Matching Efficacy of Online Hemodiafiltration in Simple Hemodialysis Mode

PUREMA H (referred to as PES) is an innovative dialysis membrane for enhanced low‐molecular‐weight (LMW) protein removal. The purpose of the study was to prove whether its efficacy in hemodialysis (HD) matches that of online hemodiafiltration (HDF) with conventional high‐flux membranes. In a prospective, randomized, cross‐over study on eight maintenance dialysis patients, treatment efficacy of HD with PES was compared with online postdilution HDF with the two synthetic high‐flux membranes polysulfone (referred to as PSU) and Polyamix (referred to as POX). Apart from the infusion of replacement fluid, which was set at 20% of the blood flow rate of 300 mL/min, operating conditions in HD and HDF were kept identical. Small solute and LMW protein plasma clearances as well as the reduction ratio (RR) of cystatin C and retinol‐binding protein were not different between the therapies. HDF with POX resulted in a significantly lower myoglobin RR as compared with HD with PES, and HDF with PSU. A 4% higher beta₂‐microglobulin RR was determined in HDF with PSU (73 ± 5%) as compared with PES in HD (69 ± 5%). The albumin loss was below 1 g for all treatments. Despite the fact that simple HD did not fully exploit the characteristics of PES, it achieved essentially similar LMW protein removal and albumin loss as compared with online postdilution HDF with the conventional synthetic high‐flux membranes PSU and POX. Therefore, HD with PES may have beneficial effects on the outcome of maintenance dialysis patients similar to high‐efficiency HDF.     

Vancomycin hemodialysis: Clearance differences between high‐flux hemodialysis and on‐line hemodiafiltration

The aim of this study was to analyze the differences between vancomycin clearance (Kd) with high‐flux hemodialysis (HFHD) and on‐line hemodiafiltration (OL‐HDF). The OL‐HDF therapy combined the diffusion and convective transport of solutes. To compare the Kd, a vancomycin loading dose of 1 g was administered intravenously post‐dialysis to 11 chronic and anuric (<100 mL/24 h) hemodialysis patients, undergoing HFHD and post‐dilutional OL‐HDF in consecutive therapies. Additional doses of 0.5 g were administered after 45 minutes at the end of each dialysis therapy during antibiotic treatment. Blood samples were drawn from arterial and venous lines at the start of hemodialysis sessions and at the first, second, third, and fourth hours. Additional samples were drawn at 15, 30, and 45 minutes after the end of dialysis therapy. Vancomycin plasma concentration, blood urea nitrogen (BUN), creatinine, and β₂‐microglobulin were measured. The patients’ hydration status was evaluated by bioimpedance analysis. The mean of vancomycin dialyzer clearance (Kd_dc) calculated was 110.8 ± 15 mL/min with HFHD and 146.8 ± 13.8 mL/min with OL‐HDF (P = 0.025). Significant differences were also obtained for β₂‐microglobulin clearance, Kd_dc 72.6 ± 15.4 mL/min with HFHD and 113.4 ± 24.2 mL/min with OL‐HDF (P = 0.012), whereas no differences were found for BUN or creatinine. Additionally, to analyze differences between HFHD and OL‐HDF, a variable volume dual pool mathematical model was developed to estimate the body clearance (Kd_bc), extraction mass (M_e), and inter‐compartment mass‐transfer coefficient (K₁₂) of each molecule. A higher vancomycin Kd_dc with OL‐HDF produced by convection improved removal of antibiotic; this can compromise achieving a therapeutic concentration target. We recommended evaluating increased loading doses of vancomycin and avoiding administration during OL‐HDF to assure adequate treatment.     

