Anaphylactoid reaction during hemodiafiltration on AN69 membrane in a patient with atypical hemolytic uremic syndrome: A pediatric case report

Reactions associated with hemodiafiltration can be life threatening if not recognized early in the course of dialysis. AN69 (acrylonitrile and sodium methallyl sulfonate copolymer) membrane-associated reactions during hemodialysis have been documented in adult patients receiving angiotensin converting enzyme inhibitors, which are thought to be triggered by the negative charge of the AN69 membrane. Here, we present a 5-month-old girl requiring continuous renal replacement therapy (CRRT) for acute kidney injury secondary to atypical hemolytic uremic syndrome who experienced acute cyanosis, angioedema, tachycardia, and impaired circulation during CRRT. After switching to a different type of hemofiltration membrane, her clinical findings improved and she was able to tolerate hemodialysis. We concluded that she had experienced an anaphylactoid reaction to the AN69 membrane. To our knowledge, this case is the first pediatric case report of AN69 membrane-associated anaphylactoid reaction.     

Tandem dialyzers with dual monitors to meet Kt/V targets

Purpose:  This study evaluated improvements in dialyzer reuse parameters and clinical outcomes associated with a CQI project in a hospital‐based dialysis center in which high flux polysulfone dialyzers were replaced with high flux Polyflux® dialyzers (GAMBRO® Renal Products). Methods:  Dialyzers were reprocessed using a Renatron® II Dialyzer Reprocessing System in conjunction with Renalin® sterilant (Minntech Corp.). Renalog® RM software was used to track dialyzer reprocessing rates and failures. Reasons for dialyzer failure included inadequate dialyzer volume; excess pressure; appearance; clotting during use; and maximum number of uses reached. The average number of dialyzer reuses with polysulfone dialyzers between January and June 2002 were compared to that achieved with Polyflux® dialyzers for the same periods in 2003 and 2004. Analysis periods were separated to avoid the impact of dialyzer transition on clinical parameters. Achievement of URR goals during these same periods was likewise compared. Results:  Transition from polysulfone to Polyflux® dialyzers was associated with a >40% increase in average number of reuses between 2002 and 2003 and a >63% increase comparing the 2002 and 2004 periods. During the 2002 analysis period with polysulfone dialyzers the target URR of 65% was achieved in approximately 75% of hemodialysis patients; this increased to nearly 95% with Polyflux® dialyzers in both the 2003 and 2004 periods, despite more reprocessing of these dialyzers. Conclusions:  These results demonstrate an improvement in both reuse efficiency and clinical outcomes associated with Polyflux dialyzers. Identifying clinical products through CQI studies that provide an economic and clinical advantage plays an important role in the success of hospital‐based hemodialysis.     

The role of dialyzer membrane flux in bio-incompatibility

Dialyzer membrane flux is currently defined according to beta(2)-microglobulin (a middle molecule) clearance. Traditionally, high flux membranes were synthetic, and caused less inflammatory reaction in the extracorporeal circuit, compared with standard low-flux cuprophan bio-incompatible dialyzers. Initial reports suggested improved patient outcomes in acute renal failure when noncuprophan dialyzer membranes were used. However, over time these positive observations have not been substantiated. As the price differential between these dialyzer membrane types has become marginal, more high-flux dialyzers are now used in routine clinical practice. Two multicenter trials have recently reported a survival advantage for high-flux dialyzers. Whether this is directly consequent upon the choice of dialyzer membrane, or related to improvements in dialysate water quality, or changes in other clinical practices remains to be determined.     

