| Abstract|| |
In order to reduce intradialytic and interdialytic morbidity, it is important to obtain a zero sodium balance at the end of each dialysis session. This can be achieved by matching exactly the interdialytic sodium and water intake with the intradialytic sodium and water removal. A positive sodium balance can be obtained by using hypernatric dialysis or "sodium ramping" or convective techniques. While reducing the intradialytic side effects (hypotension, cramps, nausea, vomiting), these methods may increase the interdialytic side effects (thirst, weight gain, hypertension and pulmonary edema). Given the highly variable amounts of sodium introduced during the interdialytic periods, the use of sodium-conductivity kinetic models allows removing exactly the amount of sodium accumulated in the interdialytic period. This strategy may be advantageous towards cardiovascular stability in patients prone to dialysis hypotension.
Keywords: Sodium balance, Sodium ramping, Kinetic model, Conductivity, Dialytic hypotension, Dialytic hypertension, Dialysis morbidity and mortality.
|How to cite this article:|
Locatelli F, Colzani S, D'Amico M, Manzoni C, Di Filippo S. Sodium Balance During Extra Corporeal Dialysis. Saudi J Kidney Dis Transpl 2001;12:345-51
|How to cite this URL:|
Locatelli F, Colzani S, D'Amico M, Manzoni C, Di Filippo S. Sodium Balance During Extra Corporeal Dialysis. Saudi J Kidney Dis Transpl [serial online] 2001 [cited 2020 Nov 26];12:345-51. Available from: https://www.sjkdt.org/text.asp?2001/12/3/345/33558
| Introduction|| |
There is still high incidence of intradialytic cardiovascular instability despite the continuous improvement of the dialytic methods and technology. This is mainly due to the progressive increase in the mean age of patients admitted to dialytic treatment and to the greater comorbid conditions negatively affecting their cardiovascular stability. Furthermore, there is a growing tendency to reduce the length of the dialytic sessions by increasing the dialysis efficiency and ultrafiltration rate.
Since sodium is the major determinant of volume and tonicity of the extracellular fluids, sodium balance is one of the main factors affecting cardiovascular stability.
Sodium crosses dialysis membranes by means of two mechanisms: convection and diffusion.
Sodium fractions, both the ionized and complexed with non-protein ultrafiltrable anions, follow water during convective transport. Many studies have shown that the ultra-filtrate is hyponatric compared with plasma water undergoing ultrafiltration, ,, and that both total and plasma water ionized sodium concentrations increase during isolated ultrafiltration.  This is probably due to the so-called Donnan effect, which is related to the negatively charged plasma proteins incapable of crossing the dialysis membrane.
In the past, in order to obtain the value of ultrafiltrable sodium during hemodialysis (HD), total plasma sodium concentration was measured by flame photometry. The plasma water sodium concentration was calculated according to the total protein concentration multiplied by 0.95, which accounted for the correcting factor of the Donnan effect. , Currently, it seems to be quite acceptable for clinical purposes to assume that the plasma water sodium concentration directly measured by potentiometry is equivalent to the total ultrafiltrable sodium.
If there is no sodium removal by diffusion, sodium removal can be computed as the ultrafiltrable plasma water sodium concentration multiplied by the total amount of water removed.
The sodium flux across the dialyser by diffusion is a function of the sodium activity in the blood and dialysate streams.  To obtain the diffusible fraction of sodium (i.e. the ratio between the ionized sodium concentrations in the ultrafiltrate and in plasma water 2 ), the inlet plasma water sodium activity measured by direct potentiometry should be corrected for a Donnan factor of 0.967. As the dialysate is protein-free, the ionized sodium concentration directly measured by ionometry can be considered as the concentration available for diffusion. 
When dialysate sodium activity corresponds to plasma water sodium activity multiplied by 0.967 ("isonatric" dialysate) and there is no ultrafiltration, the net intradialytic sodium removal is zero. The use of a "low" sodium dialysate leads to a sodium removal by diffusion that may be useful when the programmed ultrafiltration is insufficient to remove the accumulated amount of sodium. However, we feel that this is not a sound practice because of the risk of cellular overhydration consequent to the osmotic fluid shift from the extracellular to intracellular compartment. The use of a "high" dialysate sodium concentration is more frequently required in order to avoid the excessive sodium losses due to ultrafiltration and to prevent the cardiovascular instability, which is certainly the most important acute hemodialysis-related complication.  However, "hypernatric dialysis" may lead to insufficient sodium removal and favor the development of hypertension, cardiac failure and pulmonary edema.
