Measurement of blood urea concentration during haemodialysis is not an accurate method to determine equilibrated post-dialysis urea concentration
Editor's note Please see also Editorial comment by Kooman et al. pp. 17491752.
Manuel Carlos Martins Castro,
João Egidio Romão, Jr and
Marcello Marcondes
Division of Nephrology, Hospital das Clínicas of the School of Medicine of São Paulo University, São Paulo, Brazil
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Abstract
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Background. The double-pool urea kinetic model requires the measurement of the blood urea concentrations 30 min after haemodialysis (Ct+30) to calculate equilibrated Kt/V. However, it has been suggested that urea concentrations 30 min before the end of dialysis (Ct-30) may be representative of Ct+30. The aim of this study was to validate this suggestion.
Methods. Twenty-two patients underwent haemodialysis for 180, 210, and 240 min. For each patient in each dialysis session, urea exponential decay curve was calculated. Because we measured Ct+30, we calculated the time (Tc) before the end of dialysis that blood urea concentrations would be the same as Ct+30. In an additional 33 patients, we measured blood urea concentrations at Tc and in Ct+30.
Results. We found that Ct-30 was significantly lower than Ct+30 independent of the duration of dialysis. However, there was a significant correlation between Kt/Vt-30 and Kt/Vt+30. The Tc was 45 min before the end of dialysis. In the additional 33 patients, Ct-45 and Ct+30 were 54±17 and 52±17 mg/dl (NS), and Kt/Vt-45 and Kt/Vt+30 were 1.27±0.21 and 1.29±0.18 (NS), respectively. There were significant correlations between Ct-45 and Ct+30 (r=0.96; P<0.001), and between Kt/Vt-45 and Kt/Vt+30 (r=0.82; P<0.001). However, when measurements were analysed individually, 48% of the data points from Ct-45 vs Ct+30, and 42% of the data points from Kt/Vt-45 vs Kt/Vt+30 fell out of the 95% confidence interval of regression line.
Conclusions. Although Ct-45 is useful to estimate Kt/V when assessing mean values, it is not suitable when assessing patients individually. This study demonstrates that the best method to calculate equilibrated Kt/V was a blood sample for urea concentrations 30 min after haemodialysis.
Keywords: equilibrated Kt/V; haemodialysis; intradialytic blood urea concentration; post-dialysis blood urea concentration; urea rebound
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Introduction
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Kt/V is the preferred method to assess dialysis therapy efficiency. It is measured using a two-sample method using pre- and post-dialysis blood urea concentrations. Therefore, Kt/V is highly dependent on the post-dialysis time at which blood urea is sampled. In the single-pool kinetic model, the urea sample taken immediately after dialysis overestimates the efficiency of haemodialysis because urea is distributed among different compartments, and redistribution of urea from these compartments is determined by variations in regional blood flow and the transcellular urea mass transfer coefficient [1]. This phenomenon results in a post-dialysis urea rebound created by diffusion of urea from poorly cleared compartments during dialysis [2]. Consequently, Kt/V depends on the extent to which the immediate post-dialysis urea sample (Ct) reflects the post-dialysis equilibrated urea concentration. In the double-pool urea kinetic model, an estimate of the equilibrated sample requires measurement of the blood urea concentration 3060 min after the end of dialysis [2,3]. However, this represents an additional burden for clinical practice.
In 1997, two studies demonstrated that urea concentrations 30 min before the end of dialysis (Ct-30) may be representative of the equilibrated post-dialysis urea concentration, which is 30 min after dialysis (Ct+30) [4,5]. The aim of the present study was to validate this observation.
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Subjects and methods
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Fifty-five patients with chronic renal failure on regular haemodialysis were included in this study after informed consent. The study population consisted of 32 men and 23 women, with a mean age of 33±12 years. Haemodialysis was performed using a Fresenius 2008D dialysis apparatus (Fresenius Corporation, Germany) and high-flux polysulfone haemodialyser, HF 60 or HF 80 (Fresenius Corporation, Germany). The dialysate flow rate was 800 ml/min using a bicarbonate buffer and the blood flow was 350 ml/min. All patients had arteriovenous fistula with native vein.