On‐line Haemodiafiltration in the Management of Acute Renal Failure

Dialysis adequacy targets are frequently difficult to achieve in large hemodialysis patients. Dual dialyzers can be used to improve clearance. It is unknown whether series or parallel configurations are superior. Objective: to improve urea clearance in large patients using parallel and series dual dialyzers. Patients and Methods: Eighteen large hemodialysis patients (mean 92.4 kg) were enrolled in a randomized, crossover trial to directly compare dual dialyzers in parallel and series configurations. Treatments times, blood flow rates, and dialysate flow rates were kept constant. Results: Compared to single dialyzers, parallel dual dialyzers increased the spKt/V from 1.25 +/− 0.22 to 1.43 +/− 0.29 (p < 0.003). Series dual dialyzers improved the spKt/V to 1.46 +/− 0.26 (p < 0.0003 compared to single dialyzer). The Kt/V and URR of dual dialyzers in parallel were not significantly different from dual dialyzers in series. Half of the subjects failed to meet the NKF‐K/DOQI recommended adequacy target of spKt/V urea >/= 1.2 using a single dialyzer. With the use of dual dialyzers 83% of subjects achieved this adequacy target. Serum levels of 'middle molecule,' beta‐2 microgobulin, were reduced 34% after two months of dual dialyzer therapy. Cost analysis estimates annual net savings of $1260 with dual dialyzer therapy, primarily from projected savings in inpatient expenses. Conclusions: In large hemodialysis patients, our study demonstrates that dual dialyzers in parallel and series are equally effective in improving urea clearance without prolonging dialysis treatment times.     

Does an alteration of dialyzer design and geometry affect biocompatibility parameters?

The aim of the study was to assess the biocompatibility profile of a newly developed high-flux polysulfone dialyzer type (FX-class dialyzer). The new class of dialyzers incorporates a number of novel design features (including a new membrane) that have been developed specifically in order to enhance the removal of small- and middle-size molecules. The new FX dialyzer series was compared with the classical routinely used high-flux polysulfone F series of dialyzers. In an open prospective, randomized, crossover clinical study, concentrations of the C5a complement component, and leukocyte count in blood and various thrombogenicity parameters were evaluated before, and at 15 and 60 min of hemodialysis at both dialyzer inlet and outlet in 9 long-term hemodialysis patients using the FX60S dialyzers and, after crossover, the classical F60S, while in another 9 patients, the evaluation was made with the dialyzers used in reverse order. The comparison of dialyzers based on evaluation of the group including all procedures with the FX60S and the group including procedures with the F60S did not reveal significant differences in platelet count, activated partial thromboplastin times, plasma heparin levels, platelet factor-4, D-dimer, C5a, and leukocyte count at any point of the collecting period. Both dialyzer types showed a significant increase in the plasma levels of the thrombin-antithrombin III complexes; however, the measured levels were only slightly elevated compared with the upper end of the normal range. Biocompatibility parameters reflecting the behavior of platelets, fibrinolysis, complement activation, and leukopenia do not differ during dialysis with either the FX60S or the F60S despite their large differences in design and geometry features. Although coagulation activation, as evaluated by one of the parameters used, was slightly higher with the FX60S, it was still within the range seen with other highly biocompatible dialyzers and therefore is not indicative of any appreciable activation of the coagulation system. Thus, the incorporation of various performance-enhancing design features into the new FX class of dialyzers does not result in a deterioration of their biocompatibility profile, which is comparable to that of the classical F series of dialyzers.     

Clearance of small molecules in different dialyzer flow configurations

To overcome problems of insufficient clearance, multiple dialyzers may be placed in series or in parallel. The present study aimed to investigate in vitro the overall clearance of small molecules in different dialyzer configurations in which mutual flow directions were changed. Single pass tests were performed with low flux Fresenius F6HPS dialyzers placed in series (12 tests), in parallel (6) and in single use (2). As blood substitute, either high concentrated (45 mS) bicarbonate dialysate (AB solution – MW20‐180) or a trisodiumphosphate (Na₃PO₄– MW395) concentration (30 mS) was used. Standard blood and dialysate flows of 250 and 500 mL/min, respectively, were applied. Furthermore, clearance was derived from conductivity measurements in the inlet and outlet bloodline, correcting for the overall ultrafiltration rate of 0.5 L/h (AB) and 0.1 L/h (Na₃PO₄). Compared to the standard setup using a single dialyzer with counter current flows, clearance increases by 3 to 8%(AB) and by 15 to 18%(Na₃PO₄) using two dialyzers in parallel and in series, respectively. With co‐current flows in a serial dialyzer set up, clearance increases by 16%(AB) and 22%(Na₃PO₄) compared to the single dialyzer use. Changing subsequently the counter current flows to co‐current in one and both dialyzers in series, the overall clearance decreases by 2 to 9%, respectively, for the AB solution, and by 8 to 15% for the Na₃PO₄ concentration. With respect to the parallel dialyzer setup, a split dialysate flow (250 mL/min in each dialyzer) counter current to the blood flow, increases the clearance by 4 and 12%, respectively. In conclusion, overall clearance is most ameliorated using two dialyzers in series with counter current flows.     

