High-flux Dialysis Research Articles

P1392ANALYSIS OF CALCIFYING POTENTIAL OF UREMIC SERUM FROM HAEMODIALYSIS PATIENTS TREATED WITH A MEDIUM CUT-OFF (THERANOVA) DIALYSER: A PROSPECTIVE, CROSS-OVER STUDY

Abstract Background and Aims The retention of a large number of solutes that are normally excreted or metabolized by the kidney is responsible for the classical symptoms of haemodialysis (HD) patients. These molecules are defined as uremic toxins and can be classified into three groups: small water-soluble molecules, middle molecules and protein-bound toxins. Recently, efforts were put in order to develop dialysis membranes that allow the removal of large-middle molecules without clinically relevant albumin loss. These dialysers are the medium cut-off (MCO) membranes, which allow the removal of middle molecules up to approximately 50,000 Da. We performed a prospective, open-label, controlled, cross-over pilot study comparing expanded HD (HDx) with MCO membrane Theranova and conventional HD in 20 patients. Method Ten patients underwent conventional HD high-flux dialyser and 10 patients underwent HDx for 3 months, later the patients switched and received the other treatment for a further 3 months. We then analyzed the pro-calcifying effect of patient uremic serum in a model of high-phosphate (Pi) induced calcification in vascular smooth muscle cells (VSMCs). Results In this study each patient was the control of himself and, interestingly, we found a tendency of less pro-calcifying potential of serum from patients when treated with HDx, in comparison with HD (6.6±1.1, 5.6±0.6 and 6.7±1.0, OD/mg protein, baseline HD, 0-3 HDx and 3-6 HD, months, respectively; and 4.7±0.7 vs 3.2±0.2, OD/mg protein, 0-3 HD vs 3-6 HDx, months, respectively) (Figure). Investigating the major mechanisms involved in high-Pi induced calcium deposition, we found that serum from patients when treated with HDx induced less necrosis in VSMCs, compared with HD (3.2±0.8 vs. 0.9±0.1, necrosis enrichment factor, 0-3 HD vs. 3-6 HDx, months, respectively). Nevertheless, no differences were found between the different dialysis treatment in the serum potential to induce apoptosis and to modulate the expression of a panel of genes involved in VSMC osteoblastic-differentiation such as BMP2, RUNX2, osteocalcin, MGP, OPN, and elastin. In the effort to characterize the difference in uremic toxin profile during the two different dialysis treatments, we measured a panel of protein-bound uremic toxins which have been shown to promote vascular calcification and /or bone loss and shown a significant increased removal by HDx of 3-indoxyl sulfate (30.6±13.2 vs -17.1±10.2 Δ%; 0-3 HD vs 3-6 HDx, months; p<0.05; and -21.1±11.4 vs 54.4±33.2 Δ%; 0-3 HDx vs 3-6 HD, months; p<0.05), indole 3-acetic acid (43.1±16.9 vs -2.3±10.9 Δ%; 0-3 HD vs 3-6 HDx, months; p<0.05), CMPF (61.8±27.6 vs -16.1±9.6 Δ%; 0-3 HD vs 3-6 HDx, months; p<0.05), and kynurenine (44.2±12.9 vs -0.2±6.8 Δ%; 0-3 HD vs 3-6 HDx, months; p<0.05). Conclusion These preliminary data suggest a role for HDx in reducing the calcifying potential of uremic serum. Our findings are promising and they need to be confirmed in larger studies.

