On-line Urea Research Articles

Estimation du volume de distribution de l’urée chez le patient hémodialysé

Background On-line urea clearance estimation, currently available on some dialysis monitors, makes it possible to calculate the dialysis dose Kt and thus allows to estimate Kt/ V for each session, providing an estimation of urea distribution volume ( V) at equilibrium assumed equal to total body water. Methods Three methods suitable for routinely estimating V, using the anthropometric Watson formula ( V Wat), the body composition monitor (BCM) device (Fresenius Medical Care) based on bio-impedance analysis ( V imp) and the indirect estimation ( V Daug) obtained from measurement of Kt/ (Kt/ V) sp ratio respectively are compared during 25 dialysis sessions in 15 patients to a direct estimation ( V DDQ) obtained by direct quantification of dialysis (DDQ) considered as the gold standard in hemodialysis patient.. Results V Watson overestimates V DDQ by about 20%. The values of V imp (29.1 ± 5.6 L) and V Daug (29.5 ± 4.6 L) are in agreement with V DDQ (29.9 ± 5.2 L). Correlation coefficient with V DDQ is better for V imp ( r = 0.94) than for V Daug ( r = 0.85). Conclusion Bio-impedancemetry using BCM and indirect method using the second generation Daugirdas equation are two methods of clinical interest for estimating V. Bio-impedancemetry does not require blood sample, but it needs to have a specific device at disposal.

Different hemoglobin levels on the clearance rate of urea

Objective Online clearance monitoring explore different hemoglobin level of maintenance hemodialysis patients the effects of urea clearance rate.Methods 29 cases of patients will be randomized according to hemoglobin level divided into two groups,A group:Hb:100～130 g/L B group:Hb:50～99 g/L The use of online urea clearance rate monitor(OCM) observate the changes of area clearance rate(KT/V).Results A group:KT/V:1.22±0.8 Bgroup:KT/V:1.54 ±1.0 Between the two groups were significantly different(P＜0.05).Conclusion For maintenance hemodialysis patients,High levels of hemoglobin,the value of KT/V is lower;Low levels of hemoglobin,the value of KT/V is higher. Key words: Hemoglobin; Urea clearance rate; Online clearance monitoring

Dosing intermittent haemodialysis in the intensive care unit patient with acute renal failure--estimation of urea removal and evidence for the regional blood flow model

Blood-side dosing methods may overestimate urea removal in comparison to dialysate-side measurements during intermittent HD (IHD) for acute renal failure (ARF). The present study sought to quantify this mass balance error (MBE) and explore potential explanatory factors. Prospective, formal, blood-side urea kinetic modelling was performed in serial sessions (n = 42) in 18 intensive care unit ARF patients. Three blood-side estimates of urea removal were calculated and these were compared to urea removal derived from fractional dialysate sampling and use of an on-line urea monitor. We also examined urea rebound in these patients, as expressed by the intercompartmental urea clearance (Kc), and in a subset of patients examined the relation of Kc to cardiac output and systemic vascular resistance (SVR). The mean % MBE (MBE = blood - dialysate-estimated urea removal) was about 9% using conventional two-pool modelling based on a 60-min post-dialysis blood urea nitrogen (BUN) with or without the use of one or more intra-dialytic BUN values. The extent of MBE could not be explained by the clinical or dialytic variables that were measured. Part of the MBE error was due to overestimation of the intradialytic BUN profile, because model-independent profiling of intra-dialytic BUN values to compute urea removal reduced the MBE to approximately 6%. The log Kc was correlated with cardiac output and showed trends towards an inverse correlation with SVR. Classical, two-pool, blood-side UKM produces a modest overestimate of urea removal in IHD for critically ill ARF patients. The source of this small, residual MBE is unknown. The amount of urea rebound, as reflected by Kc, varied among patients and associated with cardiac output and SVR, as predicted by the regional blood flow model.

Haemodialysis with on-line monitoring equipment: tools or toys?

