| Abstract|| |
To evaluate the individualization of dialysate sodium (Na + ) concentration in hemodialysis (HD), we studied 40 stable chronic HD patients in a single-blind crossover design. They underwent 36 consecutive HD sessions with the dialysate Na + concentration set at 138 mmol/L, followed by 36 sessions of dialysate Na + set to match the patients average pre-HD plasma Na + levels. We multiplied the midweek pre-HD measured Na + by the Donnan coefficient of 0.95 (individualized Na + ). Pre-HD Na + dialysis sodium levels were nearly constant, with no variation between the two phases and a mean of 137.45 ± 2.04 mmol/L. Post-HD serum Na + was significantly higher during the standard phase (139.7 ± 2 mmol/L) than during the individualized phase (137.1 ± 1.6 mmol/L). Also, interdialytic weight gain (IDWG) was significantly more reduced during the individualized phase (3.25 ± 0.56%) than during the standard phase (3.94 ± 0.92%), P <0.001. Episodes of distressing symptoms including headache, muscle cramps and hypotension were significantly less frequent in the individualized phase. The mean of the pre-HD and post-HD systolic and diastolic blood pressures significantly decreased during the individualized phase, and we could reduce the doses of antihypertensive drugs in 10 (33.33%) patients. Individualized dialysate Na + concentration was associated with a decrease in IDWG and dialysis hypotension and related symptoms and better BP control in stable chronic HD patients.
|How to cite this article:|
Elshahawy Y, Sany D, Shawky S. Outcome of individualized dialysate sodium concentration for hemodialysis patients. Saudi J Kidney Dis Transpl 2013;24:507-13
|How to cite this URL:|
Elshahawy Y, Sany D, Shawky S. Outcome of individualized dialysate sodium concentration for hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2013 Dec 5];24:507-13. Available from: http://www.sjkdt.org/text.asp?2013/24/3/507/111025
| Introduction|| |
In many dialysis patients, dry weight is not reached because of an imbalance between the interdialytic accumulation of water and sodium (Na +) and the brief and discontinuous nature of routine dialysis therapy. Accumulation of water and Na + is the predominant factor in the pathogenesis of hypertension and left ventricular hypertrophy in hemodialysis (HD) patients. 
Manipulating the sodium concentration of the dialysate is an important method to improve water and Na + control in HD patients. Reducing the Na + concentration of the dialysate increases the diffusive removal of sodium, which may reduce thirst and interdialytic weight gain. However, reducing dialysate Na + impairs the refill of blood volume from the interstitium and intracellular compartment. 
On the other hand, a supraphysiologic dialysate Na + concentration is effective in preventing hemodynamic instability related to rapid osmolar shifts during HD. However, pre-HD plasma Na + concentration is constant in HD patients who seem to have individual osmolar set points.  Consequently, the use of a dialysate Na + concentration higher than plasma levels could contribute to an increase in the interdialytic fluid ingestion in the attempt to achieve this set point.  Thus, it is of great importance to find an adequate balance between removal of Na + and maintenance of intradialytic hemodynamics. Sodium dialysate concentration is usually set to a high concentration at the beginning of HD and gradually decreased afterwards, a procedure called Na + profiling.  However, little data exist in stable, non-hypotension-prone patients.  In these patients, higher dialysate Na + is often not necessary and may result in complications such as increased thirst, interdialytic weight gain (IDWG) and hypertension.  Lower dialysate sodium dialysis is well tolerated in patients undergoing high-efficiency dialysis. ,
We aimed from our study to investigate the short-term consequences of individualized dialysate Na + prescriptions based on pre-HD plasma sodium concentration on HD treatment parameters and complications.
