High-flux Hemodialysis Research Articles

Effects of High-Flux Hemodialysis on Inflammatory Factors and Nutritional Status in Patients with Severe Renal Failure

Objective: To investigate the effects of high-flux hemodialysis on inflammatory factors and nutritional status in patients with severe renal failure. Methods: A total of 72 patients with severe renal failure who underwent dialysis treatment in the hospital from January 2017 to March 2019 were selected as the research subjects, and they were randomly divided into 2 groups with 36 patients each. The control group underwent low-flux hemodialysis, and the observation group underwent high-flux hemodialysis. The levels of inflammatory factors and nutritional status were compared between the two groups after treatment. Results: The levels of various inflammatory factors in the observation group were lower than those in the control group and the nutritional indexes were higher than those in the control group after 4 weeks of treatment (P<0.05). Conclusion: High-throughput hemodialysis in patients with severe renal failure can significantly reduce the levels of inflammatory factors and improve nutritional status.

Expanded hemodialysis: new opportunities and hopes

In the field of hemodialysis technologies, as in other fields of medicine, evolutionary changes are constantly taking place. The innovations are driven by unachieved clinical outcomes and desire to improve the quality of care of patients with CKD 5D. Recent advances in dialysis techniques resulted in the possibility to expand the permeability of dialysis membranes for a wider spectrum of uremic toxins that lead to the enhancement of long-term outcomes improving quality of life and reducing the mortality rate of dialysis patients. The inadequacy of existent dialysis techniques, at least in part, is due to the chronic accumulation of organic retention solutes of middle and large molecules, which are poorly or even not removed during dialysis.
 A gradual improvement in the elimination of uremic toxins is observed as a result of the development of new alternative approaches of hemodialysis therapy, such as high-flux hemodialysis, hemodiafiltration, expanded hemodialysis (HDx). However, some techniques have had limited success due to a host number of organizational, technological, financial and human factors. Expanded hemodialysis offers a novel blood purification technology in removal of the large spectrum of uremic toxins, in particular large medium molecules, due to the new structure of the dialysis membrane. There are a number of studies that prove the potential benefits of a new method of dialysis therapy over the previous ones, suggesting a reduction in cardiovascular mortality, vascular calcification and inflammation. In addition, there is evidence of a positive effect of HDx on the quality of life in dialysis patients. In particular, to minimize the manifestations of skin itching, restless legs syndrome, asthenic syndrome.

Effect of hemodiafiltration on sclerostin level and bone specific alkaline phosphatase in comparison with high flux dialysis

Abstract Background sclerostin, an osteocyte-derived glycoprotein acts as a soluble inhibitor of the Wnt signaling pathway and its physiological role is to reduce bone formation. The serum sclerostin levels increase with the progression of CKD. Aim of the work in the present study, we investigated the effect of three months thrice weekly hemodiafiltration on serum sclerostin level and bone specific alkaline phosphatase in comparison with high flux dialysis in stable HD patients. Methods prospective study was concluded upon 32 randomly selected ESRD patients from Dialysis Department in Ain Shams University Hospitals and Maadi Military Hospital. Serum sclerostin and bone specific alkaline phosphatase were measured at the start of the study (Zero months) and after 3 months of HDF dialysis between September 2017 and December 2017. Results 32 test subjects were randomly selected had mean age 47.38 (± 18.68 years) in HDF group and 55.31 (± 7.40 years) in high flux group. 56.3% were male in HDF group, 81.3% male in high flux group. Patients in HDF group had serum sclerostin reduction ratio with mean 24.72 ± 10.34 pre-3 months and mean 30.34 ± 12.22 in post-3 months. While, serum sclerostin reduction ratio mean was 18.97 ± 7.87 in high flux group. There was a statistically significant difference between HDF group post-3months and high flux group as regard sclerostin reduction ratio (P-value: 0.015). There was no statistically significant difference between group HDF post-3 months and group high flux as regard BS-AP reduction ratio (P-value: 0.212). Conclusion Sclerostin decreased by HDF. Yet, HDF has no effect on bone specific alkaline phosphatase in comparison to high flux hemodialysis.

Immune response to influenza vaccination in ESRD patients undergoing hemodialysis vs. hemodiafiltration

BackgroundOn-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD.Materials and methodsWe conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays.ResultsWe immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0–74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80–0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains.ConclusionsSeroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population.Trial registrationClinicalTrial.gov, NCT04122222.

