Super high‐flux hemodialysis provides comparable effectiveness with high‐volume postdilution online hemodiafiltration in removing protein‐bound and middle‐molecule uremic toxins: A prospective cross‐over randomized controlled trial

Although high‐volume postdilution online hemodiafiltration (ol‐HDF) is superior to high‐flux HD in removing all kinds of uremic toxins and improving survival, this treatment is not available in most HD centers. The present study was conducted to compare the effectiveness in removals of protein‐bound (indoxyl sulfate [IS]), middle‐molecule [beta‐2 microglobulin (B2M) and alpha‐1 microglobulin (A1MG)], and small‐molecule uremic toxins between super high‐flux HD (SHF‐HD), HD with a novel SHF dialyzer and high‐volume postdilution ol‐HDF in a noninferiority fashion. Fifteen prevalent HD patients were randomly allocated into two sequences of 12‐week treatment periods of SHF‐HD treatment and later high‐volume postdilution ol‐HDF period or vice versa. Each treatment period was divided by a wash‐out phase of 4‐week high‐flux HD. Twelve of 15 patients could complete the study. When compared with high‐volume postdilution ol‐HDF (convective volume of 24.4 ± 3.52 L), SHF‐HD provided comparable reduction ratio values of IS, B2M, and A1MG with mean difference of 5.87 (95% confidence interval [CI] ‐1.63, 13.37), 1.98 (95% CI,‐0.21, 4.18), and 22.96 (95% CI, ‐1.91, 47.83), respectively. The spKt/Vurea was not different. The predialysis levels of all uremic toxins at baseline and after 12‐week treatment did not differ between both groups. Although albumin loss in dialysate in SHF‐HD was greater than high‐volume postdilution ol‐HDF, the serum albumin levels after 12‐week SHF‐HD treatment were significantly higher than baseline. In conclusion, SHF‐HD provides noninferior effectiveness to high‐volume postdilution ol‐HDF in removing various uremic toxins with significantly increased serum albumin levels despite higher albumin loss. SHF‐HD might be an effectively alternative treatment when high‐volume postdilution ol‐HDF is not available.     

Effect of hemodialysis and hemodiafiltration on uremic neuropathy.

This study was undertaken to compare the effect of 1 year hemodialysis (HD) or hemodiafiltration (HDF) treatment on peripheral neuropathy. Thus 21 of 42 patients on chronic HD (1-1.3 m2 cuprophane dialyzer, Qb 300 ml/min) were switched to HDF (1.3 m2 polysulfone dialyzer, Qb 400 ml/min, substitution volume 9-13 liters, ultrafiltration rate 60-70 ml/min), while the remaining patients were considered as a control group. Treatment time was scheduled both in HD and HDF to maintain adequate BUN levels in relation to protein catabolic rate. However, HDF provided a significantly greater weekly inulin (MW 5,000) clearance than HD (5.8 +/- 1.2 vs. 1.6 +/- 0.2 ml/min; p less than 0.001). HD and HDF groups were comparable for age, time on dialysis and starting electroneurographic parameters, which were on average within the normal range. After 1 year follow-up, creatinine, hematocrit, calcium, phosphate, PTH, BUN, protein catabolic rate and residual GFR were comparable in the two groups, whereas beta 2-microglobulin was significantly reduced in HDF patients (29 +/- 6.7 vs. 38.8 +/- 13.9 mg/l in HD patients, p less than 0.01). During the 1-year treatment, electroneurographic parameters did not change in HDF patients, whereas a significant decrease of ulnar motor nerve conduction velocity, ulnar muscle action potential amplitudes, median sensory nerve conduction velocity and peroneal muscle action potential amplitudes was detected in HD patients. We conclude that HDF might prevent the worsening of the electroneurographic indices occurring during chronic HD treatment, as it provides a more effective removal of middle and larger molecules than HD. The use of a more biocompatible membrane in HDF might further contribute to this favorable effect on uremic neuropathy.     

