Comparison of Solute Clearance, Hospitalization Rate, and Aortic Arch Calcification between Online Hemodiafiltration and High-Flux Hemodialysis: A 6-Year Observational Study.

BACKGROUND/AIMS: Studies on the long-term clinical benefits of hemodiafiltration (HDF) and high-flux hemodialysis (HFHD) are very limited. This study aimed to investigate the hospitalization rate and aortic arch calcification (AAC) of these two dialysis modalities over 6 years. METHODS: Participants who received regular HDF and HFHD in one hospital-facilitated hemodialysis center were prospectively enrolled after matching for age, sex, and diabetes between January 2009 and December 2014. Medical records were reviewed retrospectively on demographics, laboratory variables, calcified scores in aortic arch measured by chest radiography, and rates of hospital admission. Cox proportional hazard regression and linear regression were used to obtain the outcome results. RESULTS: The HDF and HFHD groups consisted of 108 and 102 participants, respectively. Levels of laboratory variables including small soluble solutes and Kt/V were not statistically different over the 6-year period between the HDF and HFHD groups. Calcified scores of the aortic arch increased over 6 years in both groups. The changes in the mean calcified scores were significant when compared between the two groups (0.44-1.82 in HFHD, 0.79-1.8 in HDF, respectively, p = 0.008). Hospitalization rates were 735 per 1,000 patients in the HDF group and 852 per 1,000 patients in the HFHD group, respectively. No significant difference was observed in frequency and days of hospitalization between HDF and HFHD. CONCLUSION: Hospitalization rates and AAC were observed to be equal for HDF and HFHD.

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.

Emerging clinical evidence on online hemodiafiltration: does volume of ultrafiltration matter?.

Online hemodiafiltration (OL-HDF), first described in 1985, is today a widely prescribed treatment modality for end-stage chronic kidney disease (CKD) patients. Other than in the United States, prescription of the treatment modality is widespread with a steady increase since its inception. Indeed, in Western Europe, more CKD patients receive OL-HDF than peritoneal dialysis, hitherto the second most prescribed therapy after conventional hemodialysis. The rise and success of OL-HDF can be attributed to diverse clinical advantages that have been documented over the last two decades. Numerous publications attest to the beneficial effects of OL-HDF in terms of removal of a broad spectrum of uremic toxin, anemia control, phosphate reduction, increased hemodynamic stability and blood pressure control and less dialysis-related amyloidosis, to mention just a few. Significantly, the improvement in these conditions is considered to contribute to improved patient outcomes. Despite the extended worldwide clinical experience, elaborate scientific validation of the principles of the therapy and technical innovations that facilitate its prescription, a point of contention is whether OL-HDF leads to a reduction of mortality rates. A number of observational and retrospective analyses have indicated a survival benefit, while prospective investigations involving small numbers of patients but nevertheless specifically addressing survival have further supplied evidence of improved survival with OL-HDF. The quest for large-scale, multicenter prospective randomized controlled trials examining patient survival led to the CONTRAST and the Turkish OL-HDF trials. Both trials have been concluded and published recently. In this chapter, we document and assess the key investigations that have examined the impact of OL-HDF on patient outcome and survival. Based on the findings of previous analyses and of the two recently concluded trials, it appears that the volume of convection appears to be decisive towards the survival benefit accredited to OL-HDF. We consider the implications of this new evidence.

New high-cutoff dialyzer allows improved middle molecule clearance without an increase in albumin loss: a clinical crossover comparison in extended dialysis.

BACKGROUND: Accumulation of middle molecules is thought to have adverse effects in patients with acute kidney injury (AKI). Elimination of middle molecules by non-convective means, i.e. hemodialysis, remains difficult. The aim of the study was to investigate the removal characteristics of a new high permeability membrane in AKI patients undergoing extended dialysis (ED). PATIENTS AND METHODS: We performed a prospective, crossover study comparing the EMiC2 dialyzer (1.8 m(2), FMC, Germany) and AV 1000S (1.8 m(2), FMC) in 11 critically ill patients with AKI. ß2-Microglobulin, cystatin c, creatinine, and urea were measured before and after 0.5, 5.0 and 10 h of ED. Serum reduction ratios, dialyzer clearances, and mass in the total collected dialysate were determined. RESULTS: Dialyzer clearance of ß2-microglobulin (EMiC2: 52 ± 1.7 ml/min, AV 1000S: 41.7 ± 1.5 ml/min, p = 0.0002) and cystatin c (EMiC2: 47.2 ± 1.2 ml/min, AV 1000S: 34.2 ± 2.3 ml/min, p < 0.0001) was markedly different, as was the reduction of serum levels of ß2-microglobulin (EMiC2: 54.3 ± 3.6%, AV 1000S: 39.1 ± 4.5%, p = 0.025) and cystatin c (EMiC2: 38.9 ± 2.6%, AV 1000S: 28.0 ± 3.9%, p = 0.043). Additionally, we observed a higher total amount of these substances in the collected dialysate. There was no significant difference in the total amount of albumin eliminated per treatment. CONCLUSION: The new EMiC2 dialyzer enhances removal of middle molecules without an increase in albumin loss. The clinical relevance of this finding needs to be determined.