On-line monitoring of chemical/physical signals during haemodialysis (HD) and bio-feedback represents the first step towards a 'physiological' HD system incorporating adaptive and logic controls in order to achieve pre-set treatment targets. Discussions took place to achieve a consensus on key points relating to on-line monitoring and bio-feedback, focusing on the clinical applications. The relative blood volume (BV) reduction during HD can be monitored by optic devices detecting the variations in concentration of haemoglobin/haematocrit. BV changes result from an equilibrium between ultrafiltration and the refilling capacity. However, BV reduction has little power in predicting intra-HD hypotensive episodes, while the combination of the patient-dialysate sodium gradient, the relative BV reduction between the 20th and 40th minute of HD, the irregularity of the profile of BV reduction over time and the heart rate decrease from the start to the 20th minute of HD predict intra-HD hypotension with a sensitivity of 82%, a specificity of 73% and an accuracy of 80%. A bio-feedback system drives the relative BV reduction according to desired values by instantaneously changing the ultrafiltration rate and the dialysate conductivity. This system has proved to reduce the incidence of intra-HD hypotension episodes significantly. Ionic dialysance and the patient's plasma conductivity can be calculated easily from on-line inlet and outlet dialysate conductivity measurements at two different steps of dialysate conductivity. Ionic dialysance is equivalent to urea clearance corrected for recirculation and is a tool for continuously monitoring the dialysis efficiency and detecting early problems with the delivery of the prescribed dose of dialysis. Given the strict and linear relationship between conductivity and sodium content, the conductivity values replace the sodium concentration values and this permits the development of a conductivity kinetic model, by means of which sodium balance can be achieved at each dialysis session. The conductivity kinetic model has been demonstrated to improve intra-HD cardiovascular stability in hypotension-prone patients significantly. Ionic dialysance is also a useful tool to monitor vascular access function, as it can be used to obtain serial measurements of vascular access blood flow. On-line urea monitors provide detailed information on intra-HD urea kinetics and delivered dialysis dose, but they are not in widespread use because of the costs related to the disposable materials (e.g. urease cartridge). The body temperature monitor measures the blood temperature at the arterial and venous lines of the extra-corporeal circuit and, thanks to a bio-feedback system, is able to modulate the dialysate temperature in order to influence the patient's core body temperature, which can be kept at constant values. This is associated with improved intra-HD cardiovascular stability. The module can also be used to quantify total recirculation. On-line monitoring devices and bio-feedback systems have evolved from toys for research use to tools for routine clinical application, particularly in patients with clinical complications. Conductivity monitoring appears the most versatile tool, as it permits quantification of delivered dialysis dose, achievement of sodium balance and surveillance of vascular access function, potentially at each dialysis session and without extra cost.

Comparative Study between Classic and Newer Methods for the Evaluation of Hemodialysis Adequacy

Aim: The comparative study of hemodialysis (HD) adequacy of Kt/V measurement between classic method (Daugirdas formula) and urea sensor monitor (online).Patients and methods: 30 patients with end‐stage renal failure undergoing dialysis were studied. A comparative evaluation of HD adequacy during the same session was done with two different methods: (1) blood samples were drawn in the beginning and in the end of HD session for the measurement of blood urea nitrogen (BUN) and after measurement of HD adequacy by 3rd generation Daugirdas formula and (2) urea sensor monitor use for continuous HD adequacy measurement during HD session.Results: There was statistically significant correlation of Kt/V Daugirdas with Kt/V online (r = 0.8, p < 0.001). Also there was statistically significant correlation between solute removal index (SRI), Kt/V Daugirdas (r = 0.81, p < 0.001) and Kt/V online (r = 0.92, p < 0.001). From nutrition indices that were measured, the protein catabolic rate (PCR) had marginal negative correlation with the two compared adequacy indices, Kt/V Daugirdas (r = −0.24, p < 0.03), and Kt/V online (r = −0.17, p < 0.03) although the nPCR (normalized PCR) had marginal positive correlation (r = 0.35, p < 0.05) (r = 0.42, p < 0.05).Conclusions: The use of online urea sensor monitors contributes to the easy measurement of adequacy and nutrition indices and hence complicated mathematical formulas are not necessary. The results of these measurements are reliable and comparable with classic methods of HD adequacy evaluation.

Near-infrared spectroscopic measurement of urea in dialysate samples collected during hemodialysis treatments.

