Assessment of haemodialysis adequacy by ionic dialysance: intra-patient variability of delivered treatment
Christopher W. McIntyre,
Stewart H. Lambie,
Maarten W. Taal and
Richard J. Fluck
Department of Renal Medicine, Derby City General Hospital, Derby, UK
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Abstract
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Introduction. Adequate delivered dose of solute removal (as assessed by urea reduction and calculation of Kt/V) is an important determinant of clinical outcome in chronic haemodialysis (HD) patients. The requirement for multiple blood sampling and efforts taken to minimize the effects of rebound on post-treatment samples ensure Kt/V is measured only intermittently. On-line conductivity monitoring (using sodium flux as a surrogate for urea) allows the repeated non-invasive measurement of Kt/V on each HD treatment. We have studied the accuracy of this method of measuring Kt/V, and the variability of treatment dose delivered to individual patients.
Methods. We prospectively studied 26 established chronic HD patients over 4 weeks (316 treatments). Patients were dialysed using Hospal Integra dialysis monitors, equipped with Diascan® modules to measure Kt/V. Data were downloaded automatically to a central computer server. Urea reduction was measured (once a week) by a two-pool calculation using 30 min post-treatment sampling.
Results. Treatment time, QB and modality were fully delivered in all treatments analysed (97% of total). Kt/V measured by ionic dialysance (Kt/VID) correlated highly with that derived from measurement of urea reduction (R2=0.92, P<0.0001). Kt/VID underestimated urea-based Kt/V by a mean of only 1.5% (95% CI 0.182.9%). Kt/VID varied greatly within individual patients with a mean CV of 0.13±0.10 (95% CI 0.050.3). If a Kt/VID of 1.0 is considered adequate, 55% of the patients had variations that would have potentially altered their status as being adequately or inadequately dialysed, as the range of Kt/V readings cross that point during the study period.
Conclusion. In conclusion, Kt/VID seems to be an accurate and readily obtained measure of adequacy. Substantial variation in Kt/V implies repeated measures (ideally for all treatments) are necessary to gain a true picture of the mean treatment dose being delivered to patients.
Keywords: haemodialysis; Kt/V; ionic dialysance
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Introduction
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It is now well recognized that at an adequate delivery of haemodialysis (HD) dose (as measured by Kt/V derived from urea reduction) is a crucial determinant in clinical outcome of chronic HD patients [13]. This requires both prescription of an adequate dose of HD and regular assessment that the delivered treatments are also adequate [4,5].
There are many reasons why a discrepancy between calculated and delivered dose of extra-corporeal blood purification might exist. Failure of staff to ensure the pre-determined treatment time is given (usually in the face of variable patient resistance) is a common failing. However, other factors such as suboptimal needle placement, haemodynamic instability and progressive access malfunction all militate against this optimal delivery [6]. Monitoring of Kt/V requires blood sampling both before and after HD. The logistical problems with this in combination with the inconvenience of measures taken to reduce the effect of post-dialytic rebound in serum urea ensure that this is an infrequently taken measure in the vast majority of chronic HD units. NKF-DOQI guidelines recommend a monthly interval (given as a pragmatic rather than ideal recommendation). There are some data available to suggest that considerable variation occurs in delivery of treatment dose on a session to session basis [5,7].
Recently, advances in the on-line monitoring of conductivity during HD sessions have made the repeated measurement of Kt/V on all HD treatment sessions a practical proposition [810]. The measurement of ionic dialysance by the use of a second conductance probe in the dialysate waste and regular set perturbations of inlet dialysate conductivity enables the software to measure the movement of ions across the dialysis membrane. The ions of quantitative importance (largely sodium) have similar transfer characteristics to urea. This allows the depurated volume to be measured at 30 min intervals throughout dialysis, and Kt/V to be recorded [8]. This method has been shown to have an excellent correlation with Kt/V measured by urea reduction in a number of small studies [810].
The aims of this study were to further compare Kt/V measured by ionic dialysance (Kt/VID) with Kt/V calculated from urea reduction. Furthermore, using the repeated measures of Kt/VID we planned to investigate the degree of variation in delivered Kt/V that a group of stable chronic HD patients might be subjected to.
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Subjects and methods
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Patients
We prospectively studied 26 (21 male, five female) stable chronic HD patients for a 4 week period (316 treatments in total). In summary, all patients had been on HD for >1 year [mean 14.8±3.2 (range 1247) months]. Mean age was 61 years (range 2678 years). All patients were oliguric and 16 were anuric. It was assumed therefore that none of these patients still possessed any meaningful degree of residual renal function. All patients were dialysing using two needles in native arteriovenous fistulae. No changes were made to any of the dialysis prescriptions over the study period. Patients were appropriately consented. All patients were studied within the main HD unit at Derby City Hospital.