Impact of hemodialysis therapy on anemia of chronic kidney disease: the potential mechanisms

A significant and increasing number of chronic kidney disease (CKD) patients are treated with online hemodiafiltration (OL-HDF), even in the absence of more conclusive survival data. OL-HDF affords several clinical benefits including control of anemia of CKD, a common affliction in dialysis patients. In efforts to understand the underlying mechanisms that contribute to the purported benefits of OL-HDF, we examined the potential role and impact of OL-HDF on key stages of anemia and its correction: erythropoiesis of bone marrow, circulating erythrocytes and on anemia therapy. We review evidence that indicates OL-HDF may modulate key processes of anemia and its therapy, including underlying conditions and responses of uremic toxicity and inflammation that aggravate anemia. Our assessment indicates that OL-HDF favorably impacts anemia by not only eliminating putative uremic inhibitors that suppress erythropoiesis, reducing red cell destruction and increasing iron availability, but also by mechanisms restricting underlying inflammation and endothelial dysfunction that are crucial to both CKD and anemia.     

Comparison of dialyzers in on-line hemodiafiltration

At present we have a great variety of high-flux dialyzers whose characteristics in vitro seem similar. On-line HDF is a technique which combines diffusion with elevated convection and uses dialysate as replacement fluid. On-line HDF provides the highest clearances for small, medium-sized and large molecules and gives the best performance from the dialyzers. Conscious of this wide choice of dialyzers we evaluated the performance of different dialyzers in renowing small and medium-large molecules. Eleven patients were included in this study, 7 males and 4 females. Every patient received 11 on-line HDF sessions with Fresenius 4008B machine, Qi 100 ml/min or 6 L/h, QB 400 ml/min, QB 800 ml/min, UF 0.5 L/h and Td 60 min. Only the dialyzer was changed: 1.9 m2 cellulose triacetate (Tricea 190G), 2.1 m2 poly methyl methacrylate of PMMA (BK-2.1P), 1.8 m2 polyester-polymer Allol or PEPA (FLX-18GWS), 2.05 m2 acrylonitrile (Filtral 20), 2.1 m2 polyamide (Poliflux 2.1) and 1.8-2.4 m2 polysulfones (HF 80, BS-1.8S, APS-900, Arylane H9, Idemsa 2000, HdF 100). Arterial pressure, venous pressure and transmembrane pressure (TMP) were monitored. Plasma, urea, creatinine, phosphate, uric acid and beta 2m concentrations were measured at the beginning and at the end dialysis from arterial and venous blood lines, and arterial blood line with the slow flow method. Recirculation, dialyzer solutes clearance and solute reduction rates were calculated. No significant differences were found in arterial pressure, venous pressure and recirculation. Small molecule removal was similar except in BK-2.1P and HdF 100 dialyzers which were lower and higher respectively. There were differences in TMP and beta 2m removal among dialyzers employed. Mean TMP, beta 2m clearance and beta 2m reduction ratio were: Tricea 190G (TMP 336 mmHg, beta 2m K 79 ml/min and beta 2m reduction ratio 44.9%), BK-2.1P (TMP 485, beta 2m K 102 and beta 2mRR 48.3%), FLX-18 GWS (TMP 195, beta 2m K 140 and beta 2mRR 54.6%), Filtral 20 (TMP 245, beta 2m K 132 and beta 2mRR 54.1%), Poliflux 2.1 (TMP 209, beta 2m K 158 and beta 2mRR 56.0%), HF 80 (TMP 208, beta 2m K 160 and beta 2mRR 57.4%), BS-1.8S (TMP 186, beta 2m K 179 and beta 2mRR 59.6%), APS-900 (TMP 174, beta 2m K 176 and beta 2mRR 64.8%), Arylane H9 (TMP 206, beta 2m K 171 and beta 2mRR 59.9%), Idemsa 2000 (TMP 203, beta 2m K 169 and beta 2mRR 60.4%), HdF 100 (TMP 152, beta 2m K 186 and beta 2mRR 64.6%). CONCLUSIONS: Of the dialyzers evaluated in on-line HDF, cellulose triacetate and PMMA have a smaller beta 2m removal and their use is limited by an elevated TMP. The polysulfones provide greater beta 2m removal with lower TMP, particularly the APS-900 and HdF 100 dialyzers. The acrylonitrile, PEPA and polyamide are intermediate.     

