Comparison of 2 medium cutoff dialyzers versus on-line hemodiafiltration regarding depurative ability and albumin loss: An uncontrolled clinical research.

BACKGROUND: Hemodialysis (HD) techniques that best remove molecules in the middle to high molecular weight range are on-line hemodiafiltration (OL-HDF) and HD with medium cut-off (MCO) membranes. The aim of this study was to compare efficacy and safety of OL-HDF with FxCordiax HDF 800™, with HD with 2 MCO dialyzers: Theranova 500® and the new Elisio 21HX™ dialyzer. METHODS: Fourteen patients following treatment with OL-HDF using FxCordiax HDF 800™ were randomized to receive a consecutive 1-week HD treatment with Theranova 500® and Elisio 21HX™.The reduction rate (RR) of differently sized molecules was compared, as well as the variation rate in molecules smaller than 1000, detected by nuclear magnetic resonance based chemometrics (metabolomics). Albumin loss in dialysate was quantified. RESULTS: Lower RRs were found for molecules around 20 000 with Elisio 21HX™ compared to OL- HDF (RR prolactin 58.5% versus 66.7%, p = 0.034; RR Kappa light chain 63.1% versus 71.8%, p = 0.010). Albumin loss per session was higher with Theranova 500® than with OL-HDF and with Elisio 21HX™ (2249.9 ± 714.1 mg, 815.2 ± 474.0 mg, 442.9 ± 135.9 mg, p < 0.001, respectively). Metabolomic studies suggested, by semi-quantitative analysis, a greater depurative capacity of OL-HDF, followed by Elisio 21HX™, and then Theranova 500®. CONCLUSIONS: In this study, HD with Theranova 500® has proven to be very similar in efficacy to OL-HDF, although with a significantly higher albumin loss. HD with Elisio 21HX™ resulted in lower removal of molecules around 20 000 compared to OL-HDF, with no significant difference compared to Theranova 500®, and with less albumin loss than Theranova 500®.

Chlorhexidine - a commonly used but often neglected culprit of dialysis associated anaphylactic reactions (case report).

BACKGROUND: Hemodialysis-associated anaphylactic reactions are rare and frequently complex in nature due to the sheer number of possible culprit agents. Unfortunately, dialysis is often unavoidable or strictly essential for life-saving solute clearance or fluid removal in patients with end stage kidney failure and those with severe acute kidney injury. It is of utmost importance that the culprit agent is identified and avoided to allow continuation of dialysis treatment as needed. CASE PRESENTATION: We present 2 cases of hemodialysis-associated anaphylactic reactions. These patients developed anaphylactic reactions peri-dialysis and were initially suspected to have dialyser reactions. They were investigated in a controlled healthcare setting and possible culprit agents were systemically identified and eliminated. They both underwent allergy testing and were diagnosed with chlorhexidine allergy. Of note, Case 1 was an incident dialysis patient at the time of presentation and Case 2 was a prevalent dialysis patient. This suggests that the time from initial sensitization to reaction may not always be helpful in determining if a particular agent is the culprit of an anaphylactic reaction. In both cases, the patients were dialysed through a tunnelled dialysis catheter. We postulate that the presence of an exit site, which represents a compromise to the integrity of the skin's epidermal barrier, may have a significant role in the development of these reactions. As chlorhexidine is a widely used disinfectant in hemodialysis, it is imperative that we consider it as a possible culprit agent when these reactions arise. To our knowledge, there are no other reported cases of anaphylaxis secondary to chlorhexidine use in dialysis patients other than a previous report in 2017. Our report also highlights the possibility of these reactions occurring more frequently in patients with damaged epidermal barriers and in patients exposed to higher environmental concentrations of chlorhexidine. These are novel concepts that can be explored with further research. CONCLUSION: Chlorhexidine associated anaphylactic reactions can occur in the peri-dialysis setting and a high index of suspicion is paramount to diagnosis.

Medium Cut-Off Membrane Can Be a New Treatment Tool in Amanita phalloides Poisoning.

Mushroom poisoning is a common health problem that can be seen seasonally and geographically. Most mushroom poisoning requiring treatment worldwide is due to Amanita phalloides. Although liver failure and kidney injury are frequent, poisoning can also lead to more serious clinical situations, such as shock, pancreatitis, encephalopathic coma, cardiac failure, disseminated intravascular coagulation, and multiple organ dysfunction syndrome, and may cause death. In addition, when standard treatment approaches fail, extracorporeal treatment methods are often used. We report 2 cases in which hemodialysis with medium cut-off membrane was performed. We observed an improvement in liver and kidney function in both of our cases. The first case recovered, but the second case proved fatal owing to Acinetobacter sepsis, despite an improvement in renal function. Medium cut-off membrane hemodialysis may be an alternative option in the treatment of Amanita phalloides poisoning.

