Clinical evidence on haemodiafiltration.

Haemodiafiltration (HDF) combines diffusive and convective solute removal in a single treatment session. HDF provides a greater removal of higher molecular weight uraemic retention solutes than conventional high-flux haemodialysis (HD). Recently completed randomized clinical trials suggest better patient survival with online HDF. The treatment is mainly used in Europe and Japan. This review gives a brief overview of the presently available evidence of the effects of HDF on clinical end points, it speculates on possible mechanisms of a beneficial effect of HDF as compared with standard HD and ends with some perspectives for the future.

Effect of high fiber density ratio polysulfone dialyzer on protein removal.

BACKGROUND/AIMS: A dialyzer (APS-EX) with a higher hollow fiber density ratio was manufactured using the highest performance polysulfone hollow fiber from Asahi-Kasei Medical. METHODS: We compared the performance of this device in comparison with hemodialysis (HD; APS-S) and hemodiafiltration (HDF) conditions (APS-S, 10 l post-HDF) to evaluate its merit as an internal filtration-enhanced dialyzer. RESULTS: With low molecular weight proteins, APS-EX had a reduction ratio of 74.3% for beta(2)-microglobulin (beta(2)-MG), and 31.0% for alpha(1)-MG. APS-EX had a significant higher removal amount of alpha(1)-MG compared to APS-S (HDF). Significant differences were seen in albumin loss, 4.0 g for APS-EX, 3.0 g for APS-S (HDF), and 0.9 g for APS-S (HD). Using HD mode, APS-EX demonstrated a performance which was more than equivalent to approximately 10 l post-HDF. CONCLUSIONS: The results suggested the possibility that HD equivalent to HDF can be performed safely with the ultrapure dialysate when using APS-EX with internal filtration.

Biocompatibility of Hemodiafilters.

BACKGROUND: Biocompatibility and the efficiency of solute removal are important considerations in blood purification therapy. Improvement of biocompatibility is expected to lead to the prevention of dialysis-related complications (e.g. amyloidosis, arteriosclerosis, and malnutrition) and to the delay of disease progression by alleviating microinflammation. SUMMARY: The biocompatibility of dialyzers is greatly influenced by the interaction between blood and the treatment materials, in which the chemical and physical characteristics of membrane materials play important roles. In hemodiafiltration (HDF), treatment characteristics such as dilution modes are also considered to greatly affect this interaction between blood and materials. Studies have reported that the levels of C-reactive protein are decreased in patients receiving HDF. Thus, the improvement of biocompatibility is an important factor in HDF. Key Messages: To improve the biocompatibility of HDF, it is essential to improve the biocompatibility of hemodiafilters. This article outlines the importance of biocompatibility and related factors in HDF.

A New Poly(Methyl Methacrylate) Membrane Dialyzer, NF, with Adsorptive and Antithrombotic Properties.

BACKGROUND: Poly(methyl methacrylate) (PMMA) membranes adsorb several kinds of proteins and can remove high-molecular-weight proteins, including uremic toxins, which are not removed efficiently by hemodialysis or hemodiafiltration. However, the antithrombogenicity of PMMA membranes is insufficient due to their adsorptive properties. SUMMARY: Coagulation during hemodialysis occurs because proteins that are adsorbed to the PMMA membrane undergo structural changes and are recognized by platelets, which are then activated by adhesion to the membrane surface. In developing a new PMMA membrane dialyzer, NF, we intended to inhibit platelet adhesion to the membrane surface by suppressing the structural change in the proteins adsorbed on the membrane. In addition, we give examples of clinical trials of the NF in Japan and describe its advantages. Key Message: PMMA membrane dialyzers have been used for 40 years. The PMMA dialyzer NF can suppress the adhesion of platelets to the membrane while maintaining protein adsorption.

A comparison of solute clearance during continuous hemofiltration, hemodiafiltration, and hemodialysis using a polysulfone hemofilter.