A critical assessment of uremia research

There are considerably fewer randomized controlled trials investigating hemodialysis (HD) than other fields of internal medicine, and no significant improvements have been observed over time. Only the National Cooperative Dialysis Study and the HEMO trial were based on hard endpoints such as morbidity and mortality, but neither considered on-line hemodiafiltration or super-flux membranes, which are thought to provide a number of advantages in terms of the cardiovascular condition of uremic patients. However, results of well-designed clinical trials showing that increasing convection may improve the clinical outcome of HD patients are still lacking. The need for maximizing removal of uremic toxins calls for more frequent HD sessions, but this may be affected by many organizational problems. Therefore, well-designed, long-term clinical trials are urgently needed to investigate which currently available therapeutic instruments can improve the clinical outcome of uremic patients.     

Internal filtration-enhanced hemodialysis is a cost-effective treatment in view of solute removal

By modifying dialyzer module design, internal filtration (IF) within a dialyzer is enhanced to increase convective solute transport. Thus, it can be an alternative to hemodiafiltration with no requirement of substitution fluid or additional complex machines. Cost-effective analysis was conducted in three modes of therapy: high-flux hemodialysis, on-line hemodiafiltration and IF-enhanced hemodialysis. In IF-enhanced hemodialysis, cost-effectiveness of small solute removal is comparable with high-flux hemodialysis and that of beta(2)-microglobulin removal is the best. It is concluded that IF-enhanced hemodialysis is the most cost-effective therapy mode in comprehensive overall solute removal.     

Convective dialysis therapies, current status and perspective

When introduced in the 1970s, convective dialysis therapies were considered an attractive alternative to hemodialysis (HD), but technical and economical limitations prevented wide clinical application. Today, these therapies (i.e. hemofiltration and hemodiafiltration) are receiving renewed interest from the renal community. The main reason is the disappointment with current chronic dialysis therapy, which despite continuous integration of technical and pharmaceutical progress, has not provided significantly improved survival. The recent HEMO study showed that HD, even when administered at high dose and with high-flux membranes, has reached the limit of benefit for a representative dialysis population. At the same time there is new evidence supporting convective therapies. The extended range of solutes that is removed by convection as opposed to diffusion includes many molecules associated with uremic symptoms and complications. The hemodynamic stability characteristic of convective therapies is confirmed also in comparison with modern HD. Observational data indicates a survival benefit for patients treated with large volumes of convection. Continuously applied convective therapies are the preferred choice in severe cases of acute renal failure, and new membrane development may take these therapies to new applications of blood purification in the intensive care unit.     

Valoración de la influencia de la superficie de la membrana y el flujo sanguíneo en dializadores de medio cut-off

IntroductionRecently, a new class of dialyzers, medium cut-off membranes (MCO), designed to improve the permeability, which could provide an efficacy similar to hemodiafiltration, have been incorporated into our therapeutic possibilities. To increase the knowledge about its use, the objective of the study was to evaluate the effect of the surface and blood flow (Qb) on the depurative efficacy in the MCO membranes.Material and methodsWe included 19 patients in the hemodialysis. Each patient received 6 sessions, in which the membrane surface was varied, from 1.7 to 2.0 m², and/or the Qb (300, 350, 400 or 450 mL/min). In each session, different solutes were determined at the beginning and end of dialysis.ResultsThe surface change of the dialyzer did not show significant differences in the removal of small or large molecules, without changes in albumin loss. The increase in Qb was accompanied by an increase in clearance of small molecules, without showing differences in the percentage reduction of β₂-microglobulin, myoglobin, prolactin, α₁-microglobulin and α₁-acid glycoprotein, except for some comparison with Qb 450 mL/min. There were also no differences in the loss of albumin in the dialysis fluid, less than 2.5 g in all situations.ConclusionThe increase of the surface area from 1.7 to 2.0 m² in the MCO dialyzer has not meant a greater depurative effectiveness. In these dialyzers the increase of Qb does not seem to be as determinant as in hemodiafiltration except for the clearance of small molecules.     