Single-beam spectra were collected over the combination region of the near-infrared spectrum for 80 samples collected from 15 people over a two-week period. Partial least-squares (PLS) regression was used to generate an optimized calibration model for urea. PLS calibration models accurately measure urea in the spent dialysate matrix. Prediction errors are on the order of 0.15 mM, which is sufficient for the clinical assessment of the dialysis process. In addition, the feasibility of a global calibration model is demonstrated by generating a calibration model from samples and spectra obtained from 12 people to predict the level of urea in samples collected from 3 different people. In this case, the standard error of prediction is 0.09 mM. Spectra were modified in order to systematically examine the impact of resolution and noise. Little impact is observed by altering the spectral resolution from 4 to 32 cm-1. Spectral noise, however, plays an important role in the accuracy of these calibration models. Increasing the magnitude of the spectral noise increases the prediction errors and increases the width of the spectral range necessary for extracting the analytical information. The utility of the method is demonstrated by analyzing dialysate samples collected during actual dialysis treatments. In addition, the necessary resolution and spectral quality necessary for reliable on-line urea monitoring is identified. These findings indicate that a dedicated, on-line urea spectrometer must posses a resolution of 16 cm-1 coupled with a sample thickness of 1.5 mm and spectral noise levels on the order of 25 micro-absorbance units when measured as the root-mean-square (RMS) noise of 100% lines.

Dialysate-side urea kinetics. Neural network predicts dialysis dose during dialysis.

Determination of the adequacy of dialysis is a routine but crucial procedure in patient evaluation. The total dialysis dose, expressed as Kt/V, has been widely recognised to be a major determinant of morbidity and mortality in haemodialysed patients. Many different factors influence the correct determination of Kt/V, such as urea sequestration in different body compartments, access and cardiopulmonary recirculation. These factors are responsible for urea rebound after the end of the haemodialysis session, causing poor Kt/V estimation. There are many techniques that try to overcome this problem. Some of them use analysis of blood-side urea samples, and, in recent years, on-line urea monitors have become available to calculate haemodialysis dose from dialysate-side urea kinetics. All these methods require waiting until the end of the session to calculate the Kt/V dose. In this work, a neural network (NN) method is presented for early prediction of the Kt/V dose. Two different portions of the dialysate urea concentration-time profile (provided by an on-line urea monitor) were analysed: the entire curve A and the first half B, using an NN to predict the Kt/V and compare this with that provided by the monitor. The NN was able to predict Kt/V is the middle of the 4h session (B data) without a significant increase in the percentage error (B data: 6.69% +/- 2.46%; A data: 5.58% +/- 8.77%, mean +/- SD) compared with the monitor Kt/V.

BLOOD PUMP SPEED, RECIRCULATION, AND UREA CLEARANCE IN HEMODIALYSIS PATIENTS WITH DYSFUNCTIONAL CATHETERS

Urea clearance varies with dialysis blood pump speed (Qb) for well-functioning hemodialysis (HD) catheters. Patients with dysfunctional HD catheters often have reduced Qb due to catheter thrombosis, fibrin sheath, or central venous stenosis. One method of achieving higher Qb is to reverse the position of the HD lines (i.e., connect the arterial line to the venous port and vice versa). However, line reversal is associated with greater catheter access recirculation (AR) and resultant decreased urea clearance. Objective: To determine the effect of line reversal with varying Qb on % AR, and urea clearance in HD patients with dysfunctional. Methods: 7 patients with dysfunctional internal jugular catheters in our HD unit were identified. During a regularly scheduled HD session, we measured each patient's on-line urea clearance using dialysance (Diascan) at the maximum achievable Qb with the lines in the normal position, and at varying Qb with the lines in reversed position. With lines in the reversed position at Qb of 200, 300 and 400 ml/min, dialysance was 123, 159, and 195 ml/min respectively (figure).Conclusions: Line reversal is associated with significant AR in patients with dysfunctional catheters. However, in patients with dysfunctional HD catheters in whom the maximum achievable Qb is ≤ 200 ml/min in the normal position, greater urea clearance can be achieved by line reversal and increasing Qb to ≥ 300 ml/min. Dialysance was used as a surrogate measurement of urea clearance. AR was also measured using ultrasound dilution technique. (Transonic machine) Linear regression was used to model the relationships between Qb, dialysance and AR. Results: AR in dysfunctional IJ catheters with lines in the normal position was 0% for all Qb in the range 150–400 ml/min. According to the regression model, AR with lines in the reverse position was 19% at Qb 300 ml/min. Maximum achievable dialysance with lines in the normal position for Qb ≤ 200 ml/min was 144 ml/min.

