 of them is no more in the waiting list for the transplant. As to the remaining 4 patients who have not yet completed the one year follow-up, 2 out of 4 are still alive after a 6-month follow-up and recovered their basal liver function, 1 patient underwent a successful liver transplantation, the last patient is still alive after a 3-month follow up. CONCLUSIONS: Although CPFA is a non-standardized technique for the liver failure, its use in patients with acute or acute-on-chronic liver failure has shown favorable effects on safety and efficacy in terms of detoxification. Thus it is considerable a “bridge technique” toward the liver transplant and the recovery of basal liver function.