Delayed Dialyzer Reprocessing for Home Hemodialysis

Although dialyzer reuse for home hemodialysis (done by patients at home) has been in practice since the 1960s, it is now almost completely abandoned. The need for dialyzer reuse resurfaced with the renewed interest in daily/nightly forms of home hemodialysis and the associated increase in operating costs. We describe a method of dialyzer reuse based on reprocessing of dialyzers at the center, after they had been stored in a refrigerator at home for 1 week by the patient. Transportation of the dialyzers by either the patient or a transportation service was acceptable to the patients. Despite the lower number of reuses, possibly related to the delayed processing, dialyzer reuse in this setting provided significant financial benefits. Experience with this process for 3 years has not disclosed any negative effects after the initial logistical issues related to dialyzer transportation were resolved. In summary, weekly dialyzer reprocessing at the center provides a solution to the need for dialyzer reuse for the home hemodialysis patient.     

Dialysis‐associated allergic reactions during continuous renal replacement therapy and hemodialysis: A case report

Dialyzer reactions are long‐appreciated complications of dialysis. Despite advances in dialysis machines and membranes, these life‐threatening reactions still occur. It is imperative to recognize potential dialyzer reactions when assessing adverse dialysis events as reexposure to dialytic treatments could be life threatening. We present the case of a 72‐year old woman with dialysis‐requiring anuric acute kidney injury who experienced acute hypotension and cardiopulmonary arrest during both continuous renal replacement therapy and a subsequent hemodialysis treatment. We concluded that she had an anaphylactic reaction to an unidentified component of the dialysis equipment. Identification, work up, treatment, and reporting of dialyzer reactions are discussed in the context of this case.     

Establishing a Home Nocturnal Hemodialysis Program: "Starting From Scratch"

Several types of dialyzers with enhanced internal filtration have been introduced in order to increase solute clearance, especially in relatively larger molecular solutes. In these dialyzers, enhanced internal filtration increased convective transport of the solute in addition to diffusive transport. The internal filtration flow rate (Q_IF) has not, however, been measured in clinical situations, because none of monitoring techniques can measure this value. Herein, the Q_IF value was estimated during an experimental and an analytical study. Namely, we measured blood flow velocity in a cross-sectional plane of the dialyzer by pulse Doppler ultrasonography. An in vitro study with bovine blood was carried out to determine the local blood flow velocity profile with a newly designed probe slider that enables parallel movement of the probe along the dialyzer. Furthermore, an analytical model was newly introduced to calculate changes in flow rate and pressure of blood and dialysate streams and solute concentrations along the dialyzer. The Q_IF value could be estimated by a simulation analysis to the experimental data using the analytical model.     

Flow distribution analysis by helical scanning in polysulfone hemodialyzers: effects of fiber structure and design on flow patterns and solute clearances

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, as this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different fiber bundle configurations on blood and dialysate flow distribution and urea clearances. The Optiflux 200 NR hemodialyzer was studied and the standard F 80 A hemodialyzer was used as a control for the study. Six dialyzers of each type were studied in vitro in the radiology department utilizing a new generation of helical computed tomography (CT) scan following contrast medium injection into the blood and dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer was undertaken to detect flow distribution, average and peak velocities, and calculate wall shear rates. Six patients were dialyzed with 2 different dialyzers in random consecutive sequence. In these patients, 2 consecutive dialyses were carried out with identical operational parameters (Qb = 300 mL/min, Qd = 500 mL/min). In each session, blood and dialysate side urea clearances were measured at 30 and 150 min of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with a new bundle configuration. Significantly increased urea clearances (p < 0.001) were seen with the Optiflux dialyzer compared with the standard dialyzer. In conclusion, more homogeneous dialysate blood and dialysate flow distribution and improved small solute clearances can be achieved by modifying the configuration of the filter bundle. These effects are achieved probably as a result of reduced blood to dialysate mismatch with reduction of flow channeling. The used radiological technique allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.     