Assessment of eptifibatide clearance by hemodialysis using an in vitro system.

BACKGROUND/AIMS: Eptifibatide is a parenteral glycoprotein IIb-IIIa inhibitor that prevents platelet aggregation. Although contraindicated in dialysis patients due to limited safety and dialysis data, eptifibatide is prescribed in this population and is associated with bleeding complications. This study was done to determine dialysis clearance (CL(D)) of eptifibatide using an in vitro system. METHODS: Three common dialyzers were tested. In vitro dialysis was performed at a dialysate flow rate of 500 ml/min, 'blood' flow rate (Q(B)) of 200 and 400 ml/min, and the minimal ultrafiltration rate. Eptifibatide CL(D) and fraction removed were calculated for each condition. RESULTS: CL(D) ranged from 122 to 225 ml/min and was not significantly different among the dialyzers tested. CL(D) was flow dependent with higher clearances observed at higher Q(B). The estimated fraction of eptifibatide removed was 73-83%. CONCLUSIONS: These data suggest that hemodialysis is an effective method to decrease the effects of eptifibatide in patients with impaired kidney function.

Effect of online hemodiafiltration on morbidity and mortality of chronic kidney disease patients.

Conventional diffusion-based dialysis modalities including high-flux hemodialysis (HD) are limited in their capacity to clear uremic toxins. Moreover they are associated with a relatively high incidence of morbidity and mortality. Online hemodiafiltration (ol-HDF) combining the use of a high-flux membrane dialyzer, ultrapure dialysis fluid and high convective fluid exchange is highly efficient with the lowest bioreactive profile in renal replacement therapy methods. Regular use of high-efficiency ol-HDF is associated with reduced morbidity (hypotension incidence, better blood pressure control, improved hemocompatibility, reduced inflammation profile, improved lipid profile, improved anemia correction, reduced incidence of beta2-microglobulin amyloidosis and hospitalization). More recently, several cohort studies have shown that high-efficiency ol-HDF is associated with a 35% reduced risk of mortality in an unselected dialysis population. ol-HDF has been proven to be a safe and very efficient renal replacement therapy. ol-HDF has come of age and should be considered now as the new standard for highly efficient renal replacement therapy.

Disinfection of dialysis monitors.

In recent years the concept of biocompatibility is not limited to the dialytic membranes, but has been substituted by a more general viewpoint where all the parameters of the dialytic treatment are taken into consideration: the interaction of blood-surfaces (the dialyzer in all its components and the hematic lines), the sterilization of all materials, the quality of the solutions utilized for dialysis and reinfusion. Numerous studies have shown that the inflammatory response in dialysis is the cause of many of the side effects of dialytic treatment itself both acute and chronic. Hypoxemia, 'first use' syndrome, hypotension, allergic-anaphylactic reactions (short-term side effects); microinflammation, malnutrition, accelerated arteriosclerosis, anemia, beta2 microglobulin amyloidosis, immunodeficiency, bone mass loss (long-term side effects), have all been reported. In this review, we will focus on the fluids utilized for hemodialysis (HD) and hemodiafiltration (HDF); we will describe the process of disinfection of the machines which produce the dialytic solutions.

Treatment of multiple organ failure through sepsis by surgery and blood purification.

For the treatment of multiple organ failure (MOF) through sepsis, we have commonly applied various blood purification modalities during the perioperative period. From January 1996 to December 2000, 33 patients with MOF through sepsis were admitted and operated on in the First Department of Surgery, Akita University School of Medicine, and 21 of these 33 patients were treated using various blood purification modalities during the perioperative period: endotoxin-adsorbing therapy using polymyxin B (PMX) in 17 patients, continuous hemofiltration (CHF)/continuous hemodiafiltration (CHDF) in 15 patients, and plasma exchange (PE) and CHDF in 3 patients. Of the outcome of these 33 patients with MOF through sepsis, 17 survived and 16 died (48% mortality). Of the 21 patients with MOF through sepsis treated by surgery and blood purification, 12 survived and 9 died (43% mortality). We evaluated APACHE II and the number of failed organs before operation. Amongst the group with 12 survivors and 9 deaths, Acute Physiology and Chronic Health Evaluation II (APACHE II) was 15 +/- 5, 23 +/- 2 and the number of failed organs was 2.7 +/- 0.7, 3.9 +/- 0.8, respectively. An increased APACHE II score and number of failed organs were significantly associated with mortality. As to the treatment of MOF through sepsis due to acute peritonitis, patients with APACHE II scores ranging from 15 to 20, and those with 2-3 failed organs seem to be the candidates for the application of blood purification during the perioperative period.