P1534EFFECT OF HIGH-FLUX DIALYZER MEMBRANE SURFACE AREA ON SURVIVAL IN CHRONIC HEMODIALYSIS PATIENTS

Abstract Background and Aims High-flux dialyzer membrane material has been shown to improve mortality in hemodialysis (HD) patients. However, little is known about the impact of surface area of dialyzer membrane on prognosis in HD patients. A retrospective analysis was undertaken to investigate whether the difference in high-flux dialyzer membrane area affects survival rate. Method We observed 119 patients (43 females, mean age; 68 years, and HD duration; mean 84.4 months) maintained on HD for up to 5 years and 7 months. All patients were divided into two groups according to the surface area of dialyzer membranes; S group, 39 patients treated with the dialyzer membrane area of <1.5m2 (mean 1.0±0.1 m2) and L group, 80 patients treated with that of ≥1.5m2 (mean 2.0±0.2 m2). We analysed survival rate by Kaplan-Meier method. Results The patients were treated with four types of high-flux dialyzer membranes. S group included 21 patients with cellulose triacetate (CTA), 17 patients with polysulfone (PS) and 1 patient with polymethylmethacrylate. L group included 2 patients with CTA, 71 patients with PS and 7 patients with polyethersulfone (PES). Thirty-two patients, including 12 patients in S group and 20 patients in L group, had diabetes mellitus (DM). Survival rate was compared between the two groups, patients treated with CTA, PS and PES, and those with and without DM by Kaplan-Meier method. Type of dialyzer membranes used did not affect survival rate at the final observation (65.2% in CTA, 75% in PES and 50% in PS, p=0.26). The surface area of dialyzer membrane did not have a significant impact on mortality; survival rate at 3-year for S group, 71% vs L group, 77%, at 5-year for S group, 51% vs L group, 59%, and at the final observation for S group, 48%, vs L group, 58% (p=0.352). Among 32 diabetic patients, survival rate at the final observation did not differ between the two groups (S group, 33%, vs L groups, 45%, p=0.477). Among 87 non-diabetic patients (S groups; 27 patients), survival rate did not differ between the two groups at the final observation (S group, 56%, vs L group, 63%, p=0.575). Conclusion We conclude that difference in high-flux dialyzer membrane area is unlikely to affect survival rate in HD patients.

P1110IN VITRO CYTOKINE REMOVAL - COMPARISM OF CONVENTIONAL HDF AND HDX (MIDDLE-CUT-OFF-DIALYZER, BAXTER THERANOVA)

Abstract Background and Aims The removal of inflammatory mediators and cytokines is of great importance in the treatment of patients with acute or chronic renal failure. In patients with acute renal failure and sepsis, an attempt is made to achieve removal through the use of high-volume treatments or adsorbers in order to achieve better circulatory stability. In chronic dialysis patients, this has so far not been sufficiently addressed, but is important for mortality and cardiovascular events (MIA syndrome). Some studies show a superiority of HDF over conventional HD. By using new MCO filters in HD mode such as the Baxter Theranova (HDx), an improvement of cytokine status seems to be possible in both areas (chronic and acute). The effectiveness of MCO filters (HDx) compared to high flux hemodiafiltration in the removal of interleukins (interleukin 6, interleukin 10 and TNF (tumor necrosis factor) alpha will be assessed. Method The efficacy of HDx was compared with that of conventional high-flux dialysis filters (Fresenius FX80, HDF) in HDF mode. Based on real world conditions the ultrafiltration/substitution rate was set to 50 ml/min. (blood flow 200 ml/min., dialysate flow 500 ml/min.) No effective ultrafiltration was used. The measurements were performed in vitro in a 3l pool of fresh frozen plasma (citrate anticoagulated, with additional heparin during dialysis treatment). IL6 (24.5 kDa) IL10 (18.6 kDa, dimer)) and TNFalpha (17.4 kDa, trimer) were added to the plasma pool in concentrations of 1.5 μg/l each. This results in very high cytokine levels, as for example in severe sepsis. Samples were taken before and after the dialyzer for 180 minutes (after 5, 15, 30, 60, 120 and 180 minutes).For HDF the measured cytokine concentration was corrected for ultrafiltration rates. In addition to cytokines, albumin and total protein concentration were measured (ELISA Kit LEGEND MAX Human IL-6 / IL-10 / TNF-α; Biolegend and Cobas Mira Plus; Roche Kit LT-AB 0103 and LT-TP 0253). Every test was repeat 5 times. Results Theranova HDx showed higher removal rates of all tested cytokines over a period of 180 minutes. A comparison of the concentrations at the beginning and end of the measurements showed: IL-6 reduction - HDx about 77% / HDF about 63%. IL-10 reduction - HDx about 53% and HDF about 22%. TNF-α Reduction - HDx about 26%; HDF about 18% The concentration of albumin and total serum protein was not significant different during the treatments in both groups. Conclusion Hemodialysis therapy with Theranova HDx appears to be a superior or equal therapy option for the removal of cytokines. This opens up new treatment options for both acute renal failure and chronic dialysis patients, especially if citrate anticoagulation is necessary. The ultrafiltration rate in HDF was lower than recommended for high volume diafiltration,but as high as in our real world experience. Therefore the effect of HDF could be underestimated. Clinical studies with clinically relevant blood flow and ultrafiltration rates are still necessary.

