Assessing the utility of the stop dialysate flow method in patients receiving haemodiafiltration
J. P. Traynor1,
H. A. Oun2,
P. McKenzie3,
I. R. Shilliday2,
I. G. McKay3,
A. Dunlop3,
C. C. Geddes1 and
R. A. Mactier4
1 Renal Unit, Western Infirmary, Glasgow, 2 Renal Unit, Monklands Hospital, Airdrie, 3 Renal Unit, Crosshouse Hospital, Kilmarnock, UK and 4 Renal Unit, Glasgow Royal Infirmary, Glasgow, UK
Correspondence and offprint requests to: J. P. Traynor, Renal Unit, Western Infirmary, Glasgow, UK. Email: jamie.traynor{at}northglasgow.scot.nhs.uk or jamie.traynor1{at}ntlworld.com
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Abstract
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Background. The stop dialysate flow (SDF) method of post-dialysis urea sampling is the most commonly used method in the UK. It can also be used with a published formula to predict 30 min equilibrated urea accurately. The method has not been validated in patients undergoing haemodiafiltration (HDF). Given the increased use of HDF across Europe, we felt it prudent to assess the utility of the SDF method and prediction equation in this modality.
Methods. Fourteen patients from two renal units were studied. Blood samples were taken at 1 min intervals from the arterial side of the dialysis circuit in the first 5 min after HDF had ceased whilst blood circulation continued. A peripheral sample was taken from the contralateral arm immediately after HDF had ceased and a 30 min sample was taken from the arterial needle. These samples were used to assess the utility of 5 min arterial blood urea and the 30 min prediction formula, respectively.
Results. Blood urea measured from the arterial circuit at 5 min correlated closely with the contralateral sample taken immediately post-HDF, with no significant difference (6.45±2.11 vs 6.52±2.19 mmol/l, P = 0.39). The use of 5 min arterial blood urea and prediction formula allowed an accurate prediction of 30 min urea (R2 = 0.96).
Conclusions. The use of the SDF method with a 5 min post-HDF arterial sample is valid in patients receiving HDF. The previously published prediction formula for estimating 30 min urea is also valid using the 5 min post-HDF sample.
Keywords: haemodiafiltration; Kt/V; post-dialysis urea rebound; stop dialysate flow; urea reduction ratio
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Introduction
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The stop dialysate flow method (SDF) [1] of post-dialysis urea sampling is now one of the three methods recommended by the UK Renal Association. It continues to be the method used by all renal units in Scotland and is the most commonly used method in the UK [2,3]. The use of the SDF method has been extended by the creation of a prediction equation that takes the 5 min sample and predicts urea at 30 min [4]. This can then be used to predict equilibrated Kt/V using the single pool model formula created by Daugirdas et al. with a reasonable degree of accuracy (R2 = 96%) [5].
The SDF flow method and the prediction equation were validated using data from patients receiving standard haemodialysis (HD) and have not been validated in patients receiving haemodiafiltration (HDF). This modality of dialysis is becoming more popular. Therefore, the importance of validating the SDF method with this modality is clear.
The SDF method makes use of a window in the post-dialysis urea rebound where access and cardio-pulmonary re-circulation are no longer taking place. In standard HD, this window exists between 4 and 6 min post-dialysis. The increased efficiency and range of molecules removed by HDF may cause a larger concentration gradient between the circulation and those tissues that are less well perfused. This in turn could lead to a higher rate of tissue rebound post-dialysis. Alternatively, the possible improvement in haemodynamic stability with HDF may lead to better perfusion of the peripheral tissues. This could then lead to a lower concentration gradient between tissue compartments and a lower rate of post-dialysis urea rebound.
Against this background of uncertainty, it was felt that the utility of the SDF method and 30 min prediction equation should be tested in patients receiving HDF.
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Subjects and methods
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Post-dialysis blood samples were taken from 14 patients receiving HDF for end-stage renal disease. Patients were recruited from two local hospitals that perform HDF (Monklands Hospital and Crosshouse Hospital). In both renal units, the majority of patients receive standard HD, and HDF is used in patients who have low measured urea clearance or, less commonly, have haemodynamic instability on standard HD. Both units perform on-line post-dilutional HDF.