Una nueva generación de triacetato de celulosa adecuado para hemodiafiltración on-line

Background

Online haemodiafiltration (OL-HDF) is currently the most effective dialysis technique that also improves survival. To date, high permeability membranes with low albumin loss, such as polysulfone, polyamide and polyacrylonitrile membranes have been the most widely used. However, the initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has expanded. The aim of the study was to ascertain whether the latest generation asymmetric CTA membranes are more effective in obtaining high convective transport.

Improvement of nutritional status in patients with short daily on-line hemodiafiltration

Daily dialysis have showed excellent results because a higher frequency of dialysis is more physiological and it decreases the fluctuation of liquid, solutes and electrolytes. Improvement of certain causes of anorexia such as postdialysis fatigue, reduction in fluid overload, uremic milieu, medium and large-sized molecule removal could be observed with daily dialysis. The aim of this study was to evaluate nutritional parameters when thrice weekly on-line hemodiafiltration (OL-HDF) were switched to daily OL-HDF. 24 patients have been studied. Eight patients, 6 males and 2 females, mean age of 65.9 +/- 14 years, on thrice weekly 4 to 5 hours OL-HDF were switched to 2 to 2.5 hours six times per week. Dialysis parameters were the same in both periods and only frequency and dialysis time were changed. Other sixteen patients, mean age of 68.4 +/- 14 years, were a control group which dialysis parameters were maintained. Clinical and biochemical outcome were carried out over twelve months. Daily OL-HDF group: Dry weight increased from 67.8 +/- 8 kg at baseline to 68.5 +/- 8 kg after three months, 69.3 +/- 8 kg after six months (NS), 69.5 +/- 8 kg after nine months (p < 0.05) and 70.8 +/- 8 (p < 0.01) after one year. Mean nPCR increased from 0.93 +/- 0.2 g/kg/d on baseline to 1.18 +/- 0.3 after three moths (P < 0.0-5), 1.13 +/- 0.2 after six months (NS), 1.06 +/- 0.2 after nine months (NS) and 1.10 +/- 0.2 after twelve months (NS). There were no significant changes in serum protein, albumin, prealbumin, transferrin, total cholesterol, HDL-c, LDL-c and triglycerides (TG). There were no changes in control group. Mean dry weight was 62.3 +/- 9 kg at baseline and 62.1 +/- 10 kg after one year. Mean nPCR was 0.97 +/- 0.2 g/kg/d on baseline and 1.03 +/- 0.2 g/kg/d after one year. Neither there were changes in serum protein, albumin, transferrin, total cholesterol, HDL-c, LDL-c and TG. Improvement in nutrition status has been observed with the change from thrice weekly OL-HDF to short daily OL-HDF. Increased appetite and protein intake was accompanied by a dry body weight increase of three kg after twelve months.     

The use of a low-flux hemo-dialyzer is associated with impaired platelet aggregation in patients undergoing chronic hemodialysis

In patients with chronic hemodialysis (HD), both abnormal thrombotic and bleeding events are commonly observed. Uremic platelet dysfunction is one of the important attributing factors. Moreover, HD may also result in aggregation dysfunction of platelets during the therapeutic procedure. However, how the HD process affects platelet and coagulation function is unknown and dialyzer membrane flux could have an impact on it. We aimed to compare the impacts of low-flux and high-flux HD on the platelet function of patients undergoing chronic HD. This was a cross-sectional study conducted in the HD unit of E-Da hospital in Taiwan. A total of 78 patients with maintenance HD three times per week for more than one year, including 40 with high- and 38 with low-flux hemodialysis, were recruited. Their platelet functions were evaluated using an in vitro platelet function analyzer (PFA-100) before and after the HD session. Of the 78 patients undergoing HD, 60 (76%) had prolonged pre-dialysis collagen/epinephrine (CEPI) and collagen/adenosine diphosphate closure times. Those receiving low-flux dialyzer had a significant increase in CEPI closure time (pre-dialysis 212.3 ± 62.1 seconds. post-dialysis 241.5 ± 64.3 seconds, P = .01), but not collagen/adenosine diphosphate closure time, after HD. After adjusting confounding factors, only the low-flux dialyzer demonstrated an independent association with the prolonged CEPI closure time after HD therapy (odds ratio = 23.31, 95% CI: 1.94–280.61, P = .01). We observed that impaired platelet aggregation is prevalent in patients undergoing chronic HD. Therefore, the use of low-flux dialyzers may further worsen platelet aggregation after dialysis. Patients with uremic bleeding diathesis should take precautions. We suggest that further studies using flow cytometry should be conducted to explore the mechanism of dialysis flux and platelet activity during HD.     