Vitamin E-Bonded Membranes Do Not Influence Markers of Oxidative Stress in Hemodialysis Patients with Homozygous Glutathione Transferase M1 Gene Deletion.

Background: Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous GSTM1 gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous GSTM1 gene deletion. Methods: GSTM1 genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined. Results: Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups. Conclusions: Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.

Randomized controlled trial of medium cut-off versus high-flux dialyzers on quality of life outcomes in maintenance hemodialysis patients

Medium cut-off (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2 ± 20.8 vs. 59.8 ± 30.1, P = 0.042; 61.5 ± 37.6 vs. 39.0 ± 39.6, P = 0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29 ± 0.46 vs. 1.64 ± 0.64, P = 0.034; 0.25 ± 0.53 vs. 1.00 ± 1.47, P = 0.023, respectively). MCO dialyzers may improve patient-reported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers.

The Effect of High Flux versus Low Flux Dialyzers on Serum Fibroblast Growth Factor-23 (FGF-23) and Its Cardiovascular Implications in Prevalent Hemodialysis Patients

Background: Cardiovascular disease is the main cause of death in patients with end stage renal disease. Fibroblastic growth factor- 23 (FGF-23) is a novel phosphaturic hormone produced in the osteocyte. Patients with kidney disease complain of elevated levels of FGF-23 in response to hyperphosphatemia. Patients and Methods: This was a cross-over prospective study conducted on 30 patients on regular hemodialysis. The study period was 6 months, laboratory investigations for FGF-23, complete blood picture, s. urea (pre-dialysis and post-dialysis), serum albumin, serum electrolytes (Ca++ & PO4), alkaline phosphatase, PTH, serum ferritin, and lipid profile as well as echocardiography were obtained in the start of the study, after 3 months on maintained lowflux hemodialysis and 3 months after switching the patients to high-flux hemodialysis. Results: There was a highly significant reduction of FGF-23 level with high-flux dialyzers than with low-flux dialyzers. The adjusted difference in the absolute change in FGF-23 levels between the three months period of lowflux dialysis and the three months period of high-flux dialysis showed a highly significant reduction with high-flux than with low-flux (p= 0.000). There was a significant reduction of serum levels of PTH, calcium, phosphorus levels with high-flux dialyzers than with low-flux dialyzers, the adjusted difference was (p= 0.022), (p= 0.000), and (p= 0.006) respectively. Conclusion: FGF-23 levels were significantly higher in hemodialysis patients than in normal population. FGF-23 was better eliminated by high-flux dialyzers than low-flux dialyzers and high FGF-23 levels were associated with increased incidence of cardiac valve calcification. FGF-23 positively correlated with right ventricular systolic pressure.

Variations in Circulating Active MMP-9 Levels During Renal Replacement Therapy.