Benefits of first-half intensive haemodiafiltration for the removal of uraemic solutes

Aim: Haemodiafiltration (HDF) is the most efficient blood purification method and can remove a wide spectrum of solutes of different molecular weights (MW). The purpose of this study was to investigate whether the removed amounts of solutes, especially the larger molecules, could be increased by changing the HDF filtration procedure. Methods: A new first‐half intensive HDF treatment (F‐HDF) was designed, whereby convective clearance is intensively forced during the first half of a HDF session. We compared the removed amounts of solutes in the same group of nine patients treated by F‐HDF, constant rate‐replacing HDF (C‐HDF) and a high‐flux haemodialysis (HD). Results: F‐HDF can remove significantly larger amounts of α₁‐microglobulin (MG), molecular weight (MW) 33 000, compared with HD and C‐HDF (30.1 ± 15.1 vs 12.4 ± 0.3, 15.0 ± 3.1 mg, P < 0.01). Regarding the removal amounts and clear space of β₂MG, MW 11 800, there were no significant differences between the three treatment modalities. Regarding amounts of creatinine, urea nitrogen and phosphorus, there were no significant differences between the three treatment modalities. Conclusion: In post‐replacement HDF with a high‐flux membrane dialyzer, the method used in the present study in which replacement is completed during the first half of the process, is associated with a greater rate of larger molecule removal than the conventional uniform replacement method.     

Removal of Cell‐Activating Substances Using Dialyzers With Various Permeability Profiles

Despite multiple efforts to target an improvement in clinical outcomes of patients with end‐stage renal disease, several challenges must still be addressed. Dialysis patients are at a high risk for complications, as reflected by increasing mortality rates. The objective of this study is to assess the impact of the application of dialyzers with varying permeability profiles on the removal of cell‐activating substances from the blood of hemodialysis (HD) patients. Dialysate samples were collected using Revaclear 400 (RC) and MCO‐Ci400 (MCO‐CI). Total protein and solute marker concentrations were determined for the concentrated sample. The response of tubular epithelial cells (TECs) to the dialysate samples was assessed via measurement of interleukin 6, cell viability, and morphology. Proteomic analysis of the dialysate samples was performed using liquid chromatography coupled to tandem mass spectrometry. Treatment of TECs with the MCO‐CI dialysate resulted in significantly decreased cell viability compared with the RC dialysate. TECs incubated with samples from MCO‐CI lost their typical brick‐like shape and cell–cell connections. Proteomic analysis of dialysate samples indicated multiple pro‐apoptotic and pro‐inflammatory proteins, supporting the observed phenotype. Additionally, application of the MCO‐CI dialyzer allowed for more efficient removal of proteins associated with advanced chronic kidney disease stages. Collectively, the use of dialyzer with a higher permeability profile enabled more efficient removal of cell‐activating and toxic substances from the blood of HD patients. However, a further large‐scale study is needed to address benefits and associated risks for patients.     

Improvement of Intradialytic Hypotension in Diabetic Hemodialysis Patients Using Vitamin E‐Bonded Polysulfone Membrane Dialyzers

Currently, there are no detailed reports on the effects of vitamin E‐bonded polysulfone (PS) membrane dialyzers on intradialytic hypotension (IDH) in diabetic hemodialysis (HD) patients. This study was designed to evaluate changes in intradialytic systolic blood pressure (SBP) using “VPS‐HA” vitamin E‐bonded super high‐flux PS membrane dialyzers. The subjects were 62 diabetic HD patients whose intradialytic SBP fell by more than 20%. Group A comprised patients who required vasopressors to be able to continue treatment or who had to discontinue therapy due to their lowest intradialytic SBP being observed at 210 min (28 patients). Group B comprised patients who showed no symptoms and required no vasopressors but showed a gradual reduction in blood pressure, with the lowest intradialytic SBP seen at the end of dialysis (34 patients). The primary outcome was defined as the lowest intradialytic SBP after 3 months using VPS‐HA. Secondary outcomes included changes in the following: lowest intradialytic diastolic blood pressure, pulse pressure, pulse rate, plasma nitric oxide and peroxynitrite, serum albumin, and hemoglobin A1c. Group A's lowest intradialytic SBP had significantly improved at 3 months (128.0 ± 25.1 mm Hg vs. 117.1 ± 29.2 mm Hg; P = 0.017). Group B's lowest intradialytic SBP had significantly improved at 1 month (134.4 ± 13.2 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.047) and 3 months (139.1 ± 20.9 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.011). We conclude that VPS‐HA may improve IDH in diabetic HD patients.     