The clearance of urea, creatinine, amino acids, vancomycin, and phenytoin was measured in vivo in a small animal model during continuous venovenous (CVV) hemofiltration, CVV hemodiafiltration, and CVV hemodialysis using a 0.25 m2 polysulfone hemofilter. Six domestic piglets (weighing 6-11.8 kg) each received 1 hr of all three techniques in random order. Blood flow was 50 ml/min. During CVV hemofiltration, filtrate production was 500 ml/hr and dialysate flow was zero. During CVV hemodiafiltration, filtrate production was 250 ml/hr and dialysate flow was 250 ml/hr. During CVV hemodialysis, net filtrate production was zero and dialysate flow was 500 ml/hr. The ratio of concentration of solute in filter effluent to concentration in whole plasma was derived for each solute during each of the three techniques. Mean (SD) effluent:plasma ratio for urea during CVV hemofiltration was 0.957 (0.038), CVV hemodiafiltration 0.876 (0.109), and CVV hemodialysis 0.754 (0.123); creatinine 0.942 (0.05), 0.934 (0.056), and 0.814 (0.057); amino acids 0.996 (0.344), 0.904 (0.196), and 0.778 (0.18). For small unbound solutes, there is a decrease in clearance of 6% from CVV hemofiltration to CVV hemodiafiltration and a further decrease of 14% from hemodiafiltration to hemodialysis. The effluent:plasma ratio for vancomycin during CVV hemofiltration was 0.739 (0.082), CVV hemodiafiltration 0.643(0.063), and CVV hemodialysis 0.509 (0.081), corresponding to a decrease of 30% from CVV hemofiltration to CVV hemodialysis. The effluent:plasma ratio for phenytoin was 0.302 (0.028) during CVV hemofiltration and was not significantly different during CVV hemodiafiltration or CVV hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of solute and fluid removal in hemodiafiltration.

BACKGROUND: Prescribing therapeutic conditions for online predilution hemodiafiltration (HDF) with fixed total dialysate flow rate Q(Dtotal) is not straightforward, since the increase in the substitution fl ow rate Q(S) is compensated by the decrease in the net dialysate flow rate Q(Dnet). METHODS: Clearances of various solutes under online predilution HDF were clinically evaluated with fixed Q(Dtotal) (= 520 ml/min) divided into Q(Dnet) and Q(S). Three polysulfone membrane dialyzers and 5 polyester polymer alloy membrane dialyzers were chosen to measure sieving coefficients (SC) for albumin in vitro at 37 degrees C to predict when the albumin loss is greatest during clinical treatment. RESULTS: Clearances of small solutes such as urea and creatinine increased in vivo with the increase in blood flow. These values, however, slightly but steadily decreased with the increase in Q(S) because the increase in Q(S) decreased Q(Dnet). Clearances of beta2-microglobulin and alpha1-microglobuin increased with the increase in Q(S) and decreased with the increase in Q(Dnet), because clearances of larger solutes were more strongly dependent on ultrafiltration than on diffusion. The SC for albumin in vitro showed a peak at the beginning of the experiment in those membranes with large proportions of polyvinylpyrroridone (PVP), which may lead to large amounts of albumin loss at the beginning of the treatment. CONCLUSIONS: Dialysis prescription in online predilution HDF in terms of maximizing clearance for the solute of interest may be different for each target solute. The amount of albumin loss may be closely related to the amount of PVP included in the membrane.

Double-chamber on-line hemodiafiltration: a novel technique with intra-treatment monitoring of dialysate ultrafilter integrity.

On-line hemodiafiltration is a technique that relies on the re-injection of pyrogen-free substitution fluid obtained by cold filtration of dialysate. Therefore, safety of this treatment modality depends on the quality of dialysate and, mainly, on the integrity of the ultrafilter(s) employed. Double-chamber on-line hemodiafiltration is a new technique where re-infusion takes place inside the dialyser by means of dialysate backfiltration. The peculiar geometry of the dialyser allows intra-treatment assessment of its fibre integrity. In this paper, we tested feasibility and safety of this new modality of on-line treatment. The extracorporeal blood and infusate pressure values resulted well inside the safety range. Blood urea clearances and beta(2) removal were consistent with the figures usually found in standard hemodiafiltration. Whole blood production of cytokines was similar when blood was exposed to saline or infusate, both values being comparable to the spontaneous whole blood cytokine release. The on-line dialyser fibre integrity check showed a great sensitivity even for minimal dialyser damage. We conclude that double-chamber on-line hemodiafiltration is a feasible and safe procedure. Our preliminary results encourage the undertaking of multicentre, prospective, randomised studies.

On-line hemodiafiltration: technique and therapy.