| Methods|| |
We prospectively studied 40 patients on chronic HD for at least 12 months at our HD unit, National Institute of Urology and Nephrology, at Ain-Shams University, Cairo-Egypt. All patients were receiving thrice-weekly HD with volumetric dialysis machines (Gambro AK95), bicarbonate-based dialysate and polysulfone dialyzers. Patient data included demographics and dialysis duration. Loop and distal tubular diuretics were not routinely prescribed to patients, and their antihypertensive drugs were not modified. No specific instructions about salt restriction were given to the patients who had stable clinical condition, prescribed dry weight based on clinical background besides mean dialysis URR (60.6%) and residual daily urine output <100 mL/day. Diabetic patients were not included in the study in order to avoid possible effects of poor glucose control on measurements of plasma sodium. The study protocol was approved by the ethical committee of the Ain Shams University, and all subjects signed a written informed consent.
The standard dialysis prescriptions included blood flow 300 mL/min and dialysate flow 500 mL/min. The standard dialysate composition included bicarbonate 33 mEq/L, potassium 2.0 mEq/L, calcium 3.5 mEq/L, magnesium 1.0 mEq/L and chloride 109.5 mEq/L.
The study was performed in two different phases, with each subject used as his/her own control:
First or standard phase: Patients underwent three sessions of HD/week for 12 weeks. The dialysate sodium concentration was fixed at 138 mEq/L.
Second phase or individualized phase : Started immediately following the first phase, where the same patients were subjected to HD three times/week for another period of 12 weeks duration against the dialysate Na + concentration, which was calculated for each session by multiplying the midweek pre-dialysis measured Na + levels by the Donnan coefficient of 0.95 (individualized Na + ). The patients were not aware of the modification in the dialysate Na + concentration.
During the two phases of the study, the patients were subjected to the following:
- Blood pressure pre and post all HD sessions were measured using a mercury sphygmomanometer. Auscultatory mea surements followed standard clinical guide lines using Korotkoff I and V sounds to indicate systolic and diastolic BP, respec tively. Pre-HD BP of >160/90 mmHg or post-HD BP of >140/80 mmHg were used as thresholds for diagnosing hypertension because they had a specificity of at least 80% according to the criteria of Agarwal and Lewis. 
- Estimated dry weight was determined through standard clinical criteria. IDWG was also determined based on the changes of body weight between the end of the HD session and the return to the next session.
- Dialysis-related hypotension and symptoms (headache, cramps, nausea and vomiting) were recorded and analyzed as the number of occurrences during each study phase. Hypotensive episodes were defined as rapid changes in BP (within 30 min) accompanied by symptoms requiring nursing interventions or a brisk fall in BP >40 mmHg systolic or >20 mmHg diastolic within a 30-min period regardless of symptoms or interventions. 4. Blood samples were obtained pre and post the midweek HD session for Na + analysis using a direct ion selective electrode method (AVL 988-3; AVL medical instruments). Delta sodium (Δ Na) was calculated as the difference between the mean pre-dialysis Na+ concentration and the mean post-dialysis Na + measured on the midweek sessions.
| Statistical Analysis|| |
We used paired Student's t test to compare continuous variables between each study phase. Wilcoxon signed rank test was used instead of the paired t-test in non-parametric data. Pearson correlation coefficients and simple linear regression were used to study the relationship between the different continuous variables. P-values <0.05 were considered statistically significant. We used the statistical package SPSS/ PC (SPSS Inc., Chicago, IL, USA) for all calculations.
| Results|| |
Of the 40 study patients, 20 patients were males (50%), and the age ranged from 24 to 71 years, with a mean of 46 ± 14 years. Dialysis duration ranged from 13 to 180 months, with a mean of 31 months. The etiology of end-stage renal disease (ESRD) is shown in [Table 1]. The mean dialysate Na + concentration in the individualized phase was 131.4 ± 1.4 mmol/L.
The patients had a mean urine output of 58.3 ± 24.4 mL/day. The mean dry weight was 72.67 ± 18 kg, the mean urea reduction ratio (URR) was 60.6 ± 5.31% and the mean protein catabolic rate (PCR) was 0.83 ± 0.13. There were 30 (75%) patients with hypertension and 10 (25%) patients with normotension.