Renal replacement therapy (RRT) is complicated by a chronic state of inflammation and a high mortality risk. However, different RRT modalities can have a selective impact on markers of inflammation and oxidative stress. We evaluated the levels of active matrix metalloproteinase (MMP)-9 in patients undergoing two types of dialysis (high-flux dialysis (HFD) and on-line hemodiafiltration (OL-HDF)) and in kidney transplantation (KT) recipients. Active MMP-9 was measured by zymography and ELISA before (pre-) and after (post-) one dialysis session, and at baseline and follow-up (7 and 14 days, and 1, 3, 6, and 12 months) after KT. Active MMP-9 decreased post-dialysis only in HFD patients, while the levels in OL-HDF patients were already lower before dialysis. Active MMP-9 increased at 7 and 14 days post-KT and was restored to baseline levels three months post-KT, coinciding with an improvement in renal function and plasma creatinine. Active MMP-9 correlated with pulse pressure as an indicator of arterial stiffness both in dialysis patients and KT recipients. In conclusion, active MMP-9 is better controlled in OL-HDF than in HFD and is restored to baseline levels along with stabilization of renal parameters after KT. Active MMP-9 might act as a biomarker of arterial stiffness in RRT.

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.

Hemocompatibility of Polysulfone Hemodialyzers - Exploratory Studies on Impact of Treatment Modality and Dialyzer Characteristics.

The hemocompatibility of dialyzers for extracorporeal kidney replacement therapy (KRT) is of importance to minimize harmful reactions between blood constituents and the membrane. We investigated in these exploratory studies the hemocompatibility profile of several types of polysulfone dialyzers. Hemocompatibility of various high-flux polysulfone dialyzers were compared in two consecutive, prospective, randomized, crossover studies, each including 24 adult patients being at least 3 months on hemodialysis (HD) or on-line hemodiafiltration (HDF). These dialyzers, differing in membrane type, fiber geometry, sterilization method, and production technology, were each applied for 1 week in HD or HDF. Hemocompatibility was assessed through markers of complement activation, cell activation, coagulation, contact activation, and immunologic reactions. The patients in the two studies were on average 67±11 and 68±11 years old, 75% and 67% were male, and were on KRT for 5.4±5.0 and 4.4±3.6 years. The complement factors C3a and C5a increased early and transiently during treatment, less so with HDF than with HD, and with dialyzers combining wider inner fiber diameter (210 versus 185 µm) and advanced membrane type (Helixone plus versus Helixone). sC5b-9 increased in all study phases, reaching its highest level after 60 minutes, with lower values over the entire treatment (area under the curve) for HDF than HD, and for wider inner fiber diameter and advanced membrane type. Leukocytes decreased in the first 10 minutes, without significant differences between dialyzers. PMN elastase increased in the first hour, more so with HD than HDF. Thrombocytes decreased slightly in the first 30 minutes, with differences only between HDF and HD mode. IL-8 decreased from pre- to postdialysis, particularly on HDF. No differences were observed for kallikrein, IgE, and hsCRP. In these explorative studies we found indications to a comparable hemocompatibility profile of the investigated dialyzers. We observed distinctions in compounds between HDF and HD and for some dialyzer and membrane characteristics.

Preventive strategies and renal replacement therapies for patients with COVID-19

The current pandemic of coronavirus disease 2019 (COVID-19) spotlighted the vulnerability of patients with chronic kidney disease stage 5 on maintenance hemodialysis (HD) to the viral infection, A baseline hyperinflammatory state driven by factors such as the retention of uremic toxins afflicts these patients. Emphasis is placed on preparedness and prevention strategies for infection with this new COVID-19 Virus. Extracorporeal techniques can be helpful in the modulation of an immune dysregulated response, both in the severely ill and in the chronic HD patient. The use of high-flux (HF) dialyzers for HD is the standard of care. However, with HF membranes the effect is augmented when applied in a Hemodiafiltration mode, thanks for its dragging effect, on the other hand the use of superflux or Medium cut off dialyzers MCO are advantageous in removing the larger middle molecules with special respect to the cytokines release as a main cause of deterioration in those patients the use of more prolonged Hemodialysis, namely Continuous Renal Replacement Therapy (CRRT) as well the Prolonged Intermittent Renal Replacement Therapy (PIRRT) are considered best options as per its more prolongated time so compensate for the balance between production and elimination. Important issues are to improve the overall patients conditions on Maintenance Hemodialysis (MHD) in the term of maximizing the HD Dose, Nutritional support, treatment of any comorbidity as well inflammation as first step in preparedness of patients beside the strict and extensively adherent to preventive strategies that may improve the overall outcomes if they get infected with COVID-19.