It has been suggested that intradialytic side effects can be reduced by means of "sodium ramping", a technique based on the use of a variable concentration of sodium in the dialysate, which is generally high at the beginning and low at the end of the dialysis session. The rationale for this therapy is twofold.  First, during ultrafiltration, the patient tends to develop extracellular fluid volume contraction that may be minimized by increasing the sodium concentration, which moves water from the intracellular to the extracellular fluid. Secondly, during dialysis, as solutes (primarily urea) are removed, plasma osmolality falls and thus water moves into cells, potentially causing the disequilibrium syndrome. The use of a higher sodium dialysate concentration at the beginning of dialysis, when the urea removal is the greatest, may reduce symptoms related to the disequilibrium syndrome.
A study by Levin and Goldstein compared the ramped hypertonic sodium dialysis (RHSD) with the standard dialysis (SD) [Table - 1], showing an improvement in the well-being of patients (reduction in cramps, headache, hangover).  However, in our study  in which we chose a fixed dialysate sodium concentration for all of the patients, regardless of their plasma sodium concentrations, interdialytic sodium intakes and programmed ultrafiltration, we obtained very different intradialytic sodium-removal values [Table - 2]. Another study by Lam Sui Sang et al.  compared the standard dialysis, characterised by a constant dialysate sodium concentration, with linear or stepwise sodium ramping [Table - 1]. The results showed a reduction in episodes of hypotension and cramps with sodium ramping (both linear and stepwise). However, there was an associated increase in the sense of thirst, weight gain and elevation of blood pressure. As in the study by Levin and Goldstein, the sodium removal was very different in the three profiles [Table - 2], so in these studies the clinical differences observed may have been simply due to differences in sodium balance and not to differences in sodium profiles. A study by Movilli et al,  considering the decrease in blood volume as the main cause of intradialytic hypotension, compared the effects of the three different profiles of dialysate sodium concentration [Table - 1] on the same blood volume. The results showed a lower intradialytic percent reduction in blood volume (continuously monitored by on-line optical reflection method) with the high-to-low dialysate sodium profile as compared to both low-tohigh profile and constant dialysate sodium concentration. This study, unlike the previous ones, took into account the intradialytic sodium balance [Table - 2], but it was performed using the sodium plasma concentrations measured by flame photometry. One has to remember, however, that using flame photometry would be correct only if the plasma protein concentration remained constant during dialysis, an assumption that is not realistic in clinical practice. Therefore, since these values have not been corrected for protein concentration, one cannot know whether a zero sodium balance has really been achieved in all of these three sodium profiles. Recently, Oliver et al  have compared the standard dialysis with the dialysis characterised by the combination of sodium and ultra-filtration profiling. During the profiled treatments, the initial dialysate sodium concentration of 152 mmol/l was decreased exponentially over the first 150 min to 142 mmol/l and thereafter kept constant [Table - 1]. In the same way, the ultrafiltration rate was automatically decreased exponentially. There was no difference in the post-dialysis weight, but the post-dialysis serum sodium was greater during the profiled treatment compared with the standard treatment [Table - 2]; meaning that less sodium was removed without an increase in the sense of thirst, weight gain or blood pressure.
Sodium ramping may be an adequate approach towards decreasing dialysis symptoms. However, further studies comparing different dialysate sodium profiles, with respect to the sodium balance, are needed to correctly evaluate the impact of this technique on patient tolerance to the dialytic treatment.
It has been reported that, in comparison to hemodialysis, hemofiltration (HF) and hemodiafiltration lead to a lower intradialytic morbidity rate.  Recently, Locatelli et al  have compared the data obtained from eight patients treated with predilution HF with the calculated post-dilution HF and hemodialysis data. The study showed that sodium removal was similar using both HF modalities at the same total dialysate and reinfusate sodium concentrations, and lower than hemodialysis. This study has raised some doubts about the intrinsic ability of HF to improve cardiovascular stability by some mechanisms other than sodium removal.
Sodium kinetic model
In 1980, Gotch et al proposed a kinetic model for determining the individual adequate dialysate sodium concentration needed to achieve a zero balance between intradialytic sodium removal and interdialytic sodium load.  The sodium kinetic model calculates the dialysate sodium concentration needed to achieve the end-dialysis plasma water sodium concentration necessary to obtain a zero sodium balance over the treatment cycle.
It has been shown that this early analytical single-pool kinetic model, which uses flame photometry to determine plasma and dialysate sodium concentrations, has a level of imprecision of ± 2.8 mEq/l in predicting end-dialysis plasma water sodium concentration.  However, on the basis of its theoretical premises, Di Filippo et al have more recently developed a single-pool kinetic model, which calculates the ionized dialysate sodium concentration required to reach a pre-established target of enddialysis blood sodium activity. This model has a level of imprecision of less than 0.84 mEq/l, with laboratory error accounting for 60% of the overall error.  Unfortunately, neither of these models is suitable for routine clinical use because of the need for blood sampling and laboratory determinations at each dialysis session.