A single sample was taken from the dry dialysis needle before dialysis started. Immediately at the end of dialysis, the machine was put into bypass, i.e. the haemodialysate infusion and filtrate removal were stopped whilst the blood pump speed remained unchanged. An immediate peripheral sample from the contralateral arm was taken (time 0 s). At the same time, 2 ml samples were taken from the arterial port of the extra-corporeal circuit. Further samples were taken from the arterial port at 60, 120, 180, 240, 300 and 360 s. Three investigators conducted the serial blood sampling to ensure exact timing. The patients were then taken off HDF with the arterial needle left in situ, having been flushed with 0.9% saline. At 30 min post-dialysis, 20 ml of blood was aspirated from the arterial needle before the final 2 ml sample was taken for analysis. It was anticipated that these earlier samples would provide a picture of post-dialysis rebound and identify the best window for sampling, whereas the 30 min sample would allow for most of the dialysis rebound [6,7] and provide a gold standard by which to assess the formula for predicting 30 min equilibrated urea.
Identifying the window period for haemodiafiltration
Urea concentration in the arterial port samples (A0, A60, A120, A180, A240, A300 and A360) was compared with urea concentration in the sample in the contralateral arm at 0 s (t0) to identify the window period when access and cardio-pulmonary re-circulation had ceased, tissue rebound was minimal and the blood urea concentration was relatively constant.
Assessing the formula for predicting 30 min urea
The 5 min post-dialysis arterial sample (A300) was used to estimate 30 min urea using the prediction formula. Estimated 30 min urea was then used to generate the urea reduction ratio (URR) and Kt/V. These values were compared with results generated from measured 30 min urea. The formula used for predicting 30 min urea was:
URR was calculated using the formula below:
in which Ureapost is post-dialysis blood urea concentration and Ureapre is the pre-dialysis blood urea concentration [8,9].
Equilibrated Kt/V was calculated using either measured or estimated 30 min urea with the following single pool formula:
where t = time in h; R = post-urea/pre-urea; UF =ultrafiltration (l); and W = post-dialysis weight (kg) [5]. This value for equilibrated Kt/V assumes that tissue rebound is complete by 30 min and that a sample at this time therefore represents equilibrated post-dialysis urea within the patient.
Measurement of blood urea concentration
Blood urea concentrations were measured by the kinetic urease method (Sigma Chemical Co. Ltd) on a Bayer Advia 1650 analyser (Au 5200). For each dialysis session, all samples were analysed in the same batch. The coefficient of variance (CV) for serum urea at the prevalent concentrations in the study was 3.4% for between runs and 0.8% within runs at Monklands Hospital. At Crosshouse, the analyser runs continuously and the within-run CV was quoted as 2.4%. For each patient, all of the post-dialysis samples were analysed together in the same batch.
Statistics
Results are expressed as the mean±SD or median with inter-quartile range. Statistical comparison of post-dialysis urea was by MannWhitney test using Minitab for Windows v14.
Ethics
Ethical approval was obtained from the local research and ethics committee and all patients gave informed written consent.
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Results
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Fourteen patients from two renal units were studied. This represents all the available patients on HDF in both of these units. The demographics of the study population are shown in Table 1. This shows a wide range of dialysis delivery in terms of mean duration of dialysis (4.75±0.32 h), mean fluid removal (3.29±0.92 l), mean blood flow rate (375±65.82 ml/min) and urea clearance (5 min URR 67.62±4.74%).
Figure 1 shows the urea concentration in serial samples from the arterial port expressed as a fraction of the contralateral arm time0 urea. This figure demonstrates that the timing window is similar to that for standard HD patients, i.e. there is very little change in blood urea levels between 4 and 6 min post-HDF.

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Fig. 1. Mean arterial blood urea concentration after stopping dialysate flow expressed as a fraction of blood urea concentration of the contralateral arm at time zero vs time (n = 14).
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There were no significant differences between the median urea concentrations in A0 and A240, A300 and A360. However, when post-dialysis urea was expressed as a percentage of the contralateral arm at time0, there was a significant difference when the median value immediately post-dialysis was compared with the median values at 240, 300 and 360 s (88.73 vs 97.18%, P = 0.0001; 97.33%, P = 0.0001; 96.93%, P = 0.0006, respectively).
Table 2 shows the measured urea, urea rebound, URR, and single pool Kt/V at 0, 5 and 30 min. Rebound is expressed as a percentage of blood urea immediately post-dialysis. In the current study, 50% of the total 30 min rebound takes place in the first 5 min and the total mean rebound over 30 min was 20.63±9.62%. This is similar to the level of post-dialysis urea rebound that has been reported for standard HD [4,10,11].