Haemodialysis schedule
HD was performed using Hospal Integra® dialysis monitors, equipped with Diascan® conductivity monitoring modules. All patients dialysed for 4 h treatment sessions, three times per week. Ultra pure dialysate was generated using water having undergone dual pass treatment. Patients were dialysed using haemophan dialysers (Hospal HG 500-700), bicarbonate buffering and a dialysate sodium concentration of 140 mmol/l (QD 500 ml/min). There were no variations to blood pump speeds during the duration of the study. Dialysis prescriptions were held on a separate server and downloaded to the patient for each treatment. All treatments were monitored for changes in relative blood volume, by the use of continuous measurement of haemoglobin concentration (Hemoscan®). All data pertaining to the dialysis session were uploaded to patient specific files at the end of each treatment for subsequent analysis.
Measurement of dialysis adequacy
Kt/V was measured by two techniques. Ionic dialysance and effective plasma conductivity is measurable by a standard module available on the Hospal Integra dialysis monitor (Diascan®). The Diascan module changes inlet conductivity every 30 min and records the change in conductivity at a second conductance meter at the dialysate waste. From this change ionic dialysance and plasma conductivity can be calculated automatically. Because conductivity is related to ion concentration it is possible to substitute one for the other in further calculations. Because the transfer characteristics of sodium and urea are similar, the ionic dialysance reflects the clearance of urea (corrected for recirculation). Kt/VID is calculated automatically by the dialysis monitor, having measured depurated volume (Kt). The value for V however must be calculated and entered seperately. Ionic dialysance derived Kt/V (Kt/VID) has been validated as an effective and accurate system for the assessment of dialysis adequacy (as measured by Kt/V) [8,10].
The 316 treatments that were studied using Kt/VID were supplemented by weekly collection of pre- and post-dialysis serum samples, to measure urea reduction (112 measurements in total). Post-dialysis samples were taken after 30 min to allow for full equilibration. Kt/V was calculated using the Daugirdas equation (second generation) [16]. V was calculated after Watson [17].
Statistical analysis
All data were analysed using GraphPad Prism version 3.00 for Windows (GraphPad Software, San Diego, CA, USA; www.graphpad.com). Correlation plots were subsequently analysed by linear regression. Coefficient of determination was calculated from the Pearson correlation. Intra-patient variability was assessed by calculation of CV coefficient data and are expressed as mean±SEM (95% CI) unless otherwise stated.
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Results
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Ninety-seven per cent of the 316 treatments resulted in the full-prescribed dialysis prescription being delivered (in terms of two needle, dialyser size, QB and treatment time and reduction of RBV by at least 5%). Only data from these treatments were subsequently analysed. Mean blood pump speed of the analysed treatments was 267±35 (216302) ml/min.
Mean Kt/V was 1.13±0.02 (1.091.18) as measured by urea reduction and 1.1±0.02 (1.061.14) as measured by ionic dialysance. The small difference between these two values did reach statistical significance (P=0.02). There was an excellent correlation in Kt/V as assessed by both methods (R2=0.92, P<0.0001) (Figure 1A
). Kt/VID underestimated urea reduction based on Kt/V by a mean of only 2.54% (95% CI 0.854.2%) (Figure 1B
) (Kt/VUREAKt/VID/mean of both measurements expressed as a percentage). There was a high degree of precision between the two measures as illustrated by BlandAltman plot (Figure 1B
).

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Fig. 1. Correlation between Kt/V as measured by urea reduction and by ionic dialysance, R2=0.92, P<0.0001. Kt/V as measured by urea reduction (112) and by ionic dialysance (264) in 26 patients.
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There was considerable variation in both delivered Kt/VID and Kt/V (measured by urea) within individual patients (Figure 3
). The mean coefficient of variation within individual patients was 0.13±0.10 (0.050.3) for Kt/VID and 0.11±0.01 (0.090.12) for Kt/V measured by urea. There was no statistically significant difference between the CVs, from either method. The distribution of CV across the 27 patients is illustrated in Figure 2
, for Kt/V measured by both methods. If a theoretical level of adequate dialysis was set at 1.0, then 55% of the patients studied had variation within the 1 month study period that, depending on when a single Kt/VID had been measured, their status as adequately or inadequately dialysed could have been altered (Figure 3
).