Efficacy and safety of expanded hemodialysis in hemodialysis patients: a meta-analysis and systematic review

BackgroundExpanded hemodialysis (HDx) is a new dialysis modality, but a systematic review of the clinical effects of using HDx is lacking. This systematic review and meta-analysis aimed to assess the efficacy and safety of HDx for hemodialysis (HD) patients.MethodsPubMed, the Cochrane library, and EMBASE databases were systematically searched for prospective interventional studies comparing the efficacy and safety of HDx with those of high flux HD or HDF in HD patients.ResultsEighteen trials including a total of 853 HD patients were enrolled. HDx increased the reduction ratio (RR) of β2-microglobulin (SMD 6.28%, 95% CI 0.83, 1.73, p = .02), κFLC (SMD 15.86%, 95% CI 6.96, 24.76, p = .0005), and λFLC (SMD 22.42%, 95% CI, 17.95, 26.88, p < .0001) compared with high flux HD. The RR of β2-microglobulin in the HDx group was lower than that in the HDF group (SMD −3.53%, 95% CI −1.16, −1.9, p < .0001). HDx increased the RRs of κFLC (SMD 1.34%, 95% CI 0.52, 2.16, p = .001) and λFLC (SMD 7.28%, 95% CI 1.08, 13.48, p = .02) compared to HDF. There was no significant difference in albumin loss into the dialysate between the HDx and HDF groups (SMD 0.35 g/session, 95% CI −2.38, 3.09, p = .8).ConclusionsThis meta-analysis indicated that compared with high-flux HD and HDF, HDx can increase the clearance of medium and large-molecular-weight uremic toxins. And it does not increase the loss of albumin compared with HDF.     

Removal of uraemic plasma factor(s) using different dialysis modalities reduces phosphatidylserine exposure in red blood cells.

BACKGROUND: Solute(s) retained during uraemia cause increased exposure of aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte membranes, and this phenomenon may be involved in the pathophysiology of uraemia by promoting abnormal erythrocyte interactions. METHODS: We examined in a prospective randomized cross-over fashion the ability of various dialysis modalities to remove the circulating uraemic factor(s) causing increased PS externalization in red cells. Each patient was treated with haemodialysis (HD) and with on-line haemodiafiltration (HDF) using standard high-flux polysulphone membranes or with the new polisulphone-based Helixone membrane to compare the effects of dialysis technique and membrane type on PS exposure. Removal of PS was assessed indirectly by measuring PS-expressing normal erythrocytes exposed to uraemic plasma or to ultrafiltrate obtained at various time points during the extracorporeal session. RESULTS: Removal of the uraemic plasma factor(s) causing PS exposure was demonstrated by the reduced ability of uraemic plasma at the end of dialysis to induce PS exposure in normal erythrocytes, and by the capacity of ultrafiltrate from the dialysate side of the dialyzer membrane to markedly increase PS-positive red cells. However, the degree of removal varied according to the dialyzer type and to dialysis technique. Removal was greater for on-line HDF using the Helixone membrane, intermediate and comparable with HD with Helixone and with on-line HDF using standard polysulphone, and lower for HD using polysulphone membrane. The putative uraemic compound causing PS exposure seems to be highly lipophilic, somehow associated with plasma proteins, and apparently having a molecular weight between 10 and 10.8 kDa. CONCLUSIONS: Uraemia is associated with retention of compound(s) that are lipophilic, possibly protein-bound and which cause an abnormal exposure of PS in erythrocytes. Our findings, that such compound(s) can be removed during dialysis and at higher rates with convection techniques, indicate a potential benefit for uraemic patients. The present results also seem to confirm the marked ability of high-flux Helixone membranes to eliminate high molecular weight solutes.     

Variation of clinical and laboratory features in chronic dialysis patients treated with high-flux hemodialysis after switching to online hemodiafiltration

Purpose

The study of online hemodiafiltration (HDF) benefits over high-flux hemodialysis (HD) raises great interest. The purpose was to compare clinical and laboratory parameters in patients treated with HD who were switched to HDF.