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Table 2. Measured urea, urea rebound, URR, and single pool Kt/V at 0, 5 and 30 min using blood from the arterial circuit
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The relationship between measured 30 min post-dialysis urea and estimated 30 min post-dialysis urea concentration was determined using a simple scatter plot (Figure 2) and the method of Bland and Altman [12] (Figure 3). The scatter plot in Figure 2 demonstrates clearly the close relationship between measured and estimated 30 min blood urea (R2 = 96%). However, a scatter plot might be expected to show a close relationship between measured and estimated urea as both the measured and estimated values are based on the same measured value for urea and are therefore intrinsically linked. To assess better the performance of the prediction equation, a BlandAltman plot was created. In this plot, the difference between the estimated and measured value for each patient is plotted against the average of the measured and estimated 30 min post-dialysis urea concentration. Plotting the difference against the average of measured and estimated values has been shown to be preferable simply to plotting the difference against the measured value [13]. The difference between estimated and measured urea concentration is expressed in mmol/l; positive values indicate that the prediction equation overestimates the 30 min urea concentration and negative values indicate underestimation of the 30 min urea concentration. Overall, there is a tendency for the prediction equation to overestimate the 30 min urea value. The median value for overestimation was 0.23 mmol/l [interquartile range (IQR) 0.0740.374].

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Fig. 2. Measured 30 min post-dialysis urea against estimated 30 min urea (mmol/l). Estimated 30 min urea is derived using the linear regression equation 30 min urea = (1.06 x 5 min urea) + 0.22. A line of identity is shown by the dotted line.
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Fig. 3. BlandAltman plot of the difference between estimated and measured 30 min post-dialysis urea (mmol/l) against the average of measured and estimated 30 min post-dialysis urea. Positive values occur when the regression equation has overestimated the 30 min post-dialysis urea. The 95% confidence intervals are shown with dotted lines. The regression line is also shown.
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Measured URR and Kt/V were plotted against estimated URR and Kt/V (Figures 4 and 5, respectively), and these plots were used to calculate specificity, sensitivity, and positive and negative predictive values at different definitions of adequate dialysis.

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Fig. 4. Scatter plot of measured 30 min URR against estimated 30 min URR (n = 14). This graph also demonstrates specificity, sensitivity, and positive and negative predictive values when adequate dialysis is defined as URR 65%.
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Fig. 5. Scatter plot of measured 30 min Kt/V against estimated 30 min Kt/V (n = 14). This graph demonstrates specificity, sensitivity, and positive and negative predictive values when adequate dialysis is defined as Kt/V 1.2.
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Figure 4 shows measured 30 min URR against estimated 30 min URR and shows sensitivity and specificity when adequate dialysis is defined as >65%. Figure 5 shows measured 30 min Kt/V against estimated 30 min Kt/V. A measured 30 min sample has been used in the single pool equation as a gold standard by several authors as it is felt that most of the tissue rebound has occurred by then [7,11,14]. Accordingly, sensitivity and specificity are calculated using a definition of adequacy as >1.2 in keeping with the current DOQI guidelines [15,16]. These plots demonstrate that for both URR and Kt/V, the prediction equation is both highly specific and sensitive, and has high positive and negative predictive values.
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Discussion
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As HDF becomes more commonly used, the need to validate current methods of assessing dialysis adequacy becomes more important. This work has shown that a post-treatment arterial sample at 5 min using the SDF method can be extended to those patients receiving HDF as well as those receiving standard HD. The work in this study has demonstrated that the previously published prediction formula can be used to estimate 30 min blood urea accurately when used with a 5 min post-HDF sample. Thus the SDF method and the prediction equation can be used with a high degree of accuracy to allow calculation of 30 min or equilibrated Kt/V and URR in patients receiving either HD or HDF.