Pre-HD Na + serum levels were nearly constant with no variation between the two phases, with mean pre-HD serum Na + of 137.45 ± 2.04 mmol/L during the standard phase and 137.5 ± 2.1 mmol/L during the individualized phase. The coefficient of variation of the pre-HD sodium concentration was 1.4% and 1.5% during the standard and individualized phases, respectively. The post-HD serum Na + was significantly reduced from 139.7 ± 2 mmol/L during the standard phase to 137.1 ± 1.6 during the individualized phase. Also, the IDWG was significantly reduced during the individualized phase (3.25 ± 0.56% versus 3.94 ± 0.92% in the standard phase).
The episodes of distressing symptoms were significantly reduced in the individualized phase. There were significant differences in the occurrence of symptoms between the standard Na + and the individualized phases, respectively, regarding headache (45% vs 18%), muscle cramps (50% vs 30%) and hypotension (100% vs 38%), but the reduction in the episodes of nausea and vomiting was not statistically significant (25% vs 22%).
Blood pressure was significantly reduced during the individualized phase; this includes pre-HD systolic (pre-HD SBP), pre-HD dias-tolic (pre-HD DBP), post-HD systolic (post-HD SBP) and post-HD diastolic blood pressure (post-HD DBP), as shown in [Figure 1].
|Figure 1: Blood pressure in the individualized and standard phases of the study.|
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Of the 30 hypertensive patients, the doses of antihypertensive drugs were reduced in ten patients (33.33%), increased in only one patient (2.5%) and not changed in 19 (63.33%) patients. In addition, all the 30 hypertensive HD patients had lower pre-HD SPB, pre-HD DBP, post-HD SBP, post-HD DBP, pre-HD mean arterial blood pressure (MABP), post-HD MABP and IDWG on the individualized phase [Table 2].
In the standard phase, there was a significant positive correlation between post-HD serum Na + and IDWG and post-HD MABP. In addition, there was a significant negative correlation between Δ Na+ and post-HD MABP and a significant positive correlation between IDWG and pre-HD and MABP.
| Discussion|| |
In this study, we analyzed the short-term consequences of an individualized dialysate Na + prescription in a population of non-diabetic, non-hypotension-prone stable HD. The short-term duration permitted us to leave unchanged important parameters such as estimated dry weight and the dosage of vasoactive drugs, and link the observed differences exclusively to the dialysate Na changes. The main findings of our study were a reduction in IDWG and an improvement in pre-HD blood pressure in hypertensive patients.
The difference in Na + concentration between plasma and dialysate  occurs because plasma water constitutes only 93% of the total plasma, whereas it is 100% of the total dialysate volume. In vivo, this concentration difference is compensated by the Gibbs-Donnan effect. Otherwise, the dialysate should have a concentration approximately 6-7 mEq/L higher to result in an isonatremic dialysis. , . The Gibbs-Donnan effect in HD occurs because plasma proteins, which are negatively charged and not diffusible through the dialysis membrane, create an electric field that attracts Na + , reducing the plasma diffusible sodium by 4-5%. 
Our results showed that the pre-HD serum Na + concentration was nearly constant when the dialysate was set to a standard concentration (137.45 ± 2.04 mmol/L), and remained at the same level when the dialysate sodium concentration was individualized (137.5 ± 2.1 mmol/L). This is in agreement with previous studies showing that the pre-HD serum Na + concentration is constant, independent of the Na + gradient established between blood and dialysate in the previous session. , This fixed "osmolar set point," which is equal to the pre-HD serum sodium concentration, dictates the interdialytic fluid intake to reset osmolality; the higher the post-HD Na + , the greater the IDWG will be. ,
Post-HD dialysis serum Na + was significantly reduced from 139.7 ± 2 mmol/L during the standard phase to 137.1 ± 1.6 during the individualized phase. This is compatible with the results where there was a significant reduction of post-HD Na + from 135.9 ± 2.0 to 133.1 ± 2.6 in the individualized phase. 