Impact of flow and surface area on middle molecule clearance

Urea is still clinically applied as standard marker to quantify dialysis adequacy. The removal of middle molecules has however been proven in some studies to have a long‐term effect on mortality. Therefore, the present study is aimed at investigating the impact of blood and dialysate flow, and membrane surface area on middle molecule removal in low flux Fresenius F6HPS dialyzers. Blood and dialysate flows were varied within the clinical range of 300–500 mL/min and 500–800 mL/min, respectively, while ultrafiltration rate was kept constant at 0.1 L/h. Single pass tests were performed in vitro in a single dialyzer (3 tests) and in serially (5 tests) and parallel (3 tests) connected dialyzers. The blood substitution fluid consisted of bicarbonate dialysate in which radioactive labeled vitamin B12 (MW1355) was dissolved. Middle molecule concentrations of samples taken at the inlet and outlet blood line were derived from radioactivity measurements and were applied to calculate the dialyzer clearance as well as the reduction ratio. For the latter, the surrogate middle molecule vitamin B₁₂ was assumed as distributed according to a two‐pool kinetic model. Adding a second dialyzer in series or parallel ameliorates significantly overall dialyzer clearance and reduction ratio, except for the highest applied blood flow rate of 500 mL/min. Better solute removal is also obtained with higher dialysate flows, while the use of higher blood flows seemed only advantageous when using a single dialyzer. Analysis of the ultrafiltration profiles in the different configurations illustrated that enhancing the internal filtration rate ameliorates the convective transport of middle molecules. In conclusion, adequate solute removal results from a number of interactions, as there are, blood and dialysate flow rates, membrane surface area, filtration profile, and concentration profiles in the blood and dialysate compartment.     

Development of a high performance parallel-plate hemodialyzer

Early dialyzer development work had shown that a membrane support consisting of a square array of pyramids with a spatial density of 164/in² reduced fluid film resistances to 39 per cent of the total resistance to diffusion of chloride ion with a corresponding increase in dialyzer efficiency of 50 per cent. Subsequent experiments with small tests cells containing pyramidal membrane supports with densities of 256 and 576/in² have shown that even further reductions in fluid film resistance could be attained without adversely affecting other parameters in the dialyzer-patient system. These data have been used to calculate the dimensions of a dialyzer with a chloride clearance of 150 cc/min at 200 cc/min blood flow and 500 cc/min dialysate flow. In vitro performance of dialyzers fabricated to these dimensions have met design objectives. Clinical testing has shown comparable in vivo clearance rates of 126 cc/min for BUN and 102 cc/min for creatinine and the potential for ‘single-shift’ dialysis with a parallel-plate dialyzer.     

What is good about PD + HD combined therapy

It is known that β(2) -microglobulin (β(2) -MG) concentration in peritoneal dialysis (PD) patients is inversely correlated to the residual renal function (RRF). With decreasing RRF, some PD patients may necessarily be treated with hemodialysis (HD) once a week, not only for removing excess water and small solutes, but also for removing much larger solutes such as β(2) -MG. In this study, a kinetic model allowed us to show what is good about PD + HD combined therapy in long-term PD patients. A mathematical model was established based on a classic compartment theory for clinical use. Model validations were made by comparing calculated results with clinical data in order to specify what was good about PD + HD combined therapy (5-day PD?+?1-HD/week). Time-averaged concentration (TAC) for urea and creatinine decreased by 20% on the average by introducing PD+HD combined therapy no matter which dialyzers were used. TAC for β(2) -MG in PD+HD combined therapy, however, was strongly dependent upon the dialyzer clearance, and when a low flux dialyzer (clearance for β(2) -MG?=?10?mL/min under Q(B) =?200, Q(D) =?500?mL/min) was used, pre-dialysis β(2) -MG concentration may increase. Use of super high-flux dialyzers (clearance for β(2) -MG?=?60?mL/min under the same conditions) should greatly reduce the β(2) -MG concentration from 30 to 8?mg/L in 4-hr treatment. Then, when PD+HD combined therapy is introduced to a PD patient with diminishing RRF, use of super high-flux dialyzers may be strongly recommended in order not to increase concentrations of pre-dialysis β(2) -MG and/or even greater solutes. Use of super high-flux dialyzers is a key to the success of PD+HD combined therapy that could prevent concentrations of large solutes from increasing.     

