Does hemodiafiltration improve the removal of homocysteine?

High prevalence of hyperhomocysteinemia is common in hemodialysis (HD) patients and could contribute to worsen the cardiovascular risk. Beyond vitamin B status, dialysis modality itself could influence homocysteine (Hcy) levels. The objective was compare the reduction rate (RR) of Hcy and cysteine in stable dialyzed patients treated by standard HD or hemodiafiltration (HDF). Seventy‐five patients undergoing stable dialysis through standard high‐flux HD (n = 35) or HDF (n = 40) were included. Biological parameters were determined before and after a midweek dialysis session. Urea percent reduction per session and Kt/V index (K, body urea clearance, T, time of dialysis, and V, urea distribution volume), defined as a marker of dialysis efficacy, were similar between HD and HDF groups. By contrast, higher RR of beta2 microglobulin (β2m) was observed in HDF compared with HD (78.6 vs. 72.0%, respectively; P < 0.001). Likewise, higher RR of Hcy was obtained with HDF compared to HD (46.0 vs. 41.5%, respectively; P < 0.05), whereas the RR of cysteine was similar in both groups. Interestingly, a positive correlation between Hcy RR and urea Kt/V index was observed (r = 0.29, P < 0.05) and between Hcy RR and β2m RR (r = 0.45, P < 0.001). Time‐averaged concentration (TAC) of Hcy was lower with HDF compared with HD (17.8 vs. 19.1 μmol/L, respectively), although not significant. There was no difference in median Hcy according to dialysis modality for neither pre‐ nor postdialysis levels. Significant higher removal of Hcy was observed with HDF compared with standard HD, although urea Kt/V index was similar. Enhanced removal of middle molecules, such as β2m, could be involved in Hcy RR improvement with HDF.     

Blood Urea Nitrogen Stability: A Feasibility Study for Home Hemodialysis Adequacy Testing Through Mail

Urea kinetic modeling measures the delivered dose of hemodialysis and is used to monitor dialysis adequacy. Obtaining samples for adequacy calculations is a challenge for home hemodialysis (HHD) patients. Ideally, the urea reduction ratio (URR) should be measured at a typical dialysis session; therefore, for HHD patients test specimens should be drawn at home and transferred to a clinical laboratory. Would blood urea nitrogen (BUN) remain stable if samples were mailed to the laboratory? To answer this question, BUN was measured in pre- and postdialysis samples from 20 patients over 8 days of laboratory storage. While BUN values varied among the patient population, neither pre- nor postdialysis values showed any significant variation during the 8-day storage time. These results suggest that BUN values are sufficiently stable for specimens to be drawn at home and mailed to a testing laboratory.     

Pilot study to assess increased dialysis efficiency in patients with limited blood flow rates due to vascular access problems

In the last few years, the number of hemodialysis patients with inadequate blood flow (Qb) rates has increased due to vascular access problems. To avoid a clinical status of underdialysis, these patients need long-lasting dialysis sessions. However, other factors aimed to optimize the dialysis dose have to be considered. High-efficiency convective therapies, such as online hemodiafiltration (HDF), are claimed to be superior to high-flux hemodialysis (HF-HD) in improving the dialysis efficacy, but treatment efficacy is strongly related to blood flow rate and infusion volumes. Online mid-dilution (HDF-MD) with the Nephros OL-pure MD190 represents a new HDF concept to increase the removal of middle molecules. In a cross-over clinical trial, 8 patients, with Qb eff <300 mL/min, received either online HDF-MD or HF-HD; Qd was 700 mL/min, the time duration was 240 min, and the filtration volume in HDF-MD was 112+/-7 mL/min. No differences were found for Kt/V, urea, and creatinine clearances. Clearance of both small phosphate (P) large beta(2)-microglobulin (beta(2)m), and leptin (L) solutes was significantly greater for MD (P 217+/-32, beta(2)m 85.5+/-10, L 42.6+/-18 mL/min) than for HF-HD (P 178+/-32, beta(2)m 71.9+/-13, L 32.1+/-12 mL/min). The results of this study indicate that HDF remains the best means of providing increased removal of large-molecular weight solutes even in patients with vascular access problems.     

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.     

Evaluation of polyethersulfone highflux hemodialysis membrane in vitro and in vivo

A new hemodialysis membrane manufactured by a blend of polyethersulfone (PES) and polyvinylpyrrolidone (PVP) was evaluated in vitro and in vivo. Goat was selected as the experimental animal. The clearance and the reduction ratio after the hemodialysis of small molecules (urea, creatinine, phosphate) for the PES membrane were higher in vitro than that in vivo. The reduction ratio of β₂-microglobulin was about 50% after the treatment for 4 h. The biocompatibility profiles of the membranes indicated slight neutropenia and platelet adhesion at the initial stage of the hemodialysis. Electrolyte, blood gas, and blood biochemistry were also analyzed before and after the treatment. The results indicated that PES hollow fiber membrane had a potential widely use for hemodialysis.     