Comparison of the removal of uraemic toxins with medium cut-off and high-flux dialysers: a randomized clinical trial.

BACKGROUND: Accumulation of middle-weight uraemic toxins in haemodialysis (HD) patients results in increased morbidity and mortality. Whether medium cut-off HD (MCO-HD) improves removal of middle-weight uraemic toxins remains to be demonstrated. METHODS: This cross-over prospective study included 40 patients randomly assigned to receive either 3 months of MCO-HD followed by 3 months of high-flux HD (HF-HD), or vice versa. The primary endpoint was myoglobin reduction ratio (RR) after 3 months of MCO-HD. Secondary endpoints were the effect of MCO-HD on other middle-weight toxins and protein-bound toxins, and on parameters of nutrition, inflammation, anaemia and oxidative stress. RESULTS: Compared with HF-HD, MCO-HD provided higher mean RR of myoglobin (36 ± 8 versus 57 ± 13%, P < 0.0001), beta2-microglobulin (68 ± 6 versus 73 ± 15%, P = 0.04), prolactin (32 ± 13 versus 59 ± 11%, P < 0.0001), fibroblast growth factor 23 (20 ± 21 versus 41 ± 22%, P = 0.0002), homocysteine (43 ± 7 versus 46 ± 9%, P = 0.03) and higher median RR of kappa [54 (48-58) versus 70 (63-74)%, P < 0.0001] and lambda free light chain (FLC) [15 (9-22) versus 44 (38-49)%, P < 0.0001]. Mean ± SD pre-dialysis levels of beta2-microglobulin (28.4 ± 5.6 versus 26.9 ± 5.1 mg/L, P = 0.01) and oxidized low-density lipoprote (6.9 ± 4.4 versus 5.5 ± 2.5 pg/mL, P = 0.04), and median (interquartile range) kappa FLC [145 (104-203) versus 129 (109-190) mg/L, P < 0.03] and lambda FLC [106 (77-132) versus 89 (62-125) mg/L, P = 0.002] were significantly lower. Mean albumin levels decreased significantly (38.2 ± 4.1 versus 36.9 ± 4.3 g/L, P = 0.004), without an effect on nutritional status as suggested by unchanged normalized protein catabolic rate and transthyretin level. CONCLUSIONS: Compared with HF-HD, MCO-HD provides higher myoglobin and other middle molecules RR and is associated with moderate hypoalbuminemia. The potential benefits of this strategy on long-term clinical outcomes deserve further evaluation.

Treatment of ibuprofen intoxication with charcoal haemoperfusion in two dogs.

Case history: Two dogs presented separately to the Small Animal Hospital, University of Florida (Gainsville, FL, USA) for ingestion of ibuprofen. The first dog ingested 561.8 mg/kg ibuprofen in addition to paracetamol and caffeine and vomited prior to admission. This patient also received fluid therapy for 8 hours prior to charcoal haemoperfusion. The second dog ingested 500 mg/kg of ibuprofen and the owners induced vomiting with hydrogen peroxide prior to presentation. Due to the severity of clinical signs, both patients were treated with charcoal haemoperfusion.Clinical findings: The concentrations of ibuprofen in the blood of the dogs prior to treatment were 478 and 301 mg/L. During the treatment ibuprofen concentrations were reduced by 95.8% and 45.5%, respectively, with no treatment side effects and minimal clinical signs after treatment.Diagnosis: Toxicity due to ingestion of ibuprofen toxicity that was successfully treated with charcoal haemoperfusion.Clinical relevance: In the cases described here minimal benefit was seen after 3 hours of treatment using one haemoperfusion cartridge. This is in contrast to a previously published report in which dogs were treated for 6 hours with two charcoal haemoperfusion cartridges. This suggests that one cartridge may be sufficient. The amount of ibuprofen ingested was not a reliable predictor of the concentration in blood at the initiation of treatment. Charcoal haemoperfusion is an effective means of reducing plasma concentrations of ibuprofen, however, its use may be limited by its cost and availability.

Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.

BACKGROUND: Removal of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population. METHODS: REMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and ß-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death. DISCUSSION: MCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482 . Date of registration - 21/06/2016.

Enhancing dialyser clearance-from target to development.