Clinical Interventions and All-Cause Mortality of Patients with Chronic Kidney Disease: An Umbrella Systematic Review of Meta-Analyses.

Patients with chronic kidney disease (CKD) have altered physiologic processes, which result in different treatment outcomes compared with the general population. We aimed to systematically evaluate the efficacy of clinical interventions in reducing mortality of patients with CKD. We searched PubMed, MEDLINE, Embase, and Cochrane Database of Systematic Reviews for meta-analyses of randomized controlled trials (RCT) or observational studies (OS) studying the effect of treatment on all-cause mortality of patients with CKD. The credibility assessment was based on the random-effects summary estimate, heterogeneity, 95% prediction intervals, small study effects, excess significance, and credibility ceilings. Ninety-two articles yielded 130 unique meta-analyses. Convincing evidence from OSs supported mortality reduction with three treatments: angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers for patients not undergoing dialysis, warfarin for patients with atrial fibrillation not undergoing dialysis, and (at short-term) percutaneous coronary intervention compared to coronary artery bypass grafting for dialysis patients. Two treatment comparisons were supported by highly credible evidence from RCTs in terms of all-cause mortality. These were high-flux hemodialysis (HD) versus low-flux HD as a maintenance HD method and statin versus less statin or placebo for patients not undergoing dialysis. Most significant associations identified in OSs failed to be replicated in RCTs. Associations of high credibility from RCTs were in line with current guidelines. Given the heterogeneity of CKD, it seems hard to assume mortality reductions based on findings from OSs.

Development of an embossed nanofiber hemodialysis membrane for improving capacity and efficiency via 3D printing and electrospinning technology

A three-dimensional (3D) pattern was fabricated using a 3D printer to develop a hemodialysis nanofiber membrane with an embossed structure for portable or wearable hemodialyzers. The membrane of the embossed structure had a much larger surface area than that of the planar membrane structure. The high-flux hemodialysis membrane was prepared using a poly(methyl methacrylate)-graft-poly(dimethylsiloxane) (PMMA-g-PDMS) copolymer and polyamide 6 (PA6). The PMMA-g-PDMS copolymer is an organic-inorganic hybrid material in which the nanofiber diameter was controlled under 0.437 μm with a surface layer thickness of 50 (±20) μm. The polyamide 6 (PA6) nanofiber membranes were made with fibers 0.072 μm in diameter with a 0.14 μm pore size. This PMMA-g-PDMS/PA6 nanofiber hemodialysis membrane was modified for enhanced dialysis efficacy, and the modified membranes were evaluated based on clearance of saline and small molecules. Esterification and crosslinking reactions resulted in anionic hydrophilic hemodialysis membranes, and the fouling resistance is due to esterification of carboxylic acid groups (COOH) of sodium alginate with hydroxyl groups (OH) of polyethylene glycol, which generated a negatively charge surface. Thereby, repulsive electrostatic forces might be generated between the negatively charged blood cells and negative surface membrane. The water contact angle showed that the membrane hydrophilicity increased from 129 and 90° to 50°, and the total fouling parameter decreased to 0.112. The fouling resistance was enhanced due to the negatively charged membrane surface. Membrane contamination was measured by protein adhesion using a surface potential difference based on fluorescent whitening with zeta potential analysis, and the efficiency of creatinine removal was increased using a beta (β-cage) zeolite.

Feasibility of Online Haemodiafiltration in Sleep Apnoea: A Randomized Crossover Study