Electrolyte concentration during haemodialysis and QT interval prolongation in uraemic patients.

AIMS: To assess the effect of different combinations of potassium and calcium concentrations on QT interval in the dialysis bath in uraemic patients. METHODS AND RESULTS: Sixteen haemodialysis (HD) patients underwent a 24 h Holter recording before and during HD sessions with six randomized combinations of electrolytes concentrations of the dialysis bath (K(+), 2 and 3 mmol/L; Ca(2+), 1.25, 1.5, and 1.75 mmol/L). The effect of different dialysis baths on QT interval was significant (P < 0.05). The longest mean QTc was observed with the lowest K(+) (2 mmol/L) and Ca(2+) concentrations (1.25 mmol/L), whereas the shortest mean QTc was observed with the highest K(+) (3 mmol/L) and Ca(2+) concentrations (1.75 mmol/L). QTc was >440 ms in 9 of 16 patients (56%) at the lowest Ca(2+) and K(+) concentrations, and in 3 of 16 patients (18%) at the highest electrolytes level. Changes in QTc during the HD sessions were inversely correlated with that in total Ca and Ca(2+) plasma concentrations (P < 0.0001). CONCLUSION: Changes in ventricular repolarization duration associated with HD largely depend on the concentrations of Ca(2+) and K(+) in the dialysis bath. These findings may have important implications for the choice of the electrolytes concentration of the dialysis bath during the HD session.     

Effects of Dialysis Purity on Uremic Dyslipidemia

Dyslipidemia, a prominent feature of end-stage renal disease, is considered a risk factor for premature atherosclerosis in hemodialysis (HD) patients. Dyslipidemia is related to loss of kidney function as well as use of low-flux cellulosic dialyzer membranes, but the effects of dialysate purity are unknown. Forty-eight incident HD patients started high-flux polysulfone maintenance HD, either with conventional (potentially contaminated) or with on-line produced ultrapure dialysate. The quality of the dialysis fluid (CFU/mL, endotoxin concentration), markers of inflammation (C-reactive protein, Il-6), and parameters of the lipid profile and oxidative stress (oxidized low-density lipoprotein) were measured before initiation of HD, and after 6, 12 and 24 months on HD. Compared to baseline, treatment with conventional (mildly contaminated) dialysate significantly increased the uremic low-grade systemic inflammatory response syndrome (SIRS), augmented uremic dyslipidemia (triglycerides by +21%, and high-density lipoprotein (HDL) cholesterol by −10%) and enhanced oxidative stress. In contrast, the use of ultrapure dialysate significantly decreased uremia-associated SIRS, dyslipidemia (triglycerides −7% and HDL cholesterol +11%) and oxidative stress. Ultrapure dialysis fluid improves potential parameters of cardiovascular risk by decreasing inflammatory reactions, improving uremic dyslipidemia and lowering oxidative stress.     

Enhanced functional performance characteristics of a new polysulfone membrane for high-flux hemodialysis

Elimination of uremic solutes with molecular weights up to 60 kD, without significant loss of albumin is an important therapeutic goal to optimize outcomes in chronic hemodialysis patients. To characterize a newly developed polysulfone dialyzer (APS-650) a comparative analysis was performed with a highly advanced polysulfone dialyzer (F-60S) including 22 stable chronic hemodialysis patients. Diffusive clearances were determined, and albumin loss was calculated. The elimination profile of uremic solutes up to 32.0 kD was assessed in vivo by sieving coefficients, clearances, and reduction ratios of beta(2)-microglobulin (11.8 kD), myoglobin (17.2 kD), prolactin (23.0 kD), and alpha(1)-microglobulin (32.0 kD). Hemocompatibility was tested in serial measurements of total white blood cell count, platelet count, C3a, and neutrophil elastase. No significant albumin loss was detected. Significantly higher sieving coefficients, clearances, and reduction ratios for proteins with molecular weight up to 32.0 kD were demonstrated with the newly developed polysulfone membrane. Both polysulfone membranes were equal concerning hemocompatibility parameters. The APS-650 dialyzer allowed optimized hemodialysis treatment with respect to clearance of medium-sized uraemic solutes by high-flux dialysis.     