Effect of Low Dialysate Flow Rate on Hemodialyzer Mass Transfer Area Coefficients for Urea and Creatinine

Recent work has shown that the dialyzer mass transfer area coefficient (K_oA) for urea increases when the dialysate flow rate is increased from 500 to 800 mL/min. In this study we determined urea and creatinine clearances for two commercial dialyzers containing polysulfone hollow fibers in vitro at 37°C, a nominal blood flow rate of 300 mL/ min, and dialysate flow rates (Q_d) ranging from 100 to 800 mL/min. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from solute concentrations in the input and output flows on both the blood and dialysate sides. Urea and creatinine K_oA values, calculated from the mean of the blood and dialysate side clearances, increased (p < 0.01) with increasing Q_d over the entire range studied. The increase in both urea and creatinine K_oA with increasing Q_d was proportional to the K_oA value. These data show that changes in Q_d alter small solute clearances greater than predicted assuming a constant K_oA.     

What is a surrogate marker for optimal dialysis?

To find a surrogate marker to obtain optimal dialysis delivery from the viewpoint of nutrition, 180 maintenance hemodialysis patients (109 males/71 females) were enrolled between October 1999 and June 2006 at our kidney center. In the 449 hemodialysis treatments, ultrapure dialysis solutions and high-flux synthetic membranes were utilized. Parameters were measured by Kt/V(urea) and postdialysis urea rebound, Kc (the cellular membrane clearance for urea), urea clear space (CS), %creatinine generation rate, %lean body mass, total body water, and so on. We examined the correlation between dialysis delivery and nutritional parameters: Kt/V(urea) and postdialysis urea rebound were found to be strongly and negatively correlated with nutritional parameters. However, Kc and CS have shown positive and strong correlations with nutritional parameters such as %creatinine generation rate, %lean body mass, and total body water as well. In addition, the age factor was correlated with Kt/V(urea) positively, and it influenced Kc and CS negatively. As a conventional dialysis parameter, Kt/V(urea) did not reflect nutrition, but Kc was found to improve nutrition due to the increase of the dialysis delivery. Therefore, Kc might be a reliable surrogate marker for optimal dialysis.     

Calculation of the clearance requirements for the development of a hemodialysis‐based wearable artificial kidney

Wearable artificial kidney (WAK) has been considered an alternative to standard hemodialysis (HD) for many years. Although various novel WAK systems have been recently developed for use in clinical applications, the target performance or standard dose of dialysis has not yet been determined. To calculate the appropriate clearance for a HD‐based WAK system for the treatment of patients with end‐stage renal disease with various dialysis conditions, a classic variable–volume two‐compartment kinetic model was used to simulate an anuric patient with variable target time‐averaged creatinine concentration (TAC), daily water intake volume, daily dialysis pause time, and patient body weight. A 70‐kg anuric patient with a HD‐based WAK system operating for 24 h required dialysis clearances of creatinine of at least 100, 50, and 25 mL/min to achieve TACs of 1.0, 2.0, and 4.0 mg/dL, respectively. The daily water intake volume did not affect the clearance required for dialysis under various conditions. As the pause time per day for the dialysis increased, higher dialysis clearances were required to maintain the target TAC. The present study provided theoretical dialysis doses for an HD‐based WAK system to achieve various target TACs through relevant mathematical kinetic modeling. The theoretical results may contribute to the determination of the technical specifications required for the development of a WAK system.     

Inadvertent postdialysis anticoagulation due to heparin line locks

Large-bore dual lumen in-dwelling venous catheters are used in hemodialysis. These catheters are usually locked with heparin after the treatment. This study addressed the underappreciated postdialysis coagulopathy that can result. Thirty-six patients were included: 7 dialyzed through arterio-venous fistulae, 29 through in-dwelling venous catheters. The latter group was further subdivided according to whether they received heparin or heparin-free dialysis. To assess the heparin lock, a full-dose heparin lock as well as a much weaker heparin lock and a citrate lock were used. To assess the coagulopathy, blood was taken 1 hr after dialysis. The activated partial thromboplastin time (APTT) and anti-Xa level was measured. Additionally, 6 venous catheters were removed and the amount of fluid expelled upon locking with saline was measured. Clotting from the patient group with arterio-venous fistulae was normal following dialysis. The patients with in-dwelling venous catheters and heparin locks had significantly deranged clotting; 6 out of 10 patients had abnormal APTT results. All patients with catheters, heparin-free dialysis, and heparin locks had deranged clotting (7 out of 7). The rate decreased significantly when heparinized saline was used as a lock. A subset of patients had a citrate lock rather than a heparin lock; the clotting results normalized in all but one patient. An in vitro study demonstrated immediate leakage of fluid from the end of the ports upon locking. Significant postdialysis anticoagulation can occur after dialysis, which can be attributed to the heparin line locks. This risk is considerably reduced when a citrate lock is used instead.     