Blood Pump Speed, Recirculation, and Urea Clearance in Hemodialysis Patients with Dysfunctional Catheters

Urea clearance varies with dialysis blood pump speed (Qb) for well-functioning hemodialysis (HD) catheters. Patients with dysfunctional HD catheters often have reduced Qb due to catheter thrombosis, fibrin sheath, or central venous stenosis. One method of achieving higher Qb is to reverse the position of the HD lines (i.e., connect the arterial line to the venous port and vice versa). However, line reversal is associated with greater catheter access recirculation (AR) and resultant decreased urea clearance. Objective : To determine the effect of line reversal with varying Qb on % AR, and urea clearance in HD patients with dysfunctional. Methods : 7 patients with dysfunctional internal jugular catheters in our HD unit were identified. During a regularly scheduled HD session, we measured each patient's on-line urea clearance using dialysance (Diascan) at the maximum achievable Qb with the lines in the normal position, and at varying Qb with the lines in reversed position. With lines in the reversed position at Qb of 200, 300 and 400 ml/min, dialysance was 123, 159, and 195 ml/min respectively (figure).Conclusions: Line reversal is associated with significant AR in patients with dysfunctional catheters. However, in patients with dysfunctional HD catheters in whom the maximum achievable Qb is ≤ 200 ml/min in the normal position, greater urea clearance can be achieved by line reversal and increasing Qb to ≥ 300 ml/min. Dialysance was used as a surrogate measurement of urea clearance. AR was also measured using ultrasound dilution technique. (Transonic machine) Linear regression was used to model the relationships between Qb, dialysance and AR. Results: AR in dysfunctional IJ catheters with lines in the normal position was 0% for all Qb in the range 150–400 ml/min. According to the regression model, AR with lines in the reverse position was 19% at Qb 300 ml/min. Maximum achievable dialysance with lines in the normal position for Qb ≤ 200 ml/min was 144 ml/min.

Significance of distribution volume in dialysis quantification.

The urea distribution volume is in several ways an important parameter in the treatment of end-stage renal disease (ESRD) patients. It has a major impact on the relative dose of dialysis treatment as measured by Kt/V. It is also important in the assessment of fluid status, which has a direct influence on blood pressure. Nevertheless, urea distribution volume is usually not measured on a regular basis, probably because it has been perceived as a relatively complicated measurement. With the arrival of on-line monitors for dialysate urea this situation has improved radically. In this article a number of volume determination methods are discussed, including some new methods based on on-line dialysate urea monitoring, which are shown to perform well in comparison to reference methods.

Future directions in dialysis quantification.

The influence of dialysis prescription on outcome is well established, and currently the amount of dialysis prescribed is based on small molecular weight toxin removal as represented by the clearance of urea. The "normalized dose of dialysis" (Kt/V(urea)) concept is well established. Most techniques for dialysis quantification require that blood samples be taken at the beginning and after the completion of dialysis. The postdialysis sample, however, gives cause for concern because of the "rebound phenomenon" due to nonuniform distribution of urea among body compartments. Blood samples give "indirect" measures of dialysis quantification. Thus direct urea concentration measurements in dialysate may be superior in urea kinetic modeling and these may be made "real time" during dialysis. It is with real-time monitoring that future advances in dialysis quantification will take place. These will be of two types. The first will analyze blood water or dialysate samples for urea content multiple times throughout the treatment; the second will assess the on-line clearance of urea using surrogate molecules such as sodium chloride, the clearance being determined by conductivity measurements. On-line urea monitoring is based on the action of urease on urea in a water solution and measurement of the resultant ammonium ions, which are measured directly by a specific electrode or indirectly by conductivity changes. Differences in blood-side versus dialysate-side urea monitors exist which reflect the parameters they can provide, but with both, the standard urea kinetic measurements of Kt/V and nPCR (nPNA) are easily obtainable. A range of additional parameters can be derived from dialysate-side monitoring such as "whole-body Kt/V," "pretreatment urea mass" and "whole-body urea clearance," which are worthy of future studies to determine their roles in adequacy assessment. Conductivity clearance measurements are made by examining the conductivity differences between dialysate inlet and outlet measured at two different dialysate inlet concentrations. This allows for the calculation of the electrolyte (ionic) dialysance, which is equal to the "effective" urea clearance, that is, the clearance that takes into account recirculation effects that reduce hemodialysis efficiency. The continuous reading of effective ionic clearance will allow an average value for K to be obtained for that dialysis, and hence the parameter K x t as an indication of dialysis dose is easily and accurately obtained for every treatment. The conductivity technology is cheap and rugged, and thus expanded use can be expected. Urea monitors have an inherent cost and require maintenance, and perhaps will remain researchers' tools for the present. The methodologies can complement each other; the addition of an accurate and independent value for K to dialysate based urea monitoring is like having simultaneous blood- and dialysate-side monitoring, and allows further increase in measurable parameters.