Methods

Forty-eight HD patients (study group) were switched to HDF, while other 521 patients remained on HD as a control group. During last 6 HD months and during first year of HDF, we determined in both groups the following parameters: monthly–weekly dialysis time, systolic and diastolic blood pressure, body mass index (BMI), interdialytic body weight gain (IBWG), blood flow rate (Qb), weekly erythropoietin-stimulating agents dose (EPO), single-pool Kt/V, calcium, phosphorus (P), hemoglobin and normalized protein catabolic ration (nPCR), plus every 3 months—albumin, parathormone (PTH), ferritin and transferrin saturation (TSAT). In both groups, parameters in the last 6 HD months were compared to those in the first 6 months and, respectively, to those in the first year of HDF.

Results

In the study group, albumin and nPCR were significantly higher in the HD period not only compared to the first 6 months of HDF, but also compared to the first year of HDF. IBWG and P were higher with HD compared to the first year of HDF, but not with the first 6 months. PTH, Kt/V, Qb and EPO were higher in both HDF periods. In the control group, albumin was significantly higher in the first 6 months after the switch, but it was significantly lower in the first year. BMI, ferritin, PTH, Kt/V, Qb, TSAT and weekly dialysis time were higher in both HDF periods, while nPCR, EPO, SBP and DBP were lower. IBWG and Hb rose only during the first year after the switch, while P was lower in the first year, but not in the first 6 months.

Conclusions

Nutrition, assessed by albumin, nPCR and BMI, was not improved by HDF compared to HD. With HDF, Kt/V and phosphorus control were better, similar results were observed in the control group. A larger EPO dose was needed with HDF for maintaining a similar hemoglobin level.     

The Influence of Colloid Osmotic Pressure on Hydrostatic Pressures in High‐ and Low‐Flux Hemodialyzers

The aim of this study was to examine the relationship between hydrostatic trans‐membrane pressure (TMP_h) and colloid osmotic pressure (COP) in low‐flux (LF) and high‐flux (HF) dialyzers. Hydrostatic pressures were measured in dialyzers distinguished by their ultrafiltration coefficient K_uf (16 and 85 mL/h/mm Hg) under constant dialysate flow and variable blood flow (Q_b) ranging from 0 to 400 mL/min using (i) alginate (70 kDa) dissolved in dialysate, (ii) diluted, undiluted, and concentrated plasma, or (iii) whole blood at different hematocrit, all in absence of ultrafiltration (UF). For a given fluid, TMP_h linearly increased with increasing Q_b. The intercept of the linear TMP_h to Q_b relationship correlated with measured COP with an average bias of 1.00 ± 2.26 mm Hg and a concordance correlation coefficient of 0.98. The slope of the linear TMP_h to Q_b relationship increased with increasing sample viscosity and was much larger in HF dialyzers under otherwise identical operating conditions, most likely because of increased internal filtration. The TMP_h to Q_b relationship measured in dialyzers in absence of UF can be described by the intercept related to measured COP and the slope related to internal filtration. This relationship could be of interest to estimate internal filtration and COP under in vivo conditions.     

Clinical Evidence on Hemodiafiltration: A Systematic Review and a Meta‐analysis

In this review, a systematic literature search and meta‐analysis were performed to assess the effects of hemodiafiltration (HDF) on clinical outcome, as compared with hemodialysis (HD). Furthermore, the relation between the convection volume in HDF and clinical outcome was studied. The literature search identified six randomized controlled trials (RCTs). In a meta‐analysis of these RCTs, HDF treatment was related to a decreased risk of mortality (RR: 0.84; 95% CI 0.73–0.96) and cardiovascular death (RR: 0.73; 95% CI 0.57–0.92). Post hoc analyses of the three largest RCTs suggested an inverse relation between the magnitude of convection volume and mortality risk. The evidence presented in this analysis supports a wider acceptance of HDF.     