It is surprising that the level of clearance is not higher given the prescription of HDF. The median URR (using 5 min arterial urea) was 66.92% (range 64.1571.47) and the median Kt/Vsp (using 5 min arterial urea) was 1.33 (IQR 1.221.50). A median time of 4.75 h (range 4.55.0) with a median blood flow of 400 ml/min (range 312.5450) would be expected to deliver a greater degree of clearance. There is no obvious explanation for this observation. Although the convective component of HDF favours improved middle molecule clearance, there will also be improved urea clearance. Certainly most of the patients were transferred to HDF as they were not achieving adequate urea clearance with standard dialysis. Another possibility at least in terms of explaining the relatively low Kt/V is the rather high average weight of the patients in the study, where the average weight of 98.98±22.76 kg is heavier than expected for a typical HD patient. It is generally accepted that it is more difficult to achieve adequate urea clearance in heavier patients and it must be remembered that all patients available for analysis were included in this study. It would therefore appear that our study population is typical of patients being transferred to HDF and can therefore be said to be representative of patients receiving HDF.
That the total mean and median rebound is not greatly different from that seen in standard dialysis is perhaps not too surprising. Either the concentration gradient between body compartments is similar to standard dialysis or any potential for a greater concentration gradient as a result of more efficient dialysis is offset by greater haemodynamic stability and thus better perfusion of all tissue compartments. That HDF might confer a haemodynamic benefit over standard HD remains a controversial issue and, although there is some support for it from small case series, many of these studies have not allowed for other factors when comparing HDF directly with HD [17]. For example, it has been suggested that the majority of the haemodynamic benefit of HDF can be attributed to the cooler temperature within the extra-corporeal circuit in HDF [18]. The median volume of total ultrafiltration of 3.64 l (IQR 3.003.91) is rather high. High volumes of ultrafiltration can lead to underperfusion of peripheral tissues that in turn can increase tissue rebound post-dialysis [19]. The relatively high volume of ultrafiltration per session in this study does not appear to have led to any meaningful change in measured urea rebound possibly because the total ultrafiltration as a percentage of body weight was not that high (median ultrafiltration as percentage body weight = 3.45%, IQR 2.724.03).
Two patients received HDF via a central venous catheter, with the rest receiving HDF via a peripheral arterio-venous fistula. We have not examined whether there were any difference in rebound between these two groups of patients. The main difference between these two modes of access is that a blood sample from a central venous catheter is not prone to the dilutional effects of cardio-pulomonary re-circulation unlike an arterio-venous fistula. However, the effect of cardio-pulmonary re-circulation will have ceased within 2 min post-dialysis. Therefore, a 5 min blood sample using the SDF method will allow for cardio-pulmonary re-circulation whether it occurred or not.
Figure 3 and Table 3 demonstrate that there is a trend for the prediction equation to overestimate 30 min urea by 0.2 mmol/l on average. There was also a slight trend for this effect to be minimized at higher levels of post-dialysis urea although the R2 was only 1.4%. The mean rebound of urea in the study population that was used to generate the prediction equation was higher than that reported in the current study (27.3 vs 20.63%, respectively) [4]. Thus, the measured 30 min urea in this study was slightly lower than expected. The effect of this on subsequent 30 min URR and Kt/V is shown in Table 3 where URR is underestimated by an average of 1% and Kt/V is underestimated by 0.04 on average. This underestimation of dialysis delivery is not large and at least ensures that patients will be receiving adequate dialysis.
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Table 3. The 30 min urea, urea reduction ratio and Kt/V compared with the estimated 30 min urea, urea reduction ratio and single pool Kt/V
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We have not studied post-dialysis venous sampling in this study. We did set out to examine venous sampling but found that the sampling port was too close to the venous drip chamber. As a result, blood was being aspirated from this chamber, leading to dilution of the blood and falsely low urea levels.
The number of patients studied was small but typical of similar studies in this field. The methodology is labour intensive for researchers and subjects. Also, patients are understandably reluctant to extend the dialysis session by 30 min. We are confident that the data are sufficient to support the conclusions. The correlation between the 5 min post-HDF sample in the arterial lumen and the time0 sample from the contralateral arm is very close. Also, the prediction formula was shown to estimate 30 min urea and subsequent 30 min URR and Kt/V with a high level of accuracy, particularly for identifying those patients who are achieving adequate dialysis as defined as URR >65% or Kt/V >1.2.
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Conclusions
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This study has demonstrated that 5 min sampling using the stop dialysate flow method is a valid method of post-dialysis urea sampling in patients receiving three times a week HDF provided that a 5 min sample from the arterial side of the HDF circuit is used. Furthermore, in the setting of three times a week HDF, 30 min urea and thus equilibrated Kt/V and URR can be predicted accurately using the previously published prediction formula.
Conflict of interest statement. None declared.
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Received for publication: 19. 1.05
Accepted in revised form: 22. 6.05