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.

[Safety controls in a new hemodiafiltration on line technique (PHF)]. / Controlli di sicurezza in una nuova tecnica di emodiafiltrazione on-line (PHF).

PURPOSE: On-line hemodiafiltration (HDF) is gaining popularity due to increasing evidence of clinical benefits. The purpose of this study was to test a new on-line technique paired hemodiafiltration (PHF). In addition, we evaluated the PHF system during in vitro contamination. METHODS: Five patients used the PHF technique over a 6-month period. We performed a disinfection protocol and tested for bacteria, endotoxin, halogenated carbons and metals in the feed water, and we tested for bacteria, endotoxins and fungi in the dialysate after different ultrafiltration stages. In vitro tests were performed using three bacterial concentrations of pseudomonas aeruginosa. Samples were analyzed from different sites throughout the entire on-line HDF circuit for bacteria endotoxins, fungus and the ability to stimulate whole blood production of tumor necrosis factor-alpha (TNF-alpha). RESULTS: The bacteriological control from the feeding machine water and at the entrance to the monitors had a bacterial level of <100 CFU/mL. No bacteria were detected in the dialysate and endotoxin levels were <0.03 EU/mL. In the in vitro contamination study, with the three bacterial concentrations tested at various points in the circuit, bacterial and fungi were below the level of detection and endotoxins were <0.03 UE/mL. The addition of dialysate samples taken after the 1st microfiltration stage, as well as after the 1st and 2nd ultrafiltration stage and incubated with whole blood were not associated with stimulated TNF-alpha production. CONCLUSIONS: PHF appeared to be a safe and feasible method for on-line HDF even in the unforeseen presence of the bacterial contamination of the feed water or in the water distribution system.

Effect of hemodiafiltration against radical stress in the course of blood purification.

The involvement of radical stress has been suggested as a cause for complications in patients on dialysis, such as arteriosclerosis, dialysis-related amyloidosis, etc. It has been reported that the increase in radical stress is not only seen in renal failure, but that its amplified effect is also seen in the process of blood purification. Our group has reported on the radical stress-reducing effect of HDF. We performed four types of blood purification (HD; on-line HDF; pre, on-line HDF; post, P/P HDF) in patients on maintenance dialysis using the polysulfone (APS) dialyzer. The change in radical related markers such as pentosidine (total, free) and CML (total, free), and the CTL/Cr ratio, and the hydroperoxide radicals were studied. In HDF (post, pre), the amplification rate of hydroperoxide radicals was significantly low, whereas the reduction rate of CTL/Cr ratio as index for hydroxy radicals was significantly higher in on-line HDF than in HD. Both the total CML and T-pentosidine increased in HD but showed a decrease in HDF. As HDF uses large amounts of replacement solution, the following effects can be expected: (a) suppression of the amplification of hydroperoxide radicals and suppression of the amplification of hydroxy radicals, and (b) suppression of fat oxidation by AGEs themselves. These antiradical stress effects are presumed to be exerted by effective removal of radical carrier protein, denatured protein, and complement protein in HDF, by dilution of radicals by massive use of replacement solution, and by the sequential reduction of the excitation and amplification effects.

Relationship between natriuretic peptides and residual diuresis during continuous hemodiafiltration.

BACKGROUND: The reasons for the decrease or increase of urine output following the start of continuous venovenous hemodiafiltration (CVVHDF) have not yet been explained sufficiently. The renoprotective properties of natriuretic peptides were described. METHODS: The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 23 mechanically ventilated patients before and during the first 48 h of CVVHDF. Samples were drawn both from the ports proximal and distal to the filter. The results were compared between the group where daily diuresis (Vu) remained low or decreased and the group where diuresis increased to the level of 1.5 ml x kg(-1) x h(-1) or higher after 48 h of treatment. Left ventricular dysfunction (LVD) was defined as LV ejection fraction below 40%. A control group consisted of 10 patients exposed to abdominal surgery. RESULTS: The average AVdiff (%) of ANP and BNP on filter were insignificant. Patients with increasing diuresis (n = 12) had significantly lower levels of both ANP (p < 0.001) and BNP (p < 0.005) than the patients with decreasing diuresis (n = 11). Significant correlations were revealed for ANP and Vu (p < 0.01) and for BNP and Vu (p < 0.05). The levels of both peptides were grossly elevated in comparison to controls and were predictive of survival. The differences between cardiac and non-cardiac patients were significant both for ANP and for BNP. CONCLUSIONS: The elimination of ANP and BNP by the CVVHDF is negligible. The levels of natriuretic peptides are inversely related to Vu and predict survival. ANP and BNP levels correlate with left ventricular function even during acute renal failure and CVVHDF.