Influence of Hemodialysis Membranes on Gene Expression and Plasma Levels of Interleukin-iβ

Abstract: Plasma levels of interleukin-iβ (IL-iβ) were measured in 10 normal subjects, in 11 nondialyzed end-stage renal failure (ESRD) patients, and in 22 hemodialysis (HD) patients. Of the HD patients, 7 were dialyzed with Cuprophan (CU), 7 with polymethylmethacrylate (PMMA), and 8 with polysulphone (PS) dialyzers. In normal controls, nondialyzed ESRD patients, and HD equipped with CU, PAMM, and PS dialyzers, plasma levels of IL-iβ were 10.73 ± 5.24 pg/ml, 9.97 ± 3.61 pg/ml, 13.17 ± 4.04 pg/ml, 15.16 ± 6.16 pg/ml, and 13.96 ± 5.47 pg/ml, respectively. There were no statistically significant differences among the groups (p ≥ 0.05). In contrast, the gene expression of IL-iβ for peripheral blood mononu-clear cells (PBMC) by in situ hybridization showed differences among the groups. The gene for IL-iβ for PBMC appears in HD equipped with different membranes, but not in cases of nondialyzed uremic patients and normal subjects. With computer imaging analysis, we carried out quantitative analysis of cells in in situ hybridization with an area of positive spots to an area of total cells. In HD with CU, PMMA, and PS, the results were 10.64 ± 1.07, 3.34 ± 0.74, and 3.27 ± 0.64%, respectively. The levels of IL-iβ gene expression in CU were higher than that in PMMA or PS. There were statistically significant differences (p ≤ 0.001) between CU and PMMA or PS and no significant difference between the PMMA and PS (p ≥ 0.05). We suggest measuring the gene expression of cy-tokines for PBMC and which may be better than measuring cytokine levels only for investigating the blood compatibility of dialyzers, which may help in understanding chronic complications of the dialysis procedure.     

Determining factors for hemodiafiltration to equal or exceed the performance of expanded hemodialysis

The aim of the study was to compare expanded hemodialysis (HDx) with hemodiafiltration (HDF) at different infusion flows to identify the main determinants, namely blood flow (Qb), replacement volume, infusion flow (Qi), ultrafiltration flow (Q_uf), filtration fraction (FF), and the point at which the effectiveness of HDF equals or exceeds that of HDx. We conducted a prospective, single-center study in 12 patients. Each patient underwent 12 dialysis sessions: six sessions with Qb 350 and six with Qb 400 mL/min; with each Qb, one session was with HDx and five sessions were with FX80 (one in HD, and four with Qi 50, 75, 90/100 mL/min or autosubstitution in postdilution HDF). The reduction ratios (RR) of urea, creatinine, ß₂-microglobulin, myoglobin, prolactin, α₁-microglobulin, α₁-acid glycoprotein, and albumin were compared intraindividually and the global removal score (GRS) was calculated. The mean replacement volume with Qb 350 mL/min was 13.77 ± 0.92 L with Qi 50 mL/min, 20.75 ± 1.17 L with Qi 75, 23.83 ± 1.92 L with Qi 90, and 27.51 ± 2.77 L with autosubstitution. Similar results were obtained with Qb 400 mL/min, and the results were only slightly higher with Qi 100 mL/min or in autosubstitution. The GRS was positively correlated with replacement volume with Qb 350 (R² = 0.583) and with Qb 400 (R² = 0.584); with Q_uf with Qb 350 (R² = 0.556) and with Qb 400 (R² = 0.604); and also with FF with Qb 350 (R² = 0.556) and with Qb 400 mL/min (R² = 0.603). The minimum convective volume in HDF from which it is possible to overcome the efficacy of HDx was 19.2 L with Qb 350 and 17.6 L with Qb 400 mL/min. The cut-off point of Q_uf at which HDF exceeded the effectiveness of HDx was 80.6 mL/min with Qb 350 and 74.1 mL/min with Qb 400 mL/min. The cut-off point at which FF in HDF exceeded the effectiveness of the HDx was 23.0% with Qb 350 and 18.6% with Qb 400 mL/min. In conclusion, this study confirms the superiority of postdilution HDF over HDx when replacement volume, convective volume, Q_uf, or FF exceeds certain values. Increasing the Qb in postdilution HDF manages to increase the convective dose and more easily overcome the HDx.     