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.

Advantages of expanded hemodialysis (HDx) over standard hemodialysis

Chronic kidney disease leads to the accumulation of a wide range of uremic toxins. Negative effects of uremic toxins are most likely due to the combined effects of many uremic solutes, including small molecules, middle molecules, and soluble protein-linked substances. Large and medium-sized molecules are directly associated with chronic inflammation and adverse effects, including major cardiovascular risks and consequently poor prognosis.&#x0D; Recent advances in chemical composition and new production techniques led to improved biocompatibility and selective permeability of dialysis membranes. Specifically, the creation of a new class of membranes provided the possibility to improve the clearance of medium to high molecular weight (MW) solutes (i.e. uremic toxins in the range of 5–50 kDa).&#x0D; The new HDx therapy (expanded HD) is the next evolution in hemodialysis, as it effectively targets the removal of large middle molecules. The HDx therapy is enabled by the THERANOVA dialyzer featuring an innovative membrane that combines a higher permeability than regular high-flux dialyzers with effective selectivity for large proteins.&#x0D; Expanded hemodialysis is an advanced therapy targeting large and medium-sized molecules that are currently not possible to remove by modern dialysis methods including traditional hemodialysis (HD) and hemodiafiltration (HDF). HDx became possible due to THERANOVA, a new dialyzer with an innovative membrane. The THERANOVA-based HDx provides a great new opportunity for dialysis patients, providing unique high-efficiency hemodialysis with the usage of already available infrastructure and standard HD workflows.

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.

Evaluation of the efficacy of a very high permeability dialyser and comparison with another high-flux dialyser in online haemodiafiltration.

Evaluation of the efficacy of a very high permeability dialyser and comparison with another high-flux dialyser in online haemodiafiltration.

Effects of a medium cut-off (Theranova®) dialyser on haemodialysis patients: a prospective, cross-over study.

BackgroundDespite significant advances in haemodialysis (HD) in recent decades, current dialysis techniques are limited by inadequate removal of uraemic solutes such as middle molecules and protein-bound uraemic toxins. Novel medium cut-off (MCO) membrane or ‘expanded haemodialysis’ (HDx) provides diffusive removal of conventional and large middle molecular weight uraemic toxins, with marginal albumin leak.MethodsThis prospective, open-label, controlled, cross-over pilot study compared HDx (novel MCO membrane Theranova® 400) and conventional HD in 20 prevalent HD patients. Biochemical, dialysis adequacy and safety measures (adverse events, infections and hospitalization frequency) were recorded. Ten patients underwent conventional HD high-flux dialyser and 10 patients underwent HDx for 3 months, and the patients then switched and received the other treatment for a further 3 months.ResultsTreatment with HDx was associated with a significant reduction in serum albumin concentration [median (interquartile range) reduction −0.45 g/dL (−0.575 to −0.05); P = 0.025]. However, median albumin levels were ≥3.5 g/dL and no patients had clinical symptoms of hypoalbuminaemia or needed intravenous albumin administration. The number of infections was lower in patients treated with HDx (n = 7/19) compared with patients treated with HD (n = 14/20; P = 0.03). Patients treated with HDx had reduced levels of interleukin (IL)-1β (from 0.06 ± 0.02 pg/mL versus 0.28 ± 0.18 pg/mL with HD) and IL-6 (6.45 ± 1.57 pg/mL versus 9.48 ± 2.15 pg/mL), while tumour necrosis factor-α levels remain unchanged.ConclusionsThis study demonstrates that the chronic use of the novel MCO dialyser Theranova® appears to be safe and well-tolerated, without serious side effects or hypoalbuminaemia, as well as fewer infections. These results need to be confirmed in larger randomized clinical trials.