Adequacy in hemodialysis: New concepts derived from online urea monitoring

The estimation of urea kinetic parameters [urea generation rate (Gu), normalized protein catabolic rate (NPCR), and dialysis dose (Kt/V)] is routinely performed during a single hemodialysis session as a representative sample of a stable series. To ascertain whether the stability assumption is tenable and to estimate the variability of urea kinetic parameters, a number of stable patients on regular dialysis treatment in their usual clinical setting were followed. Thirteen stable patients on regular hemodialysis aged 61 +/- 11 were monitored from 5 to 24 weeks (median, 10 weeks) with the urea biosensor system in double-chamber hemodiafiltration. Body weight did not change appreciably. Residual renal function was negligible or absent. Weekly averaged urea concentration (TACw), Gu, NPCR, and Kt/Veq were calculated, and their serial patterns and interrelationships were evaluated through graphical analysis and linear regression. In six patients, the urea pool was substantially unchanged, but variability of Gu and Kt/V was comparable to that of the other groups. In three patients, body urea pool increased. Gu went from 4. 78 +/- 0.44 to 5.40 +/- 0.65 mg/min, and Kt/V went from 1.25 +/- 0. 25 to 1.34 +/- 0.31. In four patients, body urea pool decreased; Gu went from to 6.55 +/- 1.91 to 5.85 +/- 2.26 mg/min, and Kt/V did not change appreciably. Parameters might change in a nearly linear trend or occasionally as abrupt or oscillating phases. Gu was the main factor involved, and the only one affecting four of the seven unstable patients. Kt/V was never solely involved. Our data indicate that the estimation of urea kinetic parameters is often affected by a non-negligible degree of variability, which can be ascribed to the variability of the dialytic dose delivered and, above all, to the daily changes of diet protein assumption.

Urea as a marker of adequacy in hemodialysis: Lesson from in vivo urea dynamics monitoring

"Dialysis dose," a concept developed by Sargent and Gotch based on urea kinetic modeling, is a useful and recognized tool that is used to quantitate and optimize a dialysis-efficacy program. However, it has been shown that oversimplification of the "dialysis adequacy" concept to the Kt/V index might lead to dramatic underdialysis and subsequent deleterious consequences on morbidity and mortality of dialysis patients. With this perspective, the determination of Kt/V must be very cautious and rely on accurate measurement of postdialysis urea concentration and its use integrated as a tool in a quality-assurance process. In this study, we analyzed urea dynamics by means of a blood side (ultrafiltrate) continuous online urea monitoring system interfaced with a two-pool model hosted in a microcomputer. The study was designed to provide instantaneous dialysis performances (body and dialyzer clearances, dialyzer mass transfer coefficient) and to determine the in vivo functional permeability characteristics of the patient [intercompartment urea mass transfer coefficient (Kc)]. Thirteen end-stage renal disease patients (age 54 +/- 16 years; 12 male and 1 female) were studied during nine consecutive dialysis sessions (3 weeks). Urea kinetics obtained from the urea monitoring system fitted closely the urea kinetic modeling prediction, confirming the validity of the double-pool model structure. Effective in vivo urea mass transfer coefficient averaged 912 +/- 235 mL/min/1.73 m2, a value close to those reported with more invasive methods. Large variations ranging from 363 to 1249 mL/min were observed among patients, confirming very large interindividual patient permeability differences. Interestingly, the urea mass transfer coefficient was inversely correlated with the postdialysis rebound values. Intraindividual variations were also noted as a function of time denoting functional changes in urea mass transfer coefficient values. The urea distribution volume was 38.1 +/- 7, 8 L (53 +/- 8% body weight). V1 referring to the extracellular volume and V2 to the intracellular volume were 9 +/- 2 L (13 +/- 2% body weight) and 29.2 +/- 6.6 L (41 +/- 1.3% body wt), respectively. The extracellular/intracellular volume ratio was 0.31 (approximately one third) and was not as usually defined by the paradigm 1/2 ratio. Online double-pool urea kinetic modeling gave a new insight in urea kinetic modeling approach. Urea dynamics fit perfectly a double-compartment model structure. Accessible extracellular volume to hemodialysis is smaller than expected. The in vivo urea mass transfer coefficient must be considered as an individual and variable characteristic of ESRD patients that should be taken into consideration when prescribing the hemodialysis schedule.