Can dialyzer membrane selection affect outcomes in patients with acute kidney injury requiring dialysis?

The choice of dialyzer membrane may potentially affect not only solute clearances but also blood-dialyzer interactions. Although on one hand alteration of the dialyzer surface or pore size to increase inflammatory mediator loss may potentially be beneficial for patients with acute kidney injury (AKI), dialyzer membrane interactions, which precipitate intradialytic hypotension, may worsen AKI. Several years ago cellulosic membrane dialyzers were shown to reduce both patient survival and renal recovery in patients with AKI. This review looks at the earlier studies of dialyzer membrane choice and outcomes in AKI, besides discussing the newer developments in membrane technology for patients with AKI.     

Comparison of urea clearance in low‐efficiency low‐flux vs. high‐efficiency high‐flux dialyzer membrane with reduced blood and dialysate flow: An in vitro analysis

Rapid removal of small molecules during hemodialysis places an acutely ill patient with kidney failure at an increased risk of hemodynamic instability and for dialysis disequilibrium syndrome. The use of high‐flux, high‐efficiency (HEF) dialyzers may increase this risk despite reductions in blood and dialysate flow. We performed in vitro experiments to compare urea clearance at low dialysate flow and various blood flows using a low‐efficiency low‐flux (LEF) and a HEF membrane. Compared to LEF, there was a significant increase in the clearance of urea at all blood flows with the HEF (all P values < 0.005). HEF dialyzer (F180NR) had higher urea clearance at a blood flow of 150 mL/min than LEF dialyzer (F5) at blood flow of 300 mL/min (144.1 ± 0.99 vs. 130.1 ± 0.001 mL/min for F180 vs. F5, respectively, P < 0.002). Our data suggest that use of HEF dialyzer are not as safe as LEF in high‐risk acute dialysis patients since these are associated with more rapid removal of urea despite reduction in blood and dialysate flow as compared to LEF.     

Estimation of backfiltration flow rate in commercially available high flux dialyzers: Importance of water purification system for dialysate

Several types of high flux dialyzers were developed and introduced for clinical applications to improve solute removal efficiency. In these dialyzers, internal filtration/backfiltration (IF/BF) is induced by pressure drop of blood and dialysate flow in a countercurrent manner under less net filtration. Higher IF/BF flow rate increased convective transport of the solute in addition to diffusive transport. In previously published papers, we reported the effects of IF on solute removal efficiency of the dialyzer during an analytical and an experimental study and the measurement of the internal filtration flow rate (Q_IF) by Doppler ultrasonography. Average blood flow rate (QB_av) at a cross‐sectional plane was measured by pulse Doppler and the longitudinal QB_av profile along the dialyzer was obtained using a probe slider that can move the probe in parallel along the dialyzer. This is a suitable method for a bedside monitoring of the IF/BF flow rate of dialyzers because it is noninvasive to the patient and produces reliable data with higher reproducibility. Internal backfiltration flow rate (Q_BF) in six types of commercially available high flux dialyzers, having a higher 50 ml/min of β2‐microglobulin clearance (CL‐β2 m), were examined by Doppler ultrasonography under 10 ml/min/m² of net filtration flow rate. As a result, a wide range of Q_BF value, 12.1–28.4 ml/min, was obtained among those dialyzers. It means a fair amount of BF, 2.9–6.8 liter per session, occurs in a typical hemodialysis treatment. Strict management of dialysate purification is required for a dialyzer with a relatively larger BF. On the other hand, no correlation between the CL‐β2 m value and the Q_BF value was seen because the CL‐β2 m value depends on not only the IF/BF flow rate but also diffusive property of the membrane. The BF flow rate in every dialyzer should be examined to avoid suffering from the invasion of endotoxin and its fragment for safety.     

