Inter-dialytic variations in blood volume and total body water in uraemic patients treated by dialysis

Ezio Movilli, Giovanni C. Cancarini, Silvia Cassamali, Corrado Camerini, Giulio Brunori, Camilla Maffei and Rosario Maiorca

Division of Nephrology, School of Medicine, Spedali Civili and University of Brescia, Brescia, Italy

Correspondence and offprint requests to: Ezio Movilli, MD, Division of Nephrology, Spedali Civili, P. le Ospedale Civile 1, 25123 Brescia, Italy. Email: eziomov{at}libero.it



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. An optimal balance of sodium and water is one of the most important goals of haemodialysis (HD) therapy. However, while inter-dialytic variations in blood volume (BV) have been well described, very little is known about the dynamics of fluid accumulation and distribution in body compartments during the inter-dialysis period.

Methods. We studied inter-dialysis variations in BV, measured as percent variation of plasma haemoglobin (Hb) concentrations (%{triangleup}BV) and percent variation of total body water (%{triangleup}TBW), in 24 uraemic patients treated by standard bicarbonate dialysis. These parameters were determined at the end of the last weekly dialysis (T0), after 24 h (T1), 48 h (T2), and at the beginning of the following dialysis session (T3). At each time point we measured Hb, haematocrit (Hct), serum albumin (sAlb), plasma sodium (Na), plasma potassium (K), blood urea nitrogen (BUN), plasma osmolality (Osm), body weight (BW), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). All patients were clinically stable and had no evidence of acute blood loss in the 3 weeks before the study.

Results. During the inter-dialysis period, there were increases in BUN, K and Osm, but Na did not change. SBP and DBP also did not change. HR tended to decrease, and showed a significant reduction between T0 and T3. TBW increased in a linear fashion whereas BV increased exponentially, showing a slow rise during the first 24 h followed by a greater increase in the following time intervals. This was confirmed by concomitant but opposite percent variations in Hct and sAlb concentrations.

Conclusions. Despite the limitations of the current methodology, our data show that the increase in TBW is redistributed during the long inter-dialysis period and this may prevent the effects of a too premature expansion of the intra-vascular compartment. This is especially evident during the first 24 h after HD, during which %{triangleup}BV is lowest, indicating a preferential distribution of the fluid load towards the extra-vascular space. During the following time intervals, the extra-vascular compartment refills in conjunction with an exponential expansion of BV that reaches its maximum in the last 24 h before HD.

Keywords: blood volume; body weight gain; haemodialysis; inter-dialysis interval



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Chronic overhydration is a cause of high blood pressure (BP) in end-stage renal disease [1], and removal of salt and water by dialysis frequently improves or normalizes uraemic hypertension [2]. However, an excess of ultrafiltration during haemodialysis (HD) causes intra-dialytic hypotension during 10–30% of all dialysis sessions [3]. Moreover, long inter-dialytic periods result in a volume expansion observed at the beginning of HD that may cause under-estimations of haemoglobin (Hb) values and result in an over-correction of anaemia with rHuEPO therapy [4].

Because of the clinical importance of dialysis-associated hypotension, most previous studies examining variation and distribution of body fluids were performed during HD treatment [5]. In contrast, very little is known about mechanisms of body fluid accumulation and distribution in the different body compartments during the inter-dialytic period.

The aim of this study was to evaluate variations in blood volume (BV) and total body water (TBW) during the long inter-dialysis period in a group of 24 stable uraemic patients treated by dialysis; we also examined concomitant variations in BP, serum electrolytes and plasma osmolality (Osm).



   Subjects and methods
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
The participants in the study were 24 uraemic patients (18 men and six women), aged 62 ± 16 years (range 24–87 years), on regular long-term HD for a median of 55 months (range 13–338 months).

Selection criteria
All of the patients were treated by bicarbonate dialysis three times weekly with 1.4–1.8 m2 substituted cellulosic membranes. The median duration of the dialytic procedure was 240 min (range 180–270 min). The median blood flow rate was 300 ml/min (range 250–350 ml/min). The dialysate flow rate was 500 ml/min. Dialysate fluid composition was: sodium 140 mmol/l, potassium 2–3 mmol/l, calcium 1.5–1.75 mmol/l, bicarbonate 35 mmol/l, acetate 4 mmol/l and glucose 1 g/l.

The patients had been on long-term HD for at least 6 months, were treated with subcutaneous rHuEPO for at least 4 months at a dose of 98 U/kg/week, and had stable Hb levels that were targeted between 11 and 12 g/dl for at least 3 months prior to the study. All of the patients were anuric or very oliguric (daily urine volume <100 ml/24 h), did not complain of dialysis hypotension, and were clinically stable with no evidence of acute blood loss in the 3 weeks before the study. Of the 24 patients, 17 received antihypertensive therapy (calcium channel blockers and/or beta blockers). The underlying renal diseases were: chronic glomerulonephritis in 10 patients, tubulointerstitial nephritis in one patient, nephroangiosclerosis in two patients, diabetic nephropathy in two patients, polycystic kidney disease in two patients, and undiagnosed nephropathy in seven patients.