ЭКСТРАКОРПОРАЛЬНАЯ КОРРЕКЦИЯ В РАННЕМ ПОСЛЕОПЕРАЦИОННОМ ПЕРИОДЕ У БОЛЬНЫХ С ТЯЖЕЛОЙ ОСТРОЙ ИШЕМИЕЙ НИЖНИХ КОНЕЧНОСТЕЙ

&#x0D; &#x0D; &#x0D; The clinical results of the use of Continuous Veno-Venous High Flux Dialysis (CVVHFD) in the early postoperative period in 37 patients with severe lower limb ischemia and an elevated preoperative level of blood creatinine were studied. The dynamics of total creatine phosphokinase, myoglobin, potassium in the early postoperative period was studied. The use of CVVHFD before the manifestation of the classic clinical presentation of renal dysfunction reduces the risk of adverse cardiopulmonary events from 26.1% to 14.3% and decreases the incidence of clinical renal dysfunction from 30.4% to 14.3%.&#x0D; &#x0D; &#x0D;

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.

MON-103 ALLO-HEMODIALYSIS: A NOVEL TREATMENT OPTION FOR PATIENTS WITH ACUTE AND CHRONIC KIDNEY FAILURE IN LIMITED-RESOURCE SETTINGS

Globally, between 2.2 and 7.1 million people may have died prematurely in 2010 because they did not have access to renal replacement therapy (Liyanage, The Lancet 2015). Social, economic, environmental, and technical barriers prevent a wide-spread use of current dialysis technologies. As a nephrology community, we have not yet developed impactful solutions to address this problem. In our research we systematically questioned long-held paradigms and conceptualized a novel treatment option that may have the potential to increase access to renal replacement therapy and reduce the loss of human life owing to kidney failure. We propose “alloHD” as a novel hemodialysis modality. With alloHD, the patient is dialyzed against a healthy subject (“buddy”). The buddy’s healthy kidneys then excrete the solutes and fluid transferred from the patient (Figure 1). Figure 1: Schematic alloHD setup with a pediatric patient (left) and an adult buddy (right). The buddy’s blood is pumped through the dialysate compartment and serves as dialysate; the two blood streams flow in opposite directions. In this version, ultrafiltration is accommodated by speed differentials of the patient-sided pumps. Using urea kinetic modeling, we simulated a wide range of clinically plausible scenarios and calculated the number of weekly alloHD sessions required to attain a target weekly standard Kt/V ≥ 2.0 when dialyzing pediatric and adult patients of different sizes against an adult buddy, using high-flux dialyzers and a treatment time of 4 hours each. We performed multiple alloHD simulations. Table 1 shows four representative results. Note that in these examples the blood flow rate (Qb) is the same for patient and buddy. AlloHD is a potentially life-saving treatment for patients with acute kidney injury (AKI) and end stage kidney disease (ESKD). Clearly, proof-of-concept animal studies are required, and risks for the buddy and patient need to be explored. Virus transfer is unlikely with intact dialyzer fibers, as the smallest known virus is 5x larger than average high-flux dialyzer pores. In AKI, catheters are likely the vascular access of choice for patient and buddy; in ESKD, arterio-venous fistulas are preferred. In addition to medical and technical considerations, a range of ethical and economic questions need to be addressed, e.g. buddy compensation and care delivery models. While we are cognizant of these challenges, we believe that alloHD expands the repertoire of dialysis therapy options, especially in the aftermath of disasters and in regions of the world where renal replacement therapy is currently out of reach for a large segment of the population.