Products of metabolism accumulate in kidney failure and potentially have toxic effects. Traditionally these uraemic toxins are classified as small, middle-sized and protein-bound toxins, and clearance during dialysis is affected by diffusion, convection and adsorption. As current dialysis practice effectively clears small solutes, increasing evidence supports a toxic effect for middle-sized and protein-bound toxins. Therefore, newer approaches to standard dialysis practice are required to look beyond urea clearance. Current dialysers have been developed to effectively clear small solutes and secondly to increase middle-sized toxin clearances. However, there is no ideal dialyser which can effectively clear all uraemic toxins. Advances in nanotechnology have led to improvements in manufacturing, with the production of smoother membrane surfaces and uniformity of pore size. The introduction of haemodiafiltration has led to changes in dialyser design to improve convective clearances. Both diffusional and convectional clearances can be increased by changing dialyser designs to alter blood and dialysate flows, and novel dialyser designs using microfluidics offer more efficient solute clearances. Adjusting surface hydrophilicity and charge alter adsorptive properties, and greater clearance of protein-bound toxins can be achieved by adding carbon or other absorptive monoliths into the circuit or by developing composite dialyser membranes. Other strategies to increase protein-bound toxins clearances have centred on disrupting binding and so displacing toxins from proteins. Just as the hollow fibre design replaced the flat plate dialyser, we are now entering a new era of dialyser designs aimed to increase the spectrum of uraemic toxins which can be cleared by dialysis.

Effects of medium cut-off dialysis membranes on inflammation and oxidative stress in patients on maintenance hemodialysis.

PURPOSE: Medium cut-off membranes were developed for providing increased clearance of larger middle-molecule uremic toxins. We compared the effect of low-flux, medium cut-off, and high-flux membranes on chronic inflammation and oxidative stress in patients with maintenance hemodialysis. METHODS: A total of 42 patients were enrolled in this study. Total antioxidant status, total oxidant status, paraoxonase-1, ischemia-modified albumin, total Thiol, disulfide bond, and native Thiol were measured to determine oxidative stress. C-reactive protein was measured to define inflammation. RESULTS: 37% of the total patients were females, and the mean age was 52.9 ± 16 years. Serum albumin and Kt/V were similar between groups during the study period. We did not find any significant difference at baseline in the 3rd and 6th months of the study when we compared the inflammatory marker and oxidative indicator levels between three hemodialysis membranes in the whole study group. In the subgroup analysis of 19 patients with a high C-reactive protein level, we found that the medium cut-off membrane significantly reduced serum C-reactive protein level, when compared to low-flux and high-flux membrane [2.8 mg/L vs. 13.7 mg/L and 6.1 mg/L, respectively, p = 0.05]. However, we did not find a significant change in oxidative stress indicators in patients with high C-reactive protein levels between the three dialysers. CONCLUSION: The medium cut-off membrane has favorable effects on inflammation in patients with maintenance hemodialysis. However, this positive effect could not be demonstrated in oxidative stress.

Evaluation of the dialyser inner diameter in online haemodiafiltration. / Valoración del diámetro interno del dializador en hemodiafiltración on-line.

INTRODUCTION: Online haemodiafiltration (OL-HDF) has been associated with increased survival. To date, the influence of the inner diameter of the hollow fibres of the dialyser on convective volume has not been well established. The objective of the study was to evaluate the effect of increasing the inner diameter of the dialyser on the convective volume and removal capacity. MATERIAL AND METHODS: We included 16 patients in posdilutional OL-HDF with autosubstitution. Each patient was analysed in 4 sessions in which the inner diameter varied; 185µm (FX60 Cordiax and FX80 Cordiax) versus 210µm (FX600 Cordiax and FX800 Cordiax). Different solutes were measured at the beginning and end of each dialysis session. RESULTS: No differences in the convective volume were found with an increased inner diameter: 32.3±3.1 vs. 31.8±3.6 l/session (FX60 vs. FX600) and 33.7±4.3 vs. 33.5±3.8 l/session (FX80 vs. FX800). The reduction percentages also did not differ: urea 83.7±4.5 vs. 84.1±3.4 for FX60 and FX600, and 82.7±4.1 vs. 83.6±3.8 for FX80 vs. FX800; creatinine similar 78.2±5.6 vs. 77.8±4.6 y 77.1±5.4 vs. 78.1±4.9; ß2-microglobulin 82.2±4.3 vs. 82.9±4.2, and 82.9±4.7 vs. 84.0±3.8; myoglobin 71.0±10 vs. 70.2±9 and 72.8±11 vs. 75.0±10; prolactin 70.4±9 vs. 68.1±9, and 72.2±10 vs. 73.4±8.2; and α1-microglobulin 22.9±10 vs. 21.6±10, and 26.5±12 vs. 28.8±11, respectively. CONCLUSION: The increase in the inner diameter of the hollow fibres did not result in improved convective volume and removal capacity.