Study protocol
Patients were studied during the long inter-dialytic interval. They were asked not to change their normal dietary habits and not to alter their usual therapy.

Measurements were taken at the end of the final dialysis for the week (T0), after 24 h (T1), after 48 h (T2), and at the beginning of the next dialysis (68 h), which was the first of the following week (T3).

At each time point, we measured Hb, haematocrit (Hct), serum albumin (sAlb), plasma sodium (Na), plasma potassium (K), blood urea nitrogen (BUN), plasma Osm, body weight (BW), systolic BP (SBP), diastolic BP (DBP) and heart rate (HR), percent variation in BV (%{triangleup}BV), and percent variation of TBW (%{triangleup}TBW).

After 15 min of quiet sitting, BP was determined using a mercury sphigmomanometer. The first and fifth Korotkoff sounds were used to identify SBP and DBP, respectively. Then, blood was drawn from an antecubital vein in the controlateral arm from the AV fistula. In addition, patients dressed in a similar fashion were weighed at each of the time points (T0–T3) using a bed balance having a scale of 0.05 kg (Tassinari, Cento, Italy). Hb and Hct were measured using a Coulter counter (Coulter Electric, Hialeah, FL), sAlb by a nephelometric assay, BUN, Na and K by an autoanalyser (Olympus AU 560; Olympus Italia, Segrate, Milan), and plasma Osm was determined using an Advanced Cryomatic Osmometer (Advanced Instruments, Norwood, MA).

Calculations
The %{triangleup}BV and %{triangleup}TBW were measured as follows.

TBW at T0 was determined using the equation by

Watson et al. [6]:

Males: 2.447 - (0.09516 x age) + (0.1074 x height) + (0.3362 x BW)

Females: -2.907 + (0.1096 x height) + (0.2466 x BW)

BW is expressed in kg, age in years and height in cm. The increase in BW during the inter-dialytic period was assumed to be a pure increase in TBW, such that each 1 kg increase in BW corresponds to a 1000 ml increase in TBW.

The %{triangleup}TBW was calculated according to the following equation:

where TBWt0 and TBWtx are TBW at T0 and the subsequent time points, respectively.

The %{triangleup}BV was calculated by analysing variations in Hb concentrations at each of the time points according to the following assumptions. (i) In the absence of acute haemorrhage and during very short periods of time, the total Hb mass is constant. (ii) During HD, the increase in Hb concentration is due to ultrafiltration and it is inversely proportional to the corresponding variations in BV. (iii) During the inter-dialytic period, the reduction in Hb concentration is due to BV expansion and these parameters are proportional to each other.

These same assumptions are used by on-line devices that measure inter-dialytic variations in haematic volume, and such devices are now widespread in clinical practice [7].

The %{triangleup}BV was calculated according to the following equation:

where Hbt0 and Hbtx are Hb concentrations at T0 and at the other time points, respectively.

Statistics
All values are expressed as means ± SD. Intra-group comparisons were made by paired Student's t-tests. Differences were considered significant at P < 0.05.



   Results
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 Subjects and methods
 Results
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 References
 
The values for Hb, Hct, sAlb, Na, K, BUN and Osm at T0–T3 are shown in Table 1. Both Hb and Hct significantly decreased between T0 and T3. However, these decreases were not linear, showing relatively modest reductions in the first 24 h, followed by progressively greater decreases in the following intervals. The same trend was also observed for sAlb concentrations. Plasma Osm, BUN and K all showed significant increases during the observation period. In contrast, Na did not significantly change.


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Table 1. Hb, Hct, sAlb, Na, K, BUN and sOsm during time periods T0–T3

 
Table 2 shows BW, TBW, SBP, DBP and HR at time periods T0, T1, T2 and T3. BW significantly increased during each interval of observation. The total increase in BW between T0 and T3 was 3.3 ± 0.6 kg. SBP tended to increase between T0 and T3 but this elevation was not significant. DBP did not change during the interval of observation. In contrast, HR showed a decreasing trend that became significant between T0 and T3.


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Table 2. BW, TBW, SBP, DBP and HR during time periods T0–T3

 
Figure 1 shows the %{triangleup}TBW and %{triangleup}BV during the three time intervals. There was a constant increase in %{triangleup}TBW (lower line) during the first 48 h (~3% for each interval of time), followed by a modest reduction in the rate of increase during the last observation period (%{triangleup}TBW T2–T3: 2.5 ± 0.1%). The basal TBW volume was 35.39 ± 6.38 l and the total %{triangleup}TBW between T0 and T3 was 8.4 ± 0.5%. The %{triangleup}BV (upper line) increased in a non-linear fashion throughout different observations periods. During the first 24 h (T0–T1), this variation was 2.6 ± 0.1%, at T1–T2 it was 4.3 ± 0.2%, and at T2–T3 it was 9.8 ± 1.2%. The total %{triangleup}BV between T0 and T3 was 17.4 ± 1.3%.