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Fig. 3. Kt/VID (A) and Kt/VUREA (B) of the 26 individual patients over the 4 week study period [with reference line of an adequate (equilibrated) Kt/V of 1.0].
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Fig. 2. Histogram of the distribution of CV for delivered Kt/VID (A) and Kt/V as measured by urea reduction (B), in individual patients.
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Discussion
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This study confirms the clinical usefulness of utilizing continuous online conductivity monitoring to assess the delivered dose of blood purification in chronic HD patients. The ability to assess Kt/V on each treatment also gives some insight into the significant variability of delivered dose that each individual patient is subjected to.
The high degree of correlation of Kt/VID, urea clearance [8,11] and Kt/V (measured from serum urea reduction is consistent with previously published data (all in small numbers of patients [1013]). All these studies also demonstrated a small underestimate of Kt/V when measured by ionic dialysance. We also found a slight underestimate. This has been postulated to be as a result of the effect of cardiopulmonary recirculation. Indeed recent data from Mercadal et al. [14] have shown a reduction in this slight difference in the absence of cardiopulmonary recirculation. The correlation between the two methods of assessing Kt/V has been reported to be poorer at the higher end of the spectrum (Kt/V >1.5) [8]. Treatments resulting in such high Kt/V were poorly represented in our study. The use of ionic dialysance to measure Kt/V is highly dependent on the assumptions made for V. This is especially important if patients have been subjected to inadequate removal of fluid and are significantly over hydrated at the end of dialysis. This was minimized within this study as all patients underwent relative blood volume measurements and this confirmed absolute reduction of RBV >5% in all treatments included in the analysis. Furthermore, the CVs of Kt/V derived by either method were not significantly different and demonstrated a similar inter- and intra-patient variability. The calculation of Kt/V using the second generation Daugirdas equation does not require entry of an assumed V value.
The use of Kt/VID allowed the study of intra-patient variability of delivered Kt/V. There are many factors that result in sub-optimal delivery of prescribed dialysis dose, including treatment time, vascular access function, number of needles inserted, haemodynamic stability and blood pump speed [15]. The variation in delivery of dialysis dose was significant in over half of the patients studied, even though treatments with inadequate dialysis time, needle placement (number of needles) and blood pump speed were all excluded. The full exploration of the reasons for such observed inter-treatment variability was beyond the scope of this initial study. However, such significant intra-patient variability has been noted in other studies using urea-based Kt/V. Arrigo et al. [7] noted such variation with haemodiafiltration, and attributed some of the change to variation in protein intake. It seems unlikely that these stable patients in our study did subject themselves to such large changes in their protein intake, given their stability in other aspects of treatment compliance (fluid gains, potassium and phosphate control). Kloppenburg et al. [5] undertook multiple assessments of Kt/V using serum urea reduction. This study concluded that multiple measurements were necessary to produce an averaged delivered dose and that basing clinical decisions of dialysis prescription on a single (usually monthly) URR or urea-based Kt/V was an unjustified practice and should be abandoned. Our data show that the use of Kt/VID affords a convenient and reliable method of fulfilling this ideal. In our study not only was there significant variation within many individual patients, but also the spread of delivered Kt/V would have resulted in up to half of the patients being potentially misclassified as adequate, or inadequate in terms of their dialysis adequacy (using an equilbrated Kt/V of 11.05).
In conclusion, Kt/VID appears to offer a reasonable level of accuracy and precision when compared with Kt/V measurements derived from serum urea reduction, sufficient to be useful in regular clinical practice. The current recommendation of intermittent assessment of urea removal is justified on both a pragmatic basis and its consistence with currently available data on dialysis adequacy and patient outcomes. The significant degree of variability in delivered Kt/V in regular clinical practice would suggest that only an averaged delivered measure of urea removal (as delivered by on-line conductivity monitoring) allows adequate assessment of actually delivered chronic HD treatment.
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Appendix
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Second generation Daugirdas formula [16]: Kt/V=Ln (R0.008xt)+(43.5xR)xUF/W.
Watson formula [17]: males, V=2.4470.09156 Age+0.1074 Height+0.3362 Post-dialysis body weight; females, V=2.097+0.1069 Height+0.2466 Post-dialysis body weight.
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Notes
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Correspondence and offprint requests to: Dr C. W. McIntyre, Department of Renal Medicine, Derby City General Hospital, Uttoxeter Road, Derby, DE22 3NE, UK. Email: chris-mcintyre{at}lineone.net 
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Received for publication: 10. 7.02
Accepted in revised form: 28.10.02