On-line hemodiafiltration (HDF) provides the largest amount of blood purification over a wide molecular weight spectrum achievable with present renal replacement therapies. When used with state of the art dialysis membranes and treatment systems, the biocompatibility of on-line HDF is as high as can presently be defined. From an economic perspective, the added cost of the ultrafilters used to prepare the substitution solution is balanced by the therapeutic benefits of HDF. For optimal HDF, the ultrafiltration rate must be maximized with respect to the blood flow rate. In on-line HDF systems, the excess volume ultrafiltered, approximately 20 to 30 liters per treatment, is automatically replaced, preferably in postdilution mode, by a substitution solution that is continuously generated by stepwise ultrafiltration of dialysate. When properly prepared, this fluid fulfills the quality demands of commercially available infusion solutions; that is, it can be referred to as sterile and pyrogen-free. The most important factors in preparing substitution solution are the quality of the water, of the concentrates, of the ultrafilters, and the microbiological status of the entire flow path. The clinical safety of substitution solution prepared on-line has been documented by long-term users of on-line systems. Results from clinical studies with on-line HDF confirm the overall increased clearance of solutes in relation to high-flux dialysis using the same membrane.

Modulation of polymorphonuclear leukocyte apoptosis in the critically ill by removal of cytokines with continuous hemodiafiltration.

Delay of polymorphonuclear leukocyte (PMN) apoptosis caused by hypercytokinemia is considered to be a potential cause of tissue damage and resultant organ failure. We evaluated whether continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF), which can remove cytokines in the circulating blood, can modulate apoptosis in peripheral blood neutrophils and thereby reduce tissue damage and organ dysfunction in 25 critically ill patients. Following the completion of a 3-day PMMA-CHDF session, serum cytokine levels were significantly decreased and the percentage of apoptotic PMNs was significantly increased. A significant correlation was observed between the PMMA-CHDF-induced increase in the percentage of apoptotic PMNs and the degree of decrease in the serum interleukin-6 level. A significant correlation was also found between the increase in the percentage of apoptotic PMNs and improvement in sequential organ failure assessment score following PMMA-CHDF. These results suggest that PMMA-CHDF in critically ill patients with hypercytokinemia and concomitant delay in apoptosis of PMNs can alleviate the delay of PMN apoptosis through the removal of serum cytokines and thus may result in avoidance of organ dysfunction.

Favorable effect of new artificial liver support on survival of patients with fulminant hepatic failure.

The two most serious symptoms of fulminant hepatic failure are bleeding and hepatic coma. To overcome these problems, we developed an artificial liver support system comprising a combination of plasma exchange and hemodiafiltration using a high performance membrane. We treated 67 patients with fulminant hepatic failure. Of these, 65 patients (97.0%) regained normal consciousness, and 55 patients (80.9%) were kept alert as long as we continued to apply this system. All 7 patients (100%) with fulminant hepatitis caused by hepatitis A virus infection and 9 of 12 patients (75%) with fulminant hepatitis caused by acute hepatitis B (HB) virus infection survived. In addition, 7 of 15 HB virus carriers (46.7%) who developed fulminant hepatitis and 11 of 29 patients (37.9%) with fulminant hepatitis caused by non-A, non-B hepatitis viruses survived. The overall survival rate was 37 of 67 patients (55.2%). Our artificial liver support system allows as high a survival rate as liver transplantation.

Intradialytic glucose infusion increases polysulphone membrane permeability and post-dilutional haemodiafiltration performances.

INTRODUCTION: During real-time monitoring of the ultrafiltration coefficient (Kuf) in haemodiafiltration (HDF), it was noticed that the ultrafiltration performance of polysulphone membrane dialysers increased when hypertonic glucose (D50%) was administered through the venous blood return. METHODS: This observation was explored in six non-diabetic chronic dialysis patients during 48 HDF sessions using 1.8 m(2) polysulphone membrane dialysers. In all six patients, 24 sessions were performed with glucose supplementation (as a continuous D50% (500 g/l) infusion at 40 ml/h) and 24 sessions without supplementation. RESULTS: Glucose supplementation led to a marked increase in Kuf from 22.8+/-2.2 (without D50%, n=24) to 32. 1+/-3.9 ml/h/mmHg (with D50%, n=24) (P<0.0001). An increase in percentage reduction ratios for urea and creatinine were also consistently observed during the sessions with glucose administration (from respective mean values of 75+/-5 and 68+/-4% to 79+/-4 and 74+/-10%). Mean double-pool Kt/V, calculated from serum urea concentrations, rose from 1.65+/-0.24 (n=24) to 1.86+/-0.24 (n=24) (P<0.005). Similar results were observed in a subgroup of 18 HDF sessions (nine with glucose and nine without) monitored with an on-line urea sensor of spent dialysate. No detrimental effects were induced at any time. CONCLUSIONS: We conclude that intravenous glucose administration during high-flux HDF using polysulphone membranes increases significantly both ultrafiltration capacity and dialysis dose delivery.