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Fig. 1. Percent variations of TBW and BV in the long inter-dialysis period.

 
Figure 2 shows the daily percent distributions of TBW and BV increases during the long inter-dialysis period. Compared with TBW, there was a relative saving of BV in the first 24 h, followed by an exponential increase in BV expansion in the following 48 and 68 h. TBW tended to expand constantly during the first 48 h, with a slight decrease in the last pre-dialysis period.



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Fig. 2. Daily percent distributions of TBW and BV increases during the long inter-dialysis period.

 


   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
In the current study, we evaluated relative percent variations of BV and TBW during the long inter-dialysis period in a group of 24 stable uraemic patients undergoing dialysis. We found that BW progressively increased by ~1 kg/day in the first 48 h, but showed slight decreases during the last 24 h before the next HD session (Table 2). The total BW increase was 3.2 ± 0.6 kg, which is normal for HD patients with no residual renal function. In parallel with this, %{triangleup}TBW showed increases that slowed during the last period (Figure 1, lower line). In detail, %{triangleup}TBW during the first 48 h was ~3%, with a slight decrease in the final 24 h before the next HD, indicating that water and salt accumulation occurred gradually and linearly during the inter-dialysis period. Unlike %{triangleup}TBW, the rate of %{triangleup}BV was completely different (Figure 1, upper line), and showed an exponential increase during the same inter-dialysis period (2.6% increase during the first 24 h after HD, 4.3% increase during the following 24 h, and 9.7% increase during the last 24 h). These increases in BV were confirmed by concomitant but opposite percent changes in Hct and sAlb (Table 1), which because of their prevalent intra-vascular distribution show variations that are similar to changes in Hb. Moreover, the analysis of percent distribution of TBW and BV during the inter-dialysis period (Figure 2), confirmed differences between the two compartments, with a relative saving of BV in the first 24 h, compared with TBW, followed by progressive increases in percent BV that reached a maximum during the last 24 h before HD. To our knowledge, this is the first report of this kind of data. Previous authors suggested that the slow and gradual rate of TBW increase indicated a linear distribution among the different body compartments [8]. In contrast, our observations show that there is a non-linear division of fluids in spite of a linear increase in TBW during the inter-dialysis period. There are several possible explanations for this finding. Extracellular fluid expansion is known to be the most consistent finding associated with hypertension in uraemic patients [9]. However, results from studies in adults and children receiving HD have been contradictory. Some found that volume status affects inter-dialytic BP [10], while others failed to show such a relationship [11]. Although our patients tended to show an SBP increase, between T0 and T3 (Table 2), there was no relationship between SBP and %{triangleup}TBW. These findings are in accord with Luik et al. [12], who found that a 3 l inter-dialytic fluid load did not result in BP increases in most HD patients. The plasma volume contraction and negative sodium balance that occurs during HD may induce an increase in plasma catecholamines and a reduction in atrial natriuretic peptide levels [13]. Although we did not measure these substances, the progressive reductions in HR during plasma volume expansion in the inter-dialysis period indicate that compensatory sympathetic mechanisms in these patients were functioning normally.

Another important determinant of changes in body fluid is plasma Osm. In our patients, plasma Osm significantly increased during the inter-dialysis period. This increase was mainly due to elevations in BUN and K and not to a change in Na concentration. However, BUN affects Osm but not tonicity [14] because it has a low molecular weight with very high diffusibility. Therefore, it does not affect water distribution between the different compartments, except during rapid concentration changes such as during HD. In this respect, it is possible that some degree of rapid BV change does occur immediately after HD treatment due to post-HD refilling. Recently, Bellizzi et al. [15] evaluated changes in Hb immediately after HD, at 120 min and after 24 h. They found no difference in Hb concentrations from 120 min to 24 h despite a weight gain of ~1.6 kg. This indicates that post-dialysis BV refilling is almost complete after 120 min and that once the intra-vascular space has been refilled, fluid redistribution is directed mainly toward the interstitium to reconstitute the fluid space contiguous to vessels. This latter effect is probably due to a low total tissue compliance associated with a lesser degree of hydration of the tissues.

Despite the limitations of the present methodology, our data taken together suggest that TBW is redistributed during the long inter-dialysis period, and that this may prevent the effects of a too premature expansion of the intra-vascular compartment. This is mostly evident during the first 24 h after HD, during which TBW increases constantly but the percent increase in BV is lowest, indicating a preferential distribution of the fluid load towards the extra-vascular space. During the following time intervals, the extra-vascular compartment refills, accompanied by an exponential expansion of BV that reaches its maximum in the last 24 h before the next HD. These data suggest the clinical implication that more frequent HD sessions, such as daily HD sessions, may provide more adequate prevention of excessive BV expansion and cardiovascular overload.

Conflict of interest statement. None declared.



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 15. 2.04
Accepted in revised form: 16. 7.04