In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments

Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis (HD). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (fHb). There are no absolute safety levels for fHb increase, indicating the need for an empirical evaluation using comparative testing. The increase in fHb levels was investigated in vitro by applying double‐needle double‐pump HD (HD‐DNDP), a new modality in which arterial and venous pumps both run continuously. fHb was measured during typical and worst‐case simulated dialysis treatments (double‐needle single‐pump HD [HD‐DNSP], hemodiafiltration [HDF‐DN], single‐needle double‐pump HD [HD‐SNDP], and HD‐DNDP) performed in vitro using bovine blood for 4 h. Hemolysis‐related indices (fHb%; index of hemolysis, IH; and normalized IH) were calculated and used for comparison. The increase in fHb during either HDF‐DN or HD‐SNDP with Artis and AK200 dialysis machines was similar, while the fHb at the maximum real blood flow rate (Qb_real) at the completion of the HD‐DNDP treatment on Artis was higher than that for HD‐DNSP using a Phoenix dialysis machine (fHb% = 1.24 ± 0.13 and 0.92 ± 0.12 for the Artis machine with HD‐DNDP at Qb_real = 450 mL/min and Phoenix with HD‐DNSP at Qb_real = 500 mL/min, respectively). However, the fHb levels increased linearly, and no steep changes were observed. The increases observed during HD‐DNDP were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured fHb trends are not predicted to have clinical side effects. HD‐DNDP treatment with Artis does not merit any additional concern regarding mechanical stress to RBCs compared with that observed for routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the fHb increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices.     

Cadmium Exposure and Osteoporosis: A Population‐Based Study and Benchmark Dose Estimation in Southern China

This study aimed to assess the association between osteoporosis and long‐term environmental Cd exposure through diet in southern China. A total of 1116 subjects from a Cd‐polluted area and a non‐Cd‐polluted area were investigated. All subjects met the criteria of having been living in the investigated area for more than 15 years and lived on a subsistence diet of rice and vegetables grown in that area. Besides bone mineral density, the levels of urinary markers of early renal impairment, such as urinary N‐acetyl‐β‐D‐glucosaminidase (NAG), α₁‐microglobulin, β₂‐microglobulin, and urinary albumin, were also determined. Urinary Cd concentrations of all studied subjects ranged from 0.21 to 87.31 µg/g creatinine, with a median of 3.97 µg/g creatinine. Multivariate linear regression models indicated a significant negative association of urinary Cd concentrations with bone mineral density. In logistic regression models, both categorical and continuous urinary Cd concentrations were positively associated with osteoporosis. Subjects in the second, third, and fourth quartiles of urinary Cd concentration had greater odds of osteoporosis compared with subjects in the first quartile (odds ratio [OR] = 3.07, 95% confidence interval [CI], 1.77 to 5.33; OR = 4.63, 95% CI, 2.68 to 7.98; OR = 9.15, 95% CI, 5.26 to 15.94, respectively). Additional adjustment for levels of urinary markers did not attenuate the associations. No evidence existed of an interaction between urinary Cd concentration and renal function using levels of urinary markers, and estimated glomerular filtration rate (eGFR). In all subjects, the benchmark dose and benchmark dose lower bound were 1.14 (0.61) and 2.73 (1.83) µg/g creatinine, with benchmark response set at 5% and 10%, respectively. The benchmark dose of urinary Cd was lower in women than in men. This study demonstrated an inverse association between the body burden of Cd and osteoporosis. The toxic effect of Cd on bone may occur in parallel to nephrotoxicity. © 2017 American Society for Bone and Mineral Research.     