Background: Sleep apnoea is prevalent in dialysis patients. Previous studies identified excessive inflammation in ­patients with sleep apnoea. Online haemodiafiltration ­(OL-HDF) may reduce systematic inflammation through better clearance of middle molecules. We aimed to determine the feasibility of OL-HDF in sleep apnoea management. Methods: Eligible dialysis patients were screened for risk of sleep apnoea by nocturnal oximetry followed by a diagnostic sleep study to assess apnoea-hypopnea index (AHI). Patients with AHI ≥15/h were invited to a randomized crossover trial. The intervention was 2-month high-flux haemodialysis (HF-HD) followed by 2-month OL-HDF or vice versa with 1-month washout via HF-HD. Feasibility was assessed by patient recruitment and the primary outcome, severity of sleep apnoea (AHI). Secondary outcomes were pro-inflammatory cytokines, patient-reported daytime sleepiness, quality of sleep and health-related quality of life. Results: Of 65 participants at risk of sleep apnoea, only 15 were consented and randomized (mean age 70 years, 80% male, mean AHI 42.2/h). AHI was not statistically different between OL-HDF versus HF-HD (55.6/h vs. 48.3/h, p = 0.134); however, when sleep apnoea was stratified into obstructive and central apnoea, patients had less obstructive episodes after treated by OL-HDF (23.2/h vs. 18.6/h, p = 0.178); a sensitivity analysis was performed excluding outliers, and the treatment effect for obstructive episodes was found to be statistically significant (11.1 vs. 18.2/h, p = 0.019). Pro-inflammatory biomarkers and patient-reported outcomes were similar between OL-HDF and HF-HD. Conclusion: Patient recruitment was a major challenge in this feasibility study. OL-HDF may reduce obstructive sleep apnoea; however, the result needs to be confirmed by larger studies.

A tRial Evaluating Mid Cut-Off Value Membrane Clearance of Albumin and Light Chains in HemoDialysis Patients: A Safety Device Study

Background: A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. Methods: This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. Results: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had ­diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction –0.7 g/L, 95% CI –1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ –9.1 mg/L, 95% CI –14.4 to –3.7; kappa-FLC: Δ –5.7 mg/L, 95% CI –9.8 to –1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. Conclusions: Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. Trial Registration: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.

Asymmetric dimethylarginine compartmental behavior during high-flux hemodialysis

Aim The accumulation of uremic toxins, such as asymmetric dimethylarginine (ADMA), has emerged as one of the major cardiovascular disease-related risk factors in patients with end-stage renal disease (ESRD). Based on the low molecular weight of ADMA, hemodialysis (HD) should theoretically effectively remove ADMA. In this study, we investigated the clearance behavior of ADMA during high-flux HD. Methods Eight HD patients without residual renal function were included. Blood samples were collected at 0, 30, 60, 120 and 240 min after dialysis started, as well as 1 h and 48 h after dialysis. ADMA level was detected by HPLC-MS/MS. Herein, the ADMA level in blood cells and the ADMA protein binding rate were measured. Accordingly, the dialyzer extraction ratio was also determined. Results The reduction ratio (RR) of ADMA (corrected for hemoconcentration) was significantly lower, at only 37.21 ± 6.44%, than that of urea and creatinine (p < .05). Interestingly, its clearance from plasma was precipitous early in dialysis and became slowly from 60 to 240 min. Additionally, a greater inlet erythrocyte than plasma concentration was found for ADMA. The dialyzer extraction ratio was comparable between ADMA and creatinine or urea (83 ± 5% for ADMA vs. 84 ± 3% and 88 ± 2% for creatinine and urea, respectively; both p>.05). Urea and creatinine had a slight rebound ratio of less than 10% at 1 h after the completion of HD. In contrast, considerable rebound of approximately 30% was detected in ADMA. Conclusion This study suggests that ADMA may present a multicompartmental distribution that cannot be representatively reflected by the urea kinetics model.

Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: an observational prospective study

BackgroundOnline haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cut-off (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF.MethodsSix clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for β2-microglobulin (β2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs.ResultsAll three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P < 0.001). Conversely, predilution OL-HDF showed the greatest RR for β2M, whereas MCO HD and HF HD showed comparable RRs for β2M (predilution OL-HDF vs. MCO HD: 80.1 ± 4.9% vs. 72.6 ± 3.8%, P = 0.01). There was no significant difference among MCO HD, HF HD, and predilution OL-HDF in the RRs for κFLC (63.2 ± 6.0%, 53.6 ± 15.5%, and 61.5 ± 7.0%, respectively; P = 0.37), and FGF-23 (55.5 ± 20.3%, 34.6 ± 13.1%, and 35.8 ± 23.2%, respectively; P = 0.13). Notably, MCO HD showed improved clearances for FLCs when compared to HF HD or OL-HDF.ConclusionsMCO HD showed significantly greater RR of large middle molecules and achieved improved clearance for FLCs than conventional HD and OL-HDF, without the need for large convection volumes or high blood flow rates. This would pose as an advantage for elderly HD patients with poor vascular access and HD patients without access to OL-HDF.Trial registrationClinical Research Information Service (CRIS): KCT 0003009. The trial was prospectively registered on the 21 Jul 2018.