Middle molecule removal in low-flux polysulfone dialyzers: impact of flows and surface area on whole-body and dialyzer clearances

Some studies found that the removal of middle molecules has a long-term effect on mortality and, even more, is enhanced by high-flux dialysis. In order to enhance middle molecule removal in a low-flux dialyzer, the present study aimed at investigating the combined impact of dialyzer flows and membrane surface area. Blood and dialysate flows were varied within the clinical range 300-500 and 500-800 mL/min, respectively, while the ultrafiltration rate was kept constant at 0.1 L/hr. Single-pass tests were performed in vitro in a single Fresenius F6HPS dialyzer (3 tests) and serially (5 tests) and parallel (3 tests) connected dialyzers. The blood substitution fluid consisted of dialysis fluid in which radioactive-labeled vitamin B12 (molecular weight 1355 Da) was dissolved. Dialyzer clearance as well as whole-body clearance was calculated from radioactivity concentrations of samples taken from the inlet and outlet bloodline. Adding a second dialyzer in series or parallel ameliorated the overall dialyzer and whole-body clearance significantly, except for the highest applied blood flows of 500 mL/min. Better solute removal was also obtained with higher dialysate flows, while the use of higher blood flows seemed advantageous only when using a single dialyzer. Analysis of the ultrafiltration profiles in the different configurations illustrated that enhancing the internal filtration rate ameliorates convective transport of middle molecules. Adequate solute removal results from a number of interactions, as there are blood and dialysate flows, membrane surface area, filtration profile and concentration profiles in the blood and dialysate compartment.     

Biocompatibility of heparin-grafted hemodialysis membranes: impact on monocyte chemoattractant protein-1 circulating level and oxidative status

This prospective observational study aimed at evaluating efficacy and biocompatibility performances of the new heparin-coated Evodial dialyzers with/without systemic heparin reduction. After a 4-week wash-out period with reference polysulfone F70S dialyzers, 6 hemodialysis patients were sequentially dialyzed with Evodial, F70S, and Evodial dialyzers using 30% heparin reduction, each period of treatment was 4 weeks. Removal rates (RR) (urea, creatinine, and β2-microglobulin), dialysis dose, and instantaneous clearances (urea and creatinine) were measured as well as inflammatory (C-reactive protein, fibrinogen, interleukin 6, tumor necrosis factor α, and monocyte chemoattractant protein-1) and oxidative stress (OS) (superoxide anion, homocysteine, and isoprostanes) parameters at the end of each study period. Patients treated with Evodial or F70S dialyzers for 4 weeks presented comparable dialysis efficacy parameters including urea and creatinine RR, dialysis dose and instantaneous clearances. By contrast, a significantly lower but reasonably good β2-microglobulin RR was achieved with Evodial dialyzers. Regarding biocompatibility, no significant difference was observed with inflammation and OS except for postdialysis monocyte chemoattractant protein-1 which significantly decreased with Evodial dialyzers. Thirty percent heparinization reduction with Evodial dialyzers did not induce any change in inflammation but led to an improvement in OS as demonstrated by a decrease in postdialysis superoxide production and predialysis homocysteine and isoprostane. This bioactive dialyzer together with heparin dose reduction represents a good trade-off between efficacy and biocompatibility performance (improvement in OS with a weak decrease in efficacy) and its use is encouraging for hemodialysis patients not only in reducing OS but also in improving patient comorbid conditions due to lesser heparin side effects.     

Intradialytic complications during hemodialysis

With the advent of developments and advances in hemodialysis machine technology, dialysate water purification, and dialyzers, the clinical spectrum of intradialytic complications has changed over the decades. In the pioneering days of hemodialysis, patients could develop allergic reactions to dialyzer membranes, sterilizing and reprocessing agents, coupled with machines that could not accurately control ultrafiltration rates, and chemically and bacterially contaminated dialysate. Whereas today, although cardiovascular problems remain the most common intradialytic complication, these are mainly due to the time restraints of trying to cope with excessive dialytic weight gains and achieve target dry weight on a thrice weekly schedule, coupled with an aging elderly dialysis population with increasing co-morbidity.