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.     

Studies of phosphate dynamics during hemodialysis

Regulation of phosphate (PO₄) in hemodialysis patients is very difficult and ideal levels are rarely maintained. A high removal and a normal phosphate level is important, as high and low levels are both associated with morbidity and a very high mortality.
We studied phosphate dynamics and its relation to other small "uremic" molecules in 48 patients by measuring pre‐ and postdialysis levels and all removed phosphate, urea and creatinine (creat) in all dialysate during 455 dialyses done at different frequencies (freq): 3.7 ± 1.2, range 3–6 treatments per week and durations of dialysis (t): mean: 196 ± 95, range 80–560 min and with high (HF) and low flux membranes.
Kt/V‐PO₄, Kt/V‐urea and Kt/V‐creat, volumes (Vr) for all solutes and their relationships to frequency and duration of dialysis, urea clearance and predialysis phosphate were calculated.  

     

Use of Systemic Blood Urea Nitrogen Levels Obtained 30 Minutes before the End of Hemodialysis to Portray Equilibrated,Postdialysis Blood Urea Nitrogen Values

Blood urea nitrogen (BUN) levels obtained at 30 minutes before the end of dialysis were found to be closely similar to equilibrated, postdialysis BUN values obtained 30 minutes after the end of dialysis. Because of this similarity, the former BUN values can be used to derive equilibrated urea reduction ratio, or equilibrated Kt/V instead.     

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.     

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.     

Low dose heparin lock (1000 U/mL) maintains tunnelled hemodialysis catheter patency when compared with high dose heparin (5000 U/mL): A randomised controlled trial

Introduction Heparin is commonly used after hemodialysis treatments as a locking solution to prevent catheter thrombosis. The comparative efficacy and safety of different heparin concentrations to maintain catheter patency has been previously reported in retrospective studies. We conducted a prospective, randomised, controlled study of 1000 U/mL heparin (low dose) versus 5000 U/mL heparin (high dose) locking solution to maintain patency of tunnelled catheters. Methods One hundred patients receiving chronic, unit‐based hemodialysis with newly placed tunnelled hemodialysis catheters (less than 1 week) were randomly assigned to either a low dose (n = 48) or high dose heparin (n=52). The primary intention‐to‐treat analysis examined time to malfunction in both groups over a 90 day period. A secondary analysis compared baseline patient characteristics in relation to catheter malfunction. Findings Overall rate of catheter patency loss was 32% of catheters by 90 days. There was no significant difference in time to malfunction of catheters locked with low dose or high dose heparin (P = 0.5770). Time to catheter malfunction was not associated with diabetic, hypertensive or smoking status. There was no difference in mean delivered blood flow rate, venous and arterial pressure, and dialysis adequacy between low dose and high dose groups. No patient suffered a hemorrhagic complication requiring hospitalisation during the study period. Discussion Low dose heparin is adequate to maintain tunnelled hemodialysis catheter patency when compared with high dose heparin. The study also suggests that there is no relationship between catheter malfunction and diabetic, hypertensive or smoking status.     

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.     

Enhanced solute removal with intermittent, in-center, 8-hour nocturnal hemodialysis

Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end‐stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and β‐2‐microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice‐weekly, in‐center, 8‐hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45±7 years). Serum creatinine levels decreased from 9.2±1.9 to 3.0±1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7±1.9 to 2.5±0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8±5.5 mg/L predialysis to 14.9±7.0 mg/L at 8 hours (P<0.01). Dialysate‐side clearances of phosphorus and creatinine were 136±13 and 143±27 cm³/min, respectively. Phosphorus clearances were steadily maintained during the 8‐hour session. A total of 904±292 mg of phosphorus was removed during the 8‐hour treatment, with 501±174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one‐half of the session. The overall calculated B2M clearance was 55.1±40.3 cm³/min using the immediate post‐B2M value and 28.4±34.2 mg/L using the 30‐minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8‐hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.