Use of Charcoal Hemoperfusion and High-Flux Hemodialysis in Carbamazepine Intoxication: Two Case Reports

Introduction: Carbamazepine (CBZ) is a drug used in the treatment of neurological and psychiatric disorders. Intoxication with CBZ is a serious condition that can result in coma, hemodynamic instability and death. Urgent management of CBZ intoxication is life saving and extracorporeal methods are used for removal of CBZ. It is also known that CBZ is highly protein-bound and charcoal hemoperfusion is the most effective extracorporeal elimination. We know that hemodialysis is also a technique for management of this drug. Case Presentation: We present two cases of CBZ intoxication, treated with two different methods, charcoal hemoperfusion and high-flux hemodialysis. The first patient who was receiving CBZ treatment for anxiety disorder was admitted to Bakirkoy Dr. Sadi Konuk Educational and Research Hospital, Istanbul, Turkey on 11th of December 2017, with complaints of dizziness and blurred vision. Vital signs were stable. Laboratory tests were normal. Serum CBZ level was 56 μg/mL (reference 4 - 12 μg/mL). The CBZ level was 15.6 μg/mL after charcoal hemoperfusion for 3 hours. The second patient was admitted to the emergency room on the 5th of February 2015, with blurred consciousness. The patient had taken CBZ for suicide. The CBZ level was 33 μg/mL and was 14.86 μg/mL after hemodialysis with high-flux membrane for 4 hours. Serum CBZ level decreased by 73% in the first patient who received charcoal hemoperfusion and by 55% in the second patient who received high-flux hemodialysis. Conclusions: In presenting these cases, we aimed to show the decrease of CBZ serum levels by using two different hemodialysis modalities in CBZ intoxication.

Effect of Hemodiafiltration on Self-Reported Sleep Duration: Results from a Randomized Controlled Trial

Introduction: Dialysis patients suffer from poor sleep duration and quality. We examined the self-reported sleep duration in patients randomized to either high-volume hemodiafiltration (HDF) or high flux hemodialysis (HD). Methods: Patients from 13 Brazilian dialysis clinics were enrolled in the HDFIT randomized controlled trial (RCT) investigating the impact of HDF on physical activity and self-reported outcomes. Self-reported sleep duration was taken from patient diaries recording sleep start and end time over a week during baseline, months 3 and 6, respectively. Sleep duration was analyzed by shift and nights relative to dialysis. Results: The HDFIT study enrolled 197 patients; sleep data were available in 173 patients (87 HD; 86 HDF). Patients’ age was 53 ± 15 years, 57% were white, 72% were male, 34% had diabetes, Kt/V was 1.54 ± 0.40, and albumin 3.97 ± 0.36 g/dL. Most patients reported sleeping 510–530 min/night. At 3 months, HDF patients slept 513 ± 71 min/night, HD patients 518 ± 76 min/night. At 6 months, HDF patients slept 532 ± 74 min/night, HD patients 519 ± 80 min/night. At baseline, 1st shift patients slept 406 ± 86 min the night before HD, 534 ± 64 min the night after HD, and 496 ± 99 min the night between 2 non-HD days. Compared to patients in the 2nd and 3rd shifts, patients dialyzed in the 1st shift slept less in the night before dialysis. Similar patterns were seen after 3 and 6 months. Conclusion: In our RCT, the dialysis modality (HDF vs. HD) had no effect on self-reported sleep duration. In both groups, dialysis in the 1st shift adversely affected self reported sleep duration.