One year of clinical experience in postdilution hemofiltration with online reinfusion of regenerated ultrafiltrate

BACKGROUND/AIMS: Hemofiltrate reinfusion (HFR) is characterized by the use of regenerated ultrafiltrate as replacement fluid. We set up a new technique, postdilution HFR (PD-HFR), aiming at increasing purification efficiency, treatment tolerance and at reducing inflammatory states. METHODS: We performed PD-HFR in 6 uremic patients during 1 year. Dialysis efficacy, dialyzer blood loss and the behavior of cytokines were evaluated. RESULTS: No pyrogenic reactions or other adverse events were recorded. Treatment tolerance was excellent. We observed high urea extraction rates and optimal Kt/V values, high beta2-microglobulin (beta2m) extraction rates and a decrease in dialyzer blood loss; also IL-6 and TNF-alpha decreased significantly. CONCLUSIONS: Inversion of the standard HFR configuration has allowed us to improve the removal of both urea and beta2m, and to decrease dialyzer blood loss, with an optimal tolerance. Moreover, the decrease in cytokine levels might attenuate the uremic microinflammatory state.     

Dialysis in public and private hospitals in Queensland

Background: Clinical outcomes for patients treated in public and private hospitals may be different. Aim: The aim of the study was to compare the characteristics and outcomes of patients receiving dialysis at public and private hospitals in Queensland. Methods: Incident adult dialysis patients in Queensland registered with the Australia and New Zealand Dialysis and Transplant Registry between 1999 and 2009 were classified by dialysis modality at either a public or private hospital. Outcomes were dialysis patient characteristics and survival. Results: Three thousand, three hundred and ten patients commenced dialysis in public hospitals, 1939 haemodialysis (HD) and 1371 peritoneal dialysis (PD). Seven hundred and ninety-three patients commenced dialysis in private hospitals, 757 HD and 36 PD. Compared with public HD, private HD patients were older, had more coronary artery disease and less diabetes, and were more likely to live in an urban area. Public HD patients were more likely to be obese and referred late to a nephrologist. Nearly all indigenous patients were managed in public hospitals. Private patients were more likely to have an arteriovenous fistula or graft at first HD (P < 0.001) but not after excluding late referrals (P = 0.09). Public hospitals provided longer HD sessions and more HD hours per week for all age groups except 75+ years. Compared with public hospital HD, patient survival adjusted for multiple variables was comparable for private hospital HD (hazard ratio 1.20 (95% confidence interval 0.98-1.46, P = 0.07)) but worse for public PD (hazard ratio 1.14 (95% confidence interval 1.05-1.24, P = 0.002)). Conclusion: Private HD patients are older and less likely to be diabetic than public patients. Patient survival is worse for public PD than public HD.     

A switch to high-flux helixone membranes reverses suppressed interferon-gamma production in patients on low-flux dialysis