Effect of High Flux Versus Low Flux Hemodialysis on Some Cardiovascular Risk Factors in Egyptian Children with End Stage Renal Disease.

Background Cardiovascular disease remains as the main cause of mortality in children with end stage renal disease (ESRD).Among the cardiovascular risk factors, dyslipidemia and inflammation are of great importance as they are both prevalent and modifiable risk factors. We aim to evaluate the effect of permeability of low-flux versus high-flux dialyzer on such 2 factors in children on regular hemodialysis (HD). Patients and Methods 48 children with ESRD were randomized into 2 groups. Group A used low-flux dialyzer, group B used high-flux dialyzer for 6 months. An initial and 6th month blood samples for lipid profile, serum albumin and serum high sensitivity CRP (hs CRP) were obtained. Statistical analysis was done. Results In the high flux group, there was a statistically significant difference in total cholesterol, HDL-cholesterol, triglyceride and hs CRP levels after 6 months when compared to baseline values of the same group, while LDL cholesterol and serum albumin showed no significant change. In the low flux group, results after 6 months didn’t show significant change in previously mentioned parameters when compared with its baseline values of the same group. Comparing these parameters between the 2 groups at 6 months, shows that high flux group has significantly lower total cholesterol, triglyceride, and hs CRP levels. Conclusion This study has demonstrated for the first time improvement of some markers of dyslipidemia and inflammation by using high-flux HD in children with ESRD. These results suggest that high-flux dialysis may benefit such young suffering population by reducing the atherogenic risk, cardiovascular morbidity and mortality.

High-permeability alternatives to current dialyzers performing both high-flux hemodialysis and postdilution online hemodiafiltration.

Most high-flux dialyzers can be used in both hemodialysis (HD) and online hemodiafiltration (OL-HDF). However, some of these dialyzers have higher permeability and should not be prescribed for OL-HDF to avoid high albumin losses. The aim of this study was to compare the safety and efficacy of a currently used dialyzer in HD and OL-HDF with those of several other high permeability dialyzers which should only be used in HD. A prospective, single-center study was carried out in 21 patients. Each patient underwent 5 dialysis sessions with routine dialysis parameters: 2 sessions with Helixone (HD and postdilution OL-HDF) and 1 session each with steam sterilized polyphenylene, polymethylmethacrylate (PMMA), and medium cut-off (MCO) dialyzers in HD treatment. The removal ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. A proportional part of the dialysate was collected to quantify the loss of various solutes, including albumin. Urea and creatinine RRs with the Helixone-HDF and MCO dialyzers were higher than with the other 3 dialyzers in HD. The β2 -microglobulin, myoglobin and prolactin RRs with Helixone-HDF treatment were significantly higher than those obtained with all 4 dialyzers in HD treatment. The β2 -microglobulin value obtained with the MCO dialyzer was also higher than that obtained with the other 3 dialyzers in HD treatment. The myoglobin RR with MCO was higher than those obtained with Helixone and PMMA in HD treatment. The prolactin RR with Helixone-HD was significantly lower than those obtained in the other 4 study sessions. The α1 -microglobulin and α1 - acid glycoprotein RRs with Helixone-HDF were significantly higher than those obtained with Helixone and PMMA in HD treatment. The albumin loss varied from 0.54 g with Helixone-HD to 3.3 g with polyphenylene. The global removal score values ((UreaRR + β2 -microglobulinRR + myoglobinRR + prolactinRR + α1 -microglobulinRR + α1 -acid glycoproteinRR - albuminRR )/6) were 43.7% with Helixone-HD, 47.7% with PMMA, 54% with polyphenylene, 54.8% with MCO and 59.6% with Helixone-HDF, with significant differences. In conclusion, this study confirms the superiority of OL-HDF over HD with the high-flux dialyzers that allow both treatments. Although new dialyzers with high permeability can only be used in HD, they are in an intermediate position and some are very close to OL-HDF.