Dialysis and Patient Factors Which Determine Convective Volume Exchange in Patients Treated by Postdilution Online Hemodiafiltration

Recent reports suggest a survival advantage for dialysis patients treated by postdilutional online hemodiafiltration (OL‐HDF) who achieve higher volume convective exchanges. As such, the factors associated with achieving higher convective volume exchange were determined. The convective exchange volumes during the midweek OL‐HDF session in a cohort of 653 patients with corresponding bio‐impedance measurements of volume status and sessional electronic records were audited. Mean patient age was 64.9 ± 14.9 years, 65.3% male, 47.7% diabetes, with 81.6% dialyzing using fistula access. Sessional substitution volume exchanged was 17.0 ± 3.5 L (83.8 ± 13.9 mL/min), with a filtration fraction of 23.3 ± 4.6%, sessional time of 3.8 ± 0.5 h, and blood flow 321 ± 28 mL/min. As expected, convection exchange volume achieved was associated with sessional time (β 3.24, P < 0.001), blood flow (β 0.03, P < 0.001), dialysate flow (β 0.03, P < 0.001), but also patient factors: postsessional intracellular water (ICW) (β 0.07, P = 0.002), and serum albumin (β 0.71, P = 0.011). In addition convective exchange was lower for diabetics (16.6 ± 3.0 vs. 17.3 ± 3.8 L, P < 0.01), and for patients with higher Davies co‐morbidity grades ( 16.6 ± 2.8 vs. 17.0 ± 3.6 vs. 17.9 ± 4.0 L), P = 0.01 respectively. As expected the convective volume exchanged with OL‐HDF was associated with sessional time and blood and dialysate flows. However, the convective volume exchange achieved was also associated with patient factors, including ICW, which is related to body cell mass and also co‐morbidity. Although some center practices can be modified to increase convective exchange, patient factors are not so readily remediable. As such, highly comorbid patients may not be able to achieve the higher volume convective exchanges reported to be associated with improved patient survival.     

Evaluation with micro‐CT of different anticoagulation strategies during hemodialysis in patients with thrombocytopenia: A randomized crossover study

In patients with enhanced risk for bleeding, heparin‐free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin‐coated dialyzers, we used a reference CT‐scanning technique and registered different clotting parameters to quantify coagulation with heparin‐coated versus non‐coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240 min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240 min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24 h, weighed, and scanned with micro‐CT at a resolution of 25 µm. After image reconstruction, the open, non‐coagulated fibers were counted in a representative cross‐section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin‐coated dialyzers had more patent fibers on micro‐CT versus non‐coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin‐coated versus non heparin‐coated membrane results in substantially less coagulated fibers during 4 h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation.     

A Sad but Forgotten Truth: The Story of Slow‐Moving Solutes in Fast Hemodialysis

When trying to optimize hemodialysis adequacy, it can be questioned whether one should focus on the dialyzer or on the patient. Another crucial question is whether the currently applied dialysis adequacy parameter, Kt/V_urea, is a reliable marker. For the small and water‐soluble solutes, recent advances in convective strategies and/or new dialyzer designs do not add much removal capacity. Depending on their specific kinetics, generally quite different from those of urea, small solute removal benefits from longer or more frequent dialysis. Clearance of beta‐2‐microglobulin (β₂M), a marker of middle molecule removal pattern, is improved with dialysis using more open and permselective membranes, as well as by using high convective volume strategies. Furthermore, longer and more frequent dialyses have highly favorable removal characteristics because they facilitate the retarded transport between plasmatic and extraplasmatic compartments over which these molecules are distributed. As β₂M may not be representative of other middle molecules, future kinetic analyses of alternative middle molecules will be of the utmost interest. Protein‐bound solute clearance is improved by convective techniques, but not by more open dialyzer pores. Knowledge of their kinetics should be helpful in interpreting the observation that frequent (but not longer) dialysis enhances protein‐bound solute removal. Hence, further technical improvements in dialyzers will have only a minor impact on dialysis adequacy, as retarded solute movement in the patient plays a decisive role. As urea kinetics is not representative of the kinetics of protein‐bound compounds, middle molecules, nor even of other small and water‐soluble solutes, it becomes self‐evident that urea clearance is a poor predictor of many aspects of dialysis adequacy.