The final word

The content of this Supplement issue reflects our personal experiences during 40 years of dialysis treatment in a remarkable way. We have witnessed tremendous progress in the treatment of end-stage renal disease (ESRD). However, uremia remains a constellation of signs and symptoms that, in large part, await definitive elucidation. There is growing awareness that it is the entire spectrum of accumulated products that play a pathophysiological role, rather than an as yet unknown "uremic toxin." It is not surprising that the question of what actually constitutes adequate dialysis for ESRD patients is still a controversial and debated issue within the dialysis community. The term "adequate" may, in fact, refer not only to the "dose," but also to the "systems' biocompatibility," the reduction of cardiovascular and atherosclerotic risk factors, and the minimization of chronic inflammation. The previously mentioned attributes of dialysis adequacy have developed during the last decade as fast-evolving areas of pathophysiological research in dialysis, and this issue contains contributions from different individuals who have actively participated in their development. We, as Guest Editors, avoided giving practical guidelines, but felt we should highlight whatever consensus could be found in the dialysis community. When this was not possible, we felt that both sides of the ongoing controversies should be presented, with the aim of leaving the reader to make a final conclusion. We were motivated by the fact that at the turn of the new millennium, we all are facing a new era of clinical medicine that whenever new, more sophisticated investigations become available, less and less space will remain for simplistic empiricism. The clinical practice of hemodialysis is no exception to this trend. The still unacceptably high mortality/morbidity rates in ESRD patients and the high cost of ESRD management are imperatives for the dialysis community to direct all efforts toward a more comprehensive understanding of the underlying mechanisms and for possible corrective measures.

Evaluation of Pre- and Postdilutional On-Line Hemodiafiltration Adequacy by Partial Dialysate Quantification and On-Line Urea Monitor

On-line highflux hemodiafiltration (HDF) is a clinically interesting and effective mode of renal replacement therapy, which offers the possibility to obtain an increased removal of both small and large solutes. The fundamental role of urea kinetic monitoring to assess dialysis adequacy in conventional hemodialysis has been widely studied. Both direct measurement of the urea removed by the modified direct dialysate quantitation (mDDQ) based on partial dialysate collection (PDC) and dialysate-based urea kinetic modeling (DUKM) using urea monitor have been advocated. The validity of this assessment tool in the patients with on-line HDF remained unclear. The aims of this investigation were (1) to compare the delivered Kt/V, urea mass removal (UMR), solute removal index (SRI) and normalized protein catabolic rate (nPCR) between pre- and postdilutional high-flux HDF; (2) to verify and compare the efficiency of pre- and postdilutional HDF using DUKM with on-line dialysate urea sensor, and mDDQ with partial dialysate collection. During both mode of HDF, the paired analysis urea removed and Kt/V showed no significant difference. Using mDDQ, mean values for predilutional mode were as follows: Kt/V 1.53 ± 0.01 UMR, 16.8 ± 0.3 g/session; urea clearance 178 ± 18 ml/min; SRI 75.5 ± 7.7%; urea distribution volume (V) 28.3 ± 1.2 liters; nPCR 1.34 ± 0.18 g/kg/day; on the other hand, mean values for postdilutional mode were Kt/V 1.58 ± 0.01; UMR 17.10 ± 0.28 g/session; urea clearance 184 ± 21 ml/min; SRI 77.2 ± 3.5%; urea distribution volume, 27.8 ± 1.5 liters; nPCR 1.34 ± 0.19 g/kg/day. The mean value of urea generation rate was 5.82 ± 1.12 mg/min during HDF. Our results showed that dialysis adequacy was achieved with both high-volume predilutional HDF and postdilutional HDF. These two modes of HDF provided similar and adequate small solute clearance. In addition, we found that on-line analysis of urea kinetics is a reliable tool for quantifying and assuring delivery of adequate dialysis.