Randomised trial on clinical performances and biocompatibility of four high-flux hemodialyzers in two mode treatments: hemodialysis vs post dilution hemodiafiltration

This prospective multicenter randomized comparative cross-over trial aimed at evaluating the influence of hemodialysis vs post-dilution hemodiafiltration with high-flux dialyzers in solute clearance and biocompatibility profile. 32 patients were sequentially dialyzed with Leoceed-21HX, Polypure-22S+, Rexsys-27H and VIE-21A. Primary outcome was β2-microglobulin removal. Secondary outcomes were (i) extraction of other uremic solutes (ii) parameters of inflammation and nutrition and (iii) comparative quantification of perdialytic albumin losses (using total ‘TDC’ vs partial ‘PDC’ collection of dialysate). Significant increases in removal rates of β2-microglobulin (84.7 ± 0.8 vs 71.6 ± 0.8 mg/L), myoglobin (65.9 ± 1.3 vs 38.6 ± 1.3 µg/L), free immunoglobulin light chains Kappa (74.9 ± 0.8 vs 55.6 ± 0.8 mg/L), β-trace protein (54.8 ± 1.3 vs 26.8 ± 1.4 mg/L) and orosomucoid (11.0 ± 1.1 vs 6.0 ± 1.1 g/L) but not myostatin (14.8 ± 1.5 vs 13.0 ± 1.5 ng/mL) were observed in HDF compared to HD when pooling all dialyzers. Rexsys and VIE-A use in both HD and HDF subgroups was associated to a better removal of middle/large-size molecules compared to Leoceed and Polypure, except β2-microglobulin for Rexsys. Inflammatory parameters were unchanged between dialyzers without any interaction with dialysis modality. Mean dialysate albumin loss was comparable between TDC and PDC (1.855 vs 1.826 g/session for TDC and PDC respectively). In addition, a significant difference in albumin loss was observed between dialyzers with the highest value (4.5 g/session) observed using Rexsys. Use of all dialyzers was associated with good removals of the large spectrum of uremic toxins tested and good biocompatibility profiles, with an additional gain in removal performances with HDF. Larger surface area, thinner wall and resultant very high ultrafiltration coefficient of Rexsys should be taken into account in its clear performance advantages.

Predicting Residual Function in Hemodialysis and Hemodiafiltration—A Population Kinetic, Decision Analytic Approach

In this study, we introduce a novel framework for the estimation of residual renal function (RRF), based on the population compartmental kinetic behavior of beta 2 microglobulin (B2M) and its dialytic removal. Using this model, we simulated a large cohort of patients with various levels of RRF receiving either conventional high-flux hemodialysis or on-line hemodiafiltration. These simulations were used to estimate a novel population kinetic (PK) equation for RRF (PK-RRF) that was validated in an external public dataset of real patients. We assessed the performance of the resulting equation(s) against their ability to estimate urea clearance using cross-validation. Our equations were derived entirely from computer simulations and advanced statistical modeling and had extremely high discrimination (Area Under the Curve, AUC 0.888–0.909) when applied to a human dataset of measurements of RRF. A clearance-based equation that utilized predialysis and postdialysis B2M measurements, patient weight, treatment duration and ultrafiltration had higher discrimination than an equation previously derived in humans. Furthermore, the derived equations appeared to have higher clinical usefulness as assessed by Decision Curve Analysis, potentially supporting decisions for individualizing dialysis prescriptions in patients with preserved RRF.

Single-use, single-pass tangential flow filtration using low-cost hollow fiber modules

Increasing pressures on biomanufacturing costs have led to renewed interest in the development of single-use technologies that can be readily adapted to continuous processing. The objective of this study was to use commercially available hollow fiber membranes, originally designed for high-flux hemodialysis, for single pass tangential flow filtration with high conversions. Experiments were performed with solutions of Immunoglobulin G (IgG) using polysulfone hollow fiber membrane cartridges with a surface area of 1.9 m2. The hollow fiber modules were able to provide more than 10-fold concentration of IgG in a single-pass with exit concentrations greater than 200 g/L. Stable operation was achieved during a continuous run for over a 120-h period with feed side pressure drops less than 1 kPa and transmembrane pressure drops less than 60 kPa. A single dialyzer was able to process 1.4 kg of IgG per day with a total cost of less than $0.004 per g of IgG. Flux-pressure profiles were in good qualitative agreement with a simple model accounting for concentration polarization effects and the variation of flux and pressure with axial position in the module. These results clearly demonstrate the potential of using these low-cost single-use hollow fiber modules for single-pass tangential flow filtration in continuous biomanufacturing.