In the first phase of the study, 22 patients underwent three haemodialysis sessions with respective durations of 180, 210, and 240 min. In all dialysis sessions, blood samples were taken at the beginning (Co), 30 min before the end (Ct-30), and immediately after the end of dialysis (Ct). In addition, at least three additional blood samples were taken during dialysis to calculate the urea exponential decay curve. Thirty minutes after the end of haemodialysis, another blood sample was taken (Ct+30) to measure the equilibrated urea concentration. During haemodialysis, blood samples were taken from the arterial line 60 s after blood flow was reduced to 50 ml/min.
For each patient in each dialysis session we calculated the urea exponential decay curve for dialysis at 180, 210, and 240 min. Because we measured Ct+30, we calculated the time (Tc) before the end of dialysis at which blood urea concentrations would be the same as Ct+30.
In the second phase of the study, blood samples were taken from another 33 patients for urea concentrations at the beginning, at the calculated time (CTc), and 30 min after the end of dialysis. In these sessions, the treatment time was 210 min in 23 patients and 240 min in 10 patients.
Kt/V was calculated by the second-generation formula of Daugirdas [6] as follows:

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where: R=Ct/Co; t=dialysis duration (in hours); UF=total ultrafiltration volume (in litres), and Wt=post dialysis body weight (in kg).
For the calculation of Kt/V with the single-pool model, the Ct concentration was used, and for the equilibrated Kt/V in the double-pool model, Ct+30 was used. The equilibrated Kt/V was estimated from Ct-30 and CTc.
Results were expressed as means±standard deviation. Paired Student's t-tests and linear regression with Pearson's correlation coefficient were applied for statistical analysis. Data were further analysed using the method of BlandAltman [7]. A P value of <0.05 was accepted as the level of significance.
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Results
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Table 1
shows blood urea concentrations and Kt/V with single-pool and double-pool models from urea concentrations 30 min before and 30 min after the end of haemodialysis. Regardless of the duration of dialysis, Ct-30 value was always lower than Ct+30. Consequently, Kt/V calculated with Ct-30 was higher than Kt/V with Ct+30. Moreover, there was a significant correlation between Kt/Vt-30 and Kt/Vt+30 that was independent of the duration of dialysis (Table 2
). However, for the 180 min of haemodialysis, regression analysis between Kt/Vt-30 and Kt/Vt+30 showed that 23% of data points fell out the 95% confidence interval of regression line. For dialysis lasting 210 and 240 min, these values were 41 and 32%, respectively (Table 2
).
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Table 2. Correlation coefficient between Kt/V calculated with blood urea concentration 30 min before the end and 30 min after the end of haemodialysis
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After calculation of the curve of exponential reduction of blood urea concentration in each haemodialysis session, it was possible to determine CTc to estimate Ct+30. For dialysis lasting 180, 210, and 240 min, this time was 133±20, 163±21, and 194±17 min, respectively (Table 3
). In spite of the same mean blood urea concentration at 45 min before the end of dialysis (Ct-45) as Ct+30, the range of standard deviation, 20 min, was very large.
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Table 3. Calculated time of haemodialysis to estimate blood urea concentration 30 min after the end of haemodialysis
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In 33 additional haemodialysis sessions, blood urea samples were taken before dialysis (Co), 45 min before the end of dialysis (Ct-45), and 30 min after the end of dialysis (Ct+30). Blood urea concentrations were 149±32, 54±17, and 52±17 mg/dl, respectively. Kt/Vt-45 was 1.27±0.21 and Kt/Vt+30 was 1.29±0.18. The differences between Ct-45, Ct+30, and Kt/Vt-45, Kt/Vt+30 were not significant. Once again, there was a significant correlation between Ct-45 and Ct+30, r=0.96 (P<0.001), and between Kt/Vt-45 and Kt/Vt+30, r=0.82 (P<0.001). However, when measurements were analysed individually, about 16 (48%) data points of Ct-45, Ct+30 (Figure 1
) and 14 (42%) data points of Kt/Vt-45, Kt/Vt+30 (Figure 2
) fell out of the 95% confidence interval of regression line. Using the method of Bland and Altman, the mean difference between Kt/Vt-45 and Kt/Vt+30 was -0.02 with a range of -0.26 and 0.22 (mean±2 SD). Thus, although only one data point fell out the ±2 SD range, Kt/Vt-45 may be 0.26 below or 0.22 above Kt/Vt+30, a range that is unacceptable for clinical purposes (Figure 3
).