Assessment of efficiency using on-line urea kinetic modeling in hemodiafiltration.

Urea kinetics has recently been re-evaluated using an on-line urea monitoring system applied to hemodiafiltration. This system allows evaluation of different components possibly responsible for the gap between prescribed and delivered dose of dialysis, such as access and cardiopulmonary recirculation, and altered dialysis parameters, such as blood flow and dialysate flow rates. Furthermore, the system allows prediction of postdialysis rebound urea concentrations. The aim of the present study was to apply the on-line urea monitoring system to assess the dialytic efficiency of double chamber hemodiafiltration in different conditions of blood-dialysate flow rates, reinfusion volumes, and dialyzer configurations (high + low flux membranes or high + high flux membranes) in 10 patients (age, 60 +/- 9 years; dry weight, 65 +/- 5 kg). There was a significantly lower Kt/V (K, dialyzer clearance; t, dialysis time; V, urea distribution volume) at equilibrium with the high + high vs high + low flux configuration, possibly because of a higher tendency toward urea compartmentalization. This difference was evident when reinfusion was performed post dilution. These studies support the concept that small molecular weight uremic toxins may be more efficiently removed using low flux membranes in a modified form of hemodiafiltration.

The other side of the coin: interdialytic weight gain as an index of good nutrition.

Excessive interdialytic weight gain (IDWG) is usually attributed to fluid and sodium overload. Abnormal thirst regulation, hormonal derangements, and social, cultural, and psychological habits may account for low compliance with fluid and salt restrictions. However, food intake is an important determinant of IDWG, and high IDWG may reflect the nutritional status of hemodialyzed patients, rather than their scanty compliance. The relationship between IDWG, efficacy of dialysis, and nutritional status was investigated in 38 patients (28 men and 10 women), in whom urea kinetics was studied by means of an on-line urea sensor (UM 1000, Baxter Healthcare, McGraw Park, IL), and Kt/V and protein catabolic rate (PCR) were calculated. Records from 161 dialysis sessions were analyzed and grouped according to their IDWG (group A, weight gain > 5% and group B, weight gain < 5% of dry body weight). In group A, Kt/V, solute removal index, urea reduction ratio, predialytic blood urea nitrogen (BUN), urea removed, and PCR were statistically higher than in group B (P < 0.05). Regression analysis showed a significant and positive correlation between IDWG and PCR. In 17 of 38 patients with steadily high IDWG, serum albumin levels, predialytic BUN, and PCR were significantly higher than in patients with low IDWG (P < 0.05). Sex and predialytic blood pressure did not correlate with IDWG; in contrast, age negatively affected both IDWG and PCR (age v IDWG and age v PCR, r = 0.22; P < 0.008 and P < 0.006, respectively). These results confirm that high IDWG is associated with better nutritional status.

A New Biosensor for Continuous Monitoring of the Spent Dialysate Urea Level in Standard Hemodialysis

This study gives the results in terms of precision and repeatability of a new on-line urea monitoring system (Ureascan P2 Hospal) capable of measuring the urea concentrations in the spent dialysate. The Ureascan P2 Hospal (UP2H), fitted on single-pass dialysis machines (Integra-Hospal), functions by the presence of a disposable mini-reactor containing urease. The passage through the reactor of a minimum quantity of spent dialysate from the filter diluted with a pH 7 buffer solution (1 ml/min) increases its ionic strength, which is detected by a differential measurement of conductivity in proportion to the urea concentration in the dialysis liquid. We studied 13 dialysis sessions, with bicarbonate buffer, in 8 anuric patients. From 4 to 7 dialysate samples were taken during each treatment to determine the urea and 65 samples were analysed overall. Urea values from the UP2H were compared with those measured on the Dimension Du Pont analyser. Simple linear regression analysis showed an excellent correlation between the 2 measuring methods (r=0.987; p<0.001). The Bland-Altman test gave an average difference between the urea values measured with the UP2H and in the laboratory of 1.3+/-1.2 mg/dl. The agreement limits between 2 SD were -1.2 mg/dl and +3.8 mg/dl respectively. In conclusion, the UP2H we have developed has proved to be a reliable and very useful instrument for adapting, through the urea kinetic mathematical models, the dialysis dose for individual patients.