Cardiovascular complications in hemodialysis patients: current approaches to prolong and improve quality of patients’ life

Cardiovascular complications are a leading cause of morbidity and mortality in dialysis patients. Cardiovascular mortality is more than 40% of the total mortality in this cohort of patients. Recently, there has been an increase in publications on the role of uremic toxins, including “middle molecules”, in the development and progression of cardiovascular complications in dialysis patients.&#x0D; Conventional low-flux (LF) hemodialysis well removes small molecular weight uremic toxins not bound with protein. Evidence for the role of "middle molecules" in the development of many complications, including cardiovascular complications, has contributed to the emergence and development of such dialysis therapy methods as high-flux (HF) hemodialysis, hemofiltration (HF) and hemodiafiltration (HDF).&#x0D; Further evolution of membrane technology has led to the development of protein-leaking membranes or super-flux or high cutoff (HCO) membranes. These membranes are capable of removing molecules in excess of the molecular weight of albumin. The use of these membranes is limited because of the risk of hypoalbuminemia.&#x0D; Today, the closest approximation to the natural glomerular membrane is the so-called Middle Cut-Off (MCO) membrane. The use of MSO membranes is implemented in a new method of dialysis therapy - expanded hemodialysis (HDx). The method is defined as a treatment where diffusion and convection are conveniently combined inside a hollow-fibre dialyser equipped with an MCO membrane. A standard hemodialysis machine is used for the HDx. Increased removal of large medium molecules in HDx may lead to an improvement of clinical outcomes, including a decrease of the cardiovascular events incidence, an all-cause and cardiovascular mortality reduction in dialysis patients.

Removal of Urea, β2-Microglobulin, and Indoxyl Sulfate Assessed by Absorbance and Fluorescence in the Spent Dialysate During Hemodialysis.

In this study, simultaneous removal assessment of marker molecules from three uremic toxin groups was performed during different hemodialysis treatment modalities using optical characteristics of spent dialysate. Results from optical measurements were compared with the results from chemical laboratory. Ten chronic dialysis patients, mean age 59 ± 15 years, were included in the study during 40 hemodialysis sessions. Low-flux hemodialysis (HD), high-flux hemodialysis (HF), and postdilutional online hemodiafiltration (HDF) with different settings were used. The reduction ratio (RR) and total removed solute (TRS) of three uremic solutes were determined: small molecular weight urea, middle molecular β2-microglobulin (B2M), and protein-bound indoxyl sulfate (IS). Concentrations of these solutes in the spent dialysate were measured by laboratory (lab) and optical (opt) methods, in the serum by laboratory methods, and calculated RR values in percentage were compared accordingly. Total removed solute was obtained from the total dialysate collection (TDC) using lab and opt methods. The highest RR values were found for urea and B2M, and the lowest for IS. The difference between RR of lab and opt results estimated as mean accuracy (BIAS) was ≤8.1% for all three solutes. Good correspondence between TRS lab vs. opt was achieved, resulting in strong linear correlation values R from 0.727 for urea to 0.971 for IS. Accuracy for TRS values as BIAS ± standard error (SE), comparing lab vs. opt, showed no statistical difference for any of the observed uremic solutes (P > 0.05). The accuracy of the optical method was not influenced by the dialysis modality (HD, HF, and HDF).

Predictors of nutritional and inflammation risk in hemodialysis patients.

Malnutrition and chronic inflammation are prevalent complications in hemodialysis (HD) patients. Different nutritional assessment tools are used to identify patients at risk. A composite and comprehensive malnutrition inflammation score (MIS) has been correlated with morbidity and mortality, and appears to be a robust and quantitative tool. Determine malnutrition risk profile in a sample of portuguese HD patients; determine the association of clinical and laboratory factors with MIS, and the impact of each parameter on MIS. We performed, between September 15th of 2015 and January 31st of 2016, a cross sectional analysis of 2975 patients, representing 25% of portuguese HD patients. 59% were men (66.7±14.8 years); 31% diabetic; 79% and 21% performed, respectively, high-flux HD and HDF. A MIS >5 was considered to indicate higher risk and was present in 1489 patients (50%). Amongst all parameters, comorbilities/dialysis vintage, transferrin, functional capacity, changes in body weight and decreased fat stores showed the higher impact, while albumin had one of the lowest impact on the nutritional risk. Higher age (>75 years, OR 1.71, p<0.001), diabetes (OR 1.25, p=0.026), lower P levels (OR 1.57,p=0.001), higher Ca levels (OR 1.51, p<0.001), higher ERI (OR 1.05, p<0.001), higher Kt/V (OR 2.14, p<0.001) and higher CRP (OR 1.01, p<0.001) were independently associated with a higher risk of MIS>5; higher nPNA (OR 0.29, p<0.001) and higher Pcreat (OR 0.88, p<0.001) were associated with a risk reduction of MIS>5 (95% CI). Routine clinical and analytic parameters were found to be associated with MIS range that might indicate higher risk, and may represent a simple alert sign for the need of further assessments.