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Fig. 1. The relationship between blood urea concentration measured 45 min before (Ct-45) and 30 min after the end of dialysis (Ct+30) from 33 haemodialysis sessions.
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Fig. 2. The relationship between Kt/V measured 45 min before (Kt/Vt-45) and 30 min after the end of dialysis (Kt/Vt+30) from 33 haemodialysis sessions.
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Discussion
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In the single-pool model, urea is assumed to occupy a single distribution compartment. However, it has been shown that solute removal from plasma during haemodialysis is associated with an increase in blood urea concentrations after dialysis. This latter phenomenon is an expression of re-equilibration of the intercompartmental imbalance created by haemodialysis. Following this, retarded diffusion of urea produces rebound from a second pool that is poorly cleared during dialysis. Consequently, Kt/V calculated from blood urea concentration immediately after dialysis overestimates the effective haemodialysis efficiency [8].
It has been demonstrated that the urea rebound is complete 30 min after the end of haemodialysis in most patients [2,3]. However, the 30 min wait after the end of dialysis is inconvenient to both patients and care providers. Alternative methods were, therefore, proposed to estimate equilibrated Kt/V.
Smye et al. [9] suggested the use of a third urea blood sample (7090 min after haemodialysis onset) to calculate equilibrated post-dialysis urea concentrations. However, the mathematical calculation required may limit its clinical application. Two additional studies proposed that blood urea concentrations measured 30 min before the end of haemodialysis are equivalent to concentrations measured 30 min after dialysis [4,5]. However, these studies did not analyse the impact of treatment time as an independent variable.
Canaud et al. [4] studied patients on haemodiafiltration and showed a significant correlation between Kt/Vt-30 and Kt/Vt+30 (r=0.998). We found the same correlation, however, several data points fell out of 95% confidence limit of the linear correlation, suggesting that these methods may be not interchangeable (Table 2
).
Bhaskaran et al. [5] also observed a significant correlation between Kt/Vt-30 and Kt/Vt+30 (r=0.964), and using BlandAltman plots, they concluded that both methods might be interchangeable. However, we believe that in this study the differences amongst Kt/Vt-30 and Kt/Vt+30 and the range of the mean±2 SD were very large, suggesting once more that these methods are not interchangeable.
In the present study, urea concentrations measured 30 min before the end of haemodialysis were significantly lower than those measured 30 min after the end of haemodialysis. Moreover, this effect was independent of dialysis time. The blood urea concentration measured 30 min after the end of dialysis was 5% higher than when measured 30 min before the end of haemodialysis. Consequently, the equilibrated Kt/V was 5.6% lower than that calculated using blood urea measured 30 min before the end of dialysis. Although a significant correlation was obtained between these two values of Kt/V, which depended on dialysis duration (180, 210, and 240 min), 2341% of the data points fell out of the 95% confidence interval of regression line. Therefore, this method was not efficient for estimating equilibrated Kt/V in either situations. This was true when the results were assessed by the mean or individually.
Using the curve of blood urea reduction during haemodialysis, we found that blood urea concentrations 45 min before the end of haemodialysis estimated urea concentrations 30 min after dialysis, and this was independent of dialysis time. Therefore, using these values, the blood urea concentration and Kt/V were not statistically different in our study. However, although there was a significant linear correlation between Kt/Vt-45 and Kt/Vt+30 (r=0.82; P<0.001), 42% of data points fell out of the 95% confidence limit of the linear correlation. In addition, using the method of Bland and Altman suggested that the two values might not be interchangeable because the mean±2 SD range for the difference between Kt/Vt-45 and Kt/Vt+30 were very large. Therefore, although Ct-45 is useful to estimate equilibrated Kt/V when assessing mean values, it is not suitable when assessing patients individually.
In conclusion, this study indicated that the best method to calculate equilibrated Kt/V is the determination of blood urea concentration 30 min after the end of haemodialysis.
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Notes
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Correspondence and offprint requests to: Manuel Carlos Martins Castro, Rua Inhambu, 1069 Apto 72, CEP: 04520-013 São Paulo, Brazil. 
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References
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Received for publication: 4. 7.00
Revision received 19. 2.01.