Citrate pharmacokinetics and calcium levels during high-flux dialysis with regional citrate anticoagulation

Background. Regional citrate anticoagulation is a very effective anticoagulation method for haemodialysis. However, it is not widely used, primarily due to the risk of hypocalcaemia. We studied citrate and calcium kinetics to better understand safety aspects of this anticoagulation method

Efficacy of lipid reduction with DALI and MONET

Background: Lipidapheresis techniques are increasingly used to treat drug-resistant hyperlipidemia but few efficacy studies under routine application are available. In this multicenter observational study we investigated direct adsorption of lipoproteins (DALI) and lipoprotein filtration (MONET) for the short and the long-term effects on lipid-lowering effects. Methods: Data of 122 apheresis patients from 11 centers (DALI: n = 78, MONET: n = 44) were prospectively collected for a period of 2 years. Routine lipid measurements were evaluated (2154 DALI and 1297 MONET sessions). It was investigated whether the relative reduction of LDL-C during apheresis session achieves at least 60%. Also relative reduction of total cholesterol, HDL, triglyceride, and Lp(a) were analyzed. Results: The relative reduction of LDL-C was at least 60%: DALI: 70.62%, 95% CI = [69.34; 71.90] and MONET: 64.12%, 95% CI = [60.79; 67.46]. Also triglycerides were reduced with both systems: DALI 38.63%, 95% CI = [33.95; 43.30] vs. MONET 57.68%, 95% CI = [51.91; 63.45]. Relative reductions of total cholesterol were in the range of 50% (DALI 95% CI = [46.49; 49.65] MONET 95% CI = [48.93; 55.26]) and of Lp(a) in the range of 65% (DALI 95% CI = [61.92; 65.83] MONET 95% CI = [63.71; 70.30]. HDL reduction was: DALI 15.01%, 95% CI = [13.22; 16.79] and MONET 22.59%, 95% CI = [19.33; 25.84]. For both devices treated patient plasma/blood volume and in case of DALI the use of the larger adsorber configurations (DALI 1000 and DALI 1250) were independent positive predictors of the relative reduction of LDL-C and of Lp(a). Conclusions: Both systems effectively improved lipid profile and reduced atherogenic lipids. The results point to the importance of the individualized application of these valuable therapies to achieve clinical targets. (C) 2017 Published by Elsevier Ireland Ltd

Safety aspects of lipidapheresis using DALI and MONET – Multicenter observational study

Background: Lipidapheresis was introduced for intractable hyperlipidemia as a more selective therapy than plasma exchange aiming to enhance efficacy and limit side-effects. Although this therapy is regarded safe, multicenter data from routine application are limited. We investigated direct adsorption of lipoproteins (DALI) and lipofiltration (MONET) regarding the short and the long-term safety aspects. Methods: This multicenter observational study prospectively evaluated 2154 DALI and 1297 MONET sessions of 122 patients during a period of 2 years. Safety parameters included clinical side-effects (adverse device effects, ADEs), technical complications, blood pressure and pulse rate. Also routinely performed laboratory parameters were documented. Analysis of laboratory parameters was not corrected for blood dilution. Results: Overall 0.4% DALI and 0.5% MONET treatments were affected by ADE. Technical complications occurred in 2.1% and in 0.8% DALI and MONET sessions, respectively. The most frequent ADE was hypotension, and the majority of technical problems were related to vascular access. Both types of treatments led to a drop of thrombocytes in the range of 7-8%. Hematocrit and erythrocytes decreased only during the DALI treatments by about 6%. Leucocytes decreased during the DALI therapy (similar to 15%), whereas they increased during the MONET application (similar to 11%). MONET treatment was associated with a higher reduction of proteins (fibrinogen: 58% vs. 23%, albumin: 12% vs. 7%, CRP: 33% vs. 19% for MONET and DALI, respectively). Apart from severe thrombocytopenia in two DALI patients, changes of other parameters were typically transient. Conclusions: Under routine use the frequency of side-effects was low. Still, monitoring of blood count and proteins in chronic apheresis patients is recommended. (C) 2017 Published by Elsevier Ireland Ltd

Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure

BACKGROUND & AIMS: Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. METHODS: Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. RESULTS: Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. CONCLUSIONS: Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients

EBioMedicine / Extracorporeal IgE Immunoadsorption in Allergic Asthma: Safety and Efficacy

Background Prevention of IgE-binding to cellular IgE-receptors by anti-IgE (Omalizumab) is clinically effective in allergic asthma, but limited by IgE threshold-levels. To overcome this limitation, we developed a single-use IgE immunoadsorber column (IgEnio). IgEnio is based on a recombinant, IgE-specific antibody fragment and can be used for the specific extracorporeal desorption of IgE. Objective To study safety and efficacy of IgEnio regarding the selective depletion of IgE in a randomized, open-label, controlled pilot trial in patients with allergic asthma and to investigate if IgEnio can bind IgE-Omalizumab immune complexes. Methods Fifteen subjects were enrolled and randomly assigned to the treatment group (n = 10) or to the control group (n = 5). Immunoadsorption was done by veno-venous approach, processing the twofold calculated plasma volume during each treatment. A minimum average IgE-depletion of 50% after the last cycle in the intention-to-treat population was defined as primary endpoint. Safety of the treatment was studied as secondary endpoint. In addition, possible changes in allergen-specific sensitivity were investigated, as well as clinical effects by peak flow measurement and symptom-recording. The depletion of IgE-Omalizumab immune complexes was studied in vitro. The study was registered at clinicaltrials.gov (NCT02096237) and conducted from December 2013 to July 2014. Results IgE immunoadsorption with IgEnio selectively depleted 86.2% (5.1% SD) of IgE until the end of the last cycle (p < 0.0001). Removal of pollen allergen-specific IgE was associated with a reduction of allergen-specific basophil-sensitivity and prevented increases of allergen-specific skin-sensitivity and clinical symptoms during pollen seasons. IgEnio also depleted IgE-Omalizumab immune complexes in vitro. The therapy under investigation was safe and well-tolerated. During a total of 81 aphereses, 2 severe adverse events (SAE) were recorded, one of which, an episode of acute dyspnea, possibly was related to the treatment and resolved after administration of antihistamines and corticosteroids. Conclusions This pilot study indicates that IgE immunoadsorption with IgEnio may be used to treat patients with pollen-induced allergic asthma. Furthermore, the treatment could render allergic patients with highly elevated IgE-levels eligible for the administration of Omalizumab and facilitate the desorption of IgE-Omalizumab complexes.(VLID)485282