High-Flux versus High-Retention-Onset Membranes: In vivo Small and Middle Molecules Kinetics in Convective Dialysis Modalities

Background: Patients undergoing maintenance hemodialysis (HD) exhibit increased levels of uremic toxins, which are associated with poor outcomes. Recently, new dialysis membranes have allowed clearance of solutes with higher molecular weight, without significant albumin losses high-retention-onset-HD (HRO-HD). Methods: Prospective crossover trial, in which 16 prevalent patients switched from high-flux HD (HF-HD) to online hemodiafiltration (olHDF) and HRO-HD for 4 weeks. The following variables were evaluated: pre- and post-dialysis serum concentrations of albumin, urea, phosphate (P), beta-2 microglobulin (β₂M), and total mass (TM) extraction and dialyzer clearance of urea, P, and β₂M. Results: Comparing HF-HD, olHDF, and HRO-HD, respectively, there were no differences regarding pre-dialysis serum concentrations of albumin (3.94 ± 0.36, 4.06 ± 0.22, and 3.93 ± 0.41 g/dL, p = 0.495), urea (166 ± 29, 167 ± 30, and 164 ± 27 mg/dL, p = 0.971), P (4.9 ± 2.1, 5.2 ± 1.6, and 4.9 ± 2.1 mg/dL, p = 0.879), and β₂M (31.3 ± 7.1, 32.6 ± 8.6, and 33.7 ± 5.9 µg/mL, p = 0.646). β₂M clearance was significantly lower in HF-HD in comparison to both olHDF and HRO-HD: 43 (37–53) versus 64 (48–85) mL/min, p = 0.013, and 69 (58–86) mL/min, p = 0.015, respectively. Post-dialysis β₂M serum concentration was higher in HF-HD in comparison to olHDF and HRO-HD: 11.6 (9.6–12.4) vs. 5.7 (4.5–7.0) µg/mL, p = 0.001, and 5.6 (5.3–7.6) µg/mL, p = 0.001, respectively. TM extraction of urea, P, and β₂M were similar across the 3 dialysis modalities. Conclusions: olHDF and HRO-HD were superior to HF-HD regarding β₂M clearance, leading to lower post-dialysis β₂M levels.

Long-term effect of medium cut-off dialyzer on middle uremic toxins and cell-free hemoglobin.

The medium cut-off (MCO) dialyzer has shown good clearance of large middle molecules, but its long-term effects are unclear. We investigated whether MCO hemodialysis (HD) over one year could reduce middle molecule levels and cell-free hemoglobin (CFH), without albumin loss. A prospective cohort study in 57 hemodialysis patients was conducted. The patients were assigned to the MCO dialyzer group or the high-flux dialyzer group, according to the HD machine they used. The reduction ratio (RR) and one-year changes in small and middle molecules and CFH were analyzed. Over a 12-month follow-up, MCO HD did not reduce the serum levels of middle molecules (lambda free light chain [FLC], from 135.7 ± 39.9 to 132.0 ± 39.1 mg/L; kappa FLC, from 168.2 ± 58.5 to 167.7 ± 65.8 mg/L; β2-microglobulin, from 25.6 ± 9.6 to 28.4 ± 4.8 mg/L) or albumin (from 3.96 ± 0.31 to 3.94 ± 0.37 g/dL). MCO HD provided excellent RR of lambda FLC (49.3 ± 10.3%), kappa FLC (69.6 ± 10.4%) and β2-microglobulin (80.9 ± 7.3%), compared to high-flux HD. CFH was also removed well during an MCO HD session (RR of CPH, 85.5 [78.7–97.3] %), but long-term change was not significant (from 57.8 [46.2–79.1] to 62.0 [54.6–116.7] mg/L). The MCO dialyzer can be used effectively and safely in conventional HD settings, but long-term effects on large middle molecules and CFH were not significant. Further studies are needed to verify clinical benefits of the MCO dialyzer.