Long-term hemodialysis (HD) induces an inflammatory response and is associated with a suppressed cellular immune response manifested, in part, by impaired interferon (IFN-gamma) production. We investigated the effect of high-flux HD using the synthetic Helixone membrane and ultrafiltered dialysate on plasma levels of inflammatory mediators and on the whole blood production of IFN-gamma. METHODS: Twelve ESRD patients were dialyzed under low-flux HD (polysulfone F6) and again after 6 weeks of high-flux HD (Helixone FX100). Ultrafiltered bicarbonate dialysate without bacterial growth and no detectable endotoxin was used throughout the study. Plasma levels of urea, albumin, beta(2)-microglobulin (beta(2)-m), interleukin (IL)-6, C-reactive protein (CRP), IL-1 receptor antagonist (IL-1Ra), IL-18, and IL-18-binding protein (IL-18BP) were measured. In addition, the Staphylococcus epidermidis-induced production of IFN-gamma and IL-18 was assessed in whole blood cultures of HD patients as well as in 9 healthy subjects. RESULTS: Plasma levels of urea, albumin, IL-6, IL-1Ra and CRP were not significantly different between high-flux and low-flux HD. In contrast, beta(2)-m levels decreased significantly by 31% with high-flux Helixone (p < 0.002). Stimulated whole blood production of IFN-gamma was reduced in low-flux HD but increased to near normal levels after 6 weeks of high-flux HD. Plasma levels of free IL-18 and its specific inhibitor IL-18BP were not different between the two dialyzer membranes. CONCLUSION: Compared to low-flux polysulfone HD with ultrafiltered dialysate, high-flux HD with the synthetic Helixone membrane did not result in a significant change in plasma levels of proinflammatory (IL-6, CRP, IL-18) and anti-inflammatory (IL-1Ra, IL-18BP) cytokines. However, high-flux HD restores whole blood IFN-gamma production without significant changes in free IL-18. Therefore, the immune modulation in high-flux HD is likely due to removal of inhibitors of IFN-gamma production other than IL-18BP.     

Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high-flux hemodialysis?

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular–weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.     

On-line hemodiafiltration and high-flux hemodialysis: comparison of efficiency and cost analysis

With on-line hemodiafiltration (HDF), low molecular weight substances are predominantly cleared by diffusion while middle molecules such as ß2-microglobulin (ß2M), an amyloidogenic factor, are removed mainly by convection. The objectives of this study are to evaluate the cost-effectiveness and safety of on-line HDF with dialyzer reuse, and to compare HDF and high-flux hemodialysis (HD) with respect to ß2M removal, urea kinetics (Kt/V) and symptom relief in those patients having dialysis-related amyloidosis. Ten chronic HD patients were put on post-dilution HDF for a period of 14.2 ±7.1 months. The AK 100 ULTRA system was used for on-line preparation of substitution fluid. These patients were then switched over to high-flux HD for a period of 4.6 ±3 months. Dialyzers were reused up to 30 times to reduce the cost of HDF. All the patients were hemodynamically stable during both HDF and high-flux HD treatments. No febrile reactions were reported. The percentage reduction of ß2M during HDF was significantly higher when compared with high-flux HD (75 ±4% vs 51 ±7%, p < 0.001). After 14.2 ±7.1 months of HDF, the patients had significant reduction of both the pre-dialysis ß2M level (47.4 ±7.9 μg/mL vs 28.2 ±4.9 μg/mL, p < 0.01) and post-dialysis ß2M level (11.4 ±2.8 μg/mL vs 6.8 ±1.0 μg/mL, p < 0.01). eKt/V achieved by HDF was significantly higher than that achieved by high-flux HD (1.94 ±0.26 vs 1.75 ±0.23, p < 0.01). Those patients with dialysis arthropathy and carpal tunnel syndrome had decreased joint pain and hand numbness respectively after putting on HDF but symptoms recurred while on high-flux HD. There were no statistical significant differences in the percentage reduction of ß2M, ß2M clearance, urea clearance and eKt/V with dialyzer reuse, and no adverse patient reactions had been recorded.ConclusionOn-line HDF has been proven to be a safe and reliable treatment. The clearance of ß2M and urea are significantly increased by HDF when compared with high-flux HD, and the increase in clearance of ß2M is sustained throughout the HDF treatment period. Symptoms of dialysis-related amyloidosis are improved by HDF. Dialyzer reuse, which reduces the cost of HDF by 30%, is feasible and safe.     

Post‐Dilution Hemodiafiltration With a Heparin‐Grafted Polyacrylonitrile Membrane

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post‐dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty‐four patients from eight centers were included in the study and treated by means of post‐dilution on‐line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000‐unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low‐molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post‐dilution hemodiafiltration with reduced doses of LMWH.