Given the linear correlation between the conductivity of each electrolyte solution and its sodium content, the conductivity values can be used instead of sodium concentration values. According to the basic theory developed by Polashegg,  if the dialysate conductivity is measured at the dialyser inlet and outlet ports, at two different inlet conductivity values, the ionic dialysance can be easily calculated. Furthermore, the plasma water conductivity can also be calculated. The sodium kinetic model may therefore be changed into a conductivity kinetic model, which allows predicting the final plasma water conductivity and determining the dialysate conductivity required to obtain a desired final plasma water conductivity. A specially designed "Biofeedback Module" (BM-COT Hospal) is capable of determining the effective ionic dialysance and plasma water conductivity, without the need for blood and dialysate sampling, thus allowing repeated determinations and ensuring that the results are immediately available. ,
Moreover, based on the single-pool conductivity model, this module automatically changes the inlet dialysate conductivity in order to achieve a prescribed end-dialysis plasma water conductivity.
It has been shown that the conductivity kinetic model, using this biofeedback module, has a level of imprecision of less than ± 0.14 mS/cm, roughly equivalent to ± 1.4 mEq/l in terms of ionized plasma water sodium concentration. 
The sodium kinetic model developed for hemodialysis cannot be correctly applied to hemodiafiltration techniques because the higher ultrafiltration rates may interfere with the total inlet dialysate sodium concentration.
Hemodiafiltration forms a special case by its paired filtration dialysis (PFD) in which convection and diffusion take place separately. Considering sodium convective and diffusive removal separately, Di Filippo et al,  developed a single-pool sodium kinetic model that makes it possible to identify the required ionized dialysate sodium concentration (as measured by means of direct potentiometry), or the total reinfusate sodium concentration (as measured by means of flame photometry), that are needed to obtain a pre-established end-dialysis ionized plasma water sodium concentration. The mean difference between the predicted and measured end-PFD plasma water ionized sodium concentrations was 0.00 + 0.55 mEq/l, which means that the model has an imprecision of < 1.1 mEq/l.
Nevertheless, this model requires to determine at least the plasma water sodium concentration at the start of each dialysis session and so it is unsuitable for routine clinical application. The same authors developed a PFD conductivity kinetic model,  which showed an imprecision of < 0.1 mS/cm.
The use of the sodium/conductivity kinetic model would permit to obtain a zero sodium balance. However, does it permit to reduce intradialytic morbidity as well? A multicenter prospective controlled and randomised trial  was carried out to test whether the clinical implementation of this conductivity kinetic model was capable of significantly improving cardiovascular stability. The study compared two treatments (A = conventional PFD, B = PFD using the kinetic model) in two sequences (1 = ABB and 2 = BAA), with a run-in period (A) being followed by three consecutive experimental periods. The study demonstrated that, in comparison with conventional PFD, the application of the conductivity kinetic model improves the cardiovascular stability in hemodialysis patients prone to dialysis hypotension. [Figure - 1] shows a reduction in the number of dialysis sessions characterised by symptomatic or asymptomatic hypotension in the sequence 1; and a reduction in the number of dialysis sessions characterised by symptomatic hypotension with a shift from symptomatic to asymptomatic hypotension in the sequence 2.
| Conclusions|| |
In order to improve cardiovascular stability, the dialysate sodium concentrations have been progressively increased in the last decades. However, although this is effective in reducing the intradialytic morbidity, the systematic use of higher sodium concentrations is not without disadvantages such as hypertension and pulmonary edema.
The studies on "sodium ramping" have demonstrated a decrease in the intradialytic side effects, but generally with a lower sodium removal. Recently, it has been suggested that the improved cardiovascular stability that characterises the convective techniques may depend on lower sodium removal than in hemodialysis, with the same consequent drawbacks.
In clinically stable patients, the amount of sodium removed during dialysis has to be equal to the amount of sodium accumulated during the interdialytic period to ensure a physiological zero balance. Since the interdialytic sodium load varies from one uremic patient to another, its removal should be individualised, which can be done mainly by adjusting the sodium content in the dialysate with respect to the ultrafiltration rate. The sodium kinetic model makes it possible to calculate the dialysate sodium concentration needed to achieve the end-dialysis plasma water sodium concentration necessary to obtain a zero sodium balance over the treatment cycle. However, this model is unsuitable for routine clinical practice, because of the need for blood and dialysate samples.
This drawback could be overcome by using the on-line conductivity kinetic model. The application of the mathematical model in clinical practice seems to improve effectively the intradialytic cardiovascular stability (with respect to the sodium balance), as it was demonstrated in a multicenter prospective controlled and randomised trial, applying the model in PFD. Other studies are necessary to confirm the real clinical advantages of the implementation of the conductivity kinetic model in hemodialysis, which is the most commonly used dialysis technique.
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[Figure - 1]
[Table - 1], [Table - 2]