Evaluation of high-flux hemodiafiltration efficiency using an on-line urea monitor

On-line urea monitoring of the effluent dialysate offers a real-time assessment of dialysis efficiency and metabolic/nutritional characteristics of hemodialysis patients. Quantitative parameters were evaluated by dialysate urea kinetic modeling (DUKM) with an on-line urea sensor in 23 patients treated by high-flux hemodiafiltration (HDF) (215 sessions of 210 to 240 minutes with a mean blood flow rate of 367 +/- 44 mL/min). Overall, the mean effective Kt/V was 1.52 +/- 0.29, the urea mass removed (22.8 +/- 5.5 g/session or 814 +/- 198 mmol/session), the solute removal index (SRI) 73% +/- 6.1%, and the mean normalized protein catabolic rate (nPCR), 1.15 +/- 0.31 g/kg/day. Blood urea kinetic modeling (BUKM), based on pre- and postsession urea concentrations, using equations from Daugirdas and Garred to calculate equilibrated Kt/V and nPCR, respectively, were in good agreement with DUKM, the differences observed appearing not clinically relevant. The variability of evaluated parameters was verified over consecutive sessions for a mean period of 3 weeks in the entire group. Mean variation in Kt/V was 8%; in urea mass removal, 18%; and in nPCR, 18%. When assessed over 1 week in a subgroup of 13 patients, Kt/V and PCR remained relatively stable, and urea mass removal per- and postsession declined from 23.5 +/- 8.0 g (840 +/- 285 mmol) to 18.7 +/- 6.3 g (667 +/- 225 mmol) from the first to the third session of the week, most likely as a consequence of interdialytic intervals. Predialysis urea concentrations followed the same trend. In the current study, DUKM with on-line urea sensor has confirmed that HDF is a highly efficient renal replacement modality; the variability observed in quantitative parameters supports a need for frequent adequacy monitoring. On-line urea monitoring of effluent dialysate is a simple device that provides the opportunity to tailor treatment to patient needs. (Am J Kidney Dis 1998 Jan;31(1):74-80)

A simple and accurate method to determine equilibrated post-dialysis urea concentration

Fractional urea clearance or KtIV is usually determined from a two-point method using preand post-dialysis blood urea concentrations [1, 2]. Kt/V then becomes critically dependent upon post-dialysis urea concentration [3]. Since immediate post-dialysis urea sampling does not account for recirculation and rebound, it tends to overestimate hemodialysis efficiency [4]. This may occur especially with short, highly efficient modalities [5—8]. A delayed post-dialysis urea determination allows a more accurate estimation of the effective dialysis dose. Thus, special attention must be paid to sample timing for post-dialysis urea concentration. Shortly-delayed blood sampling (2 mm after the end of the session) should correct for vascular access and cardiopulmonary recirculation [9]. However, the internal resistance to urea transfer from different compartments, which explains a large part of the observed urea rebound, is further delayed [10, 11]. Consequently, late blood sampling (30 to 45 mm after the end of the session) has been recommended to obtain an equilibrated urea concentration, but such a delay is inconvenient in routine clinical practice. To overcome this problem, Smye et al have suggested a third early intradialytic blood sample for urea (70 to 90 mm from the beginning) that may be used to calculate equilibrated post-dialysis urea concentration [12]. Indeed, the Smye model has proven accurate in the prediction of equilibrated urea [13, 14]. However, the requirements of this approach (a third blood sample and mathematical calculation) may limit its clinical application. In a previous study concerning the determination of urea rebound using an on-line urea sensor on the ultrafiltrate outflow, the following observations were made: (1) rebound amplitude increased with session efficiency; (2) urea concentration reached a plateau 30 minutes post-session; (3) intradialytic urea concentration 30 minutes before the end of the session was equivalent to the post-dialysis equilibrated value. The present study was undertaken to validate this last observation [15].