Our results showed significant reduction of IDWG during the individualized phase versus the standard phase, and the same was observed by De Paula et al.  This can be explained by the net NA + gain in the standard phase.
In our study, there was a statistically significant reduction in systolic, diastolic and MABP in both pre-HD and post-HD measurements in the whole study patients and also in the hypertensive group during the individualized Na + phase. In contrast, Paula et al did not find a significant difference in blood pressure levels between the two phases of the study when analyzing the group as a whole.  However, stratified analyses according to BP control demonstrated that uncontrolled BP subjects had a significant improvement in BP control, whereas controlled BP patients remained with stable BP levels. This difference from the above study is probably caused by the short duration of the study, which was six weeks (three weeks for each phase); there is a well known "lag phenomenon" that states that correction of hypertension lags by a variable period of time behind reaching the dry weight. 
The main concern with the method of individualized dialysate Na + prescription is the development of hypernatremia and hypo-osmolality-related complications because of the lack of sodium diffusion and the concomitant sodium losses by ultrafiltration. However, we found that the episodes of distressing symptoms (headache, cramps and hypotension) decreased significantly in the individualized Na + phase. Indeed, the post-HD Na + plasma concentration was significantly reduced in the individualized Na + HD. However, convective sodium losses were lower than that expected in standard HD, and were partially compensated by the reduction in the ultrafiltration, and were well tolerated. Besides, pre-HD serum Na + remained unchanged despite the decrease in IDWG, probably related to a decrease in inter-dialytic fluid ingestion. Therefore, we believe that the adjustment in the sodium prescription based on pre-HD serum Na + levels may be used safely.
Our results showed that there was a significant positive correlation between post-HD serum Na + concentration and IDWG during the standard phase; high post dialysis serum Na + levels result in increased fluid intake to return plasma osmolality back to its set point. In the study by De Paula et al, there was a similar significant correlation between the dialysate to plasma Na + gradient and IDWG adjusted to the estimated dry weight (IDWG/DW%) in the standard dialysate Na + phase of the study.  Our data are also in agreement with the findings of Levin et al, who reported a significant correlation between the Na + gradient and the IDWG, showing that higher Na gradients were associated with larger IDWG. 
In our study, there was a significant positive correlation between post-HD serum Na + concentration and post-HD mean arterial blood pressure in the standard phase of the study (using Pearson correlation). Also, there was a significant negative correlation between Δ Na+ and post-dialysis MABP in the standard phase of the study. Similar findings were reported in the study of Levin et al, who demonstrated that higher Na + gradient was associated with a higher pre-HD MAP. 
Our results showed a significant positive correlation between IDWG and pre-HD MABP during the standard phase. From the previous data, we concluded that the significant reduction of blood pressure in the individualized phase was not related to change in Na + concentration, but could be due to the combined effect of decreased Na + diffusion from the dialysate and the decreased IDWG. Individualized dialysate prescriptions result in a decrease in ionic mass transfer to the patient,  with more favorable Na + balance and lower peripheral resistance, as has been suggested in patients undergoing daily nocturnal HD. ,
Our study has several limitations that merit discussion. First is the exclusion of hypotension-prone patients, which certainly limits the ability to generalize our results as discussed above. Second is the fact that we did not employ randomized block assignment to our study design, a technique that would have strengthened our methodology. Last is the fact that we did not use ambulatory BP monitoring, which is a more precise method to estimate BP in dialysis patients, as established by our own group. While this is a limitation, the careful protocol observed in the determination of peri-HD BPs makes our results as reproducible as possible.
We conclude that individualized dialysate Na + concentration was associated with a decrease in IDWG, dialysis hypotension and related-symptoms and better BP control in stable chronic HD patients. Long-term studies are necessary to observe whether these short-term benefits can be sustained.
Conflict of interest: No
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Division of Nephrology, University of Ain-Shams, Cairo
[Table 1], [Table 2]