**5.2 Concentrate formulations**

All the liquid and dry concentrates in the Fresenius NaturaLyte® - 4000 Series of Acid and Bicarbonate will result in a final sodium concentration of 137mEq/L once mixed. Fresenius Citrasate® Series results in a base sodium of 137.3 mEq/L once mixed with the NaturaLyte® Bicarbonate (Fresenius, 2010). Rockwell Medical produces three series of formulations available in dry and liquid. The Rockwell Medical R-Series results in final sodium concentrations of 138, 139, 140, 143 mEq/L. The C-Series results in 137mEq/L. The F-Series results in 135 or 138 mEq/L (Rockwell Medical, 2009). Minntech's Centrisol® results in a final sodium concentration of 137 mEq/L and their Renasol® results in 139,140,142,or 143 mEq/L (Minntech, 2010).


Table 4. The default sodium concentration of several available dialysate concentrates and the sodium contribution from the acid portion (Fresenius, 2010; Minntech, 2010; Rockwell Medical 2009). \*RenalPure® Liquid Acid with SteriLyte® Liquid Bicarbonate or Dri-Sate® Dry Acid with RenalPure® Powder Bicarbonate.

the 'ideal' sodium level as eventually an "Individualized" approach should be introduced. Staff awareness, training and 'buy in' are the only way to deliver individualized sodium.

Modern dialysate contains bicarbonate; it also contains variable amounts of calcium and magnesium. If such a solution were stored for any length of time, calcium and magnesium would combine with bicarbonate and precipitate out of solution. Dialysate must also be at physiologic pH which is, unfortunately, ideal for bacterial growth. In order to avoid these untoward consequences, bicarbonate is kept separate from calcium and magnesium in separate solutions or powders. The nomenclatures for these concentrates are "Acid" and "Bicarbonate". The Acid typically consists of sodium, chloride, potassium, magnesium, calcium, dextrose, acetate, and sometimes citrate. The Bicarbonate concentrate consists of sodium bicarbonate with some brands containing some additional sodium chloride. Creation of dialysate is requires mixing the Acid and Bicarbonate solutions in exact proportions. This is performed in 'real time' in the dialysis machine based on the pre-mixed concentrates of Acid and Bicarbonate and the software programmed for each concentrate.

All the liquid and dry concentrates in the Fresenius NaturaLyte® - 4000 Series of Acid and Bicarbonate will result in a final sodium concentration of 137mEq/L once mixed. Fresenius Citrasate® Series results in a base sodium of 137.3 mEq/L once mixed with the NaturaLyte® Bicarbonate (Fresenius, 2010). Rockwell Medical produces three series of formulations available in dry and liquid. The Rockwell Medical R-Series results in final sodium concentrations of 138, 139, 140, 143 mEq/L. The C-Series results in 137mEq/L. The F-Series results in 135 or 138 mEq/L (Rockwell Medical, 2009). Minntech's Centrisol® results in a final sodium concentration of 137 mEq/L and their Renasol® results in 139,140,142,or 143

**Company/ Product Final Na+ (mEq/L) Na+ from Acid (mEq/L)** 

 NaturaLyte® 137 100 Citrasate® 137.3 100.3

 Centrisol® 137 unlisted Renasol® 139,140,142,143 unlisted

 R-Series\* 138, 139, 140, 143 79, 80, 81, 84 C-Series\* 137 100 F-Series\* 135, 138 100, 103

Table 4. The default sodium concentration of several available dialysate concentrates and the sodium contribution from the acid portion (Fresenius, 2010; Minntech, 2010; Rockwell Medical 2009). \*RenalPure® Liquid Acid with SteriLyte® Liquid Bicarbonate or Dri-Sate®

**5.1 Review of dialysate generation** 

**5.2 Concentrate formulations** 

mEq/L (Minntech, 2010).

Fresenius

Minntech

Rockwell Medical

Dry Acid with RenalPure® Powder Bicarbonate.

### **5.3 Dialysate proportioning systems**

Given that both the Acid and Bicarbonate concentrates contain significant sodium (sodium chloride in Acid and sodium bicarbonate in the Bicarbonate). The sodium can therefore varied by adjusting the dilution of the Acid, Bicarbonate or both. The mechanism of this variation is determined by the design and software of the dialysis machine. Each manufacturer may have slightly different approach. All models of the Fresenius 2008® series (2008H, 2008K, 2008K2, 2008T) have an explicit mechanism behind sodium variation: the amount of Acid concentrate is varied to change the sodium concentration to the target value. The other electrolytes in the Acid component will vary in proportion to the sodium change, while the electrolytes in the Bicarbonate solution will remain unchanged (Fresenius Medical Care, 2001, 2009a, 2009b, 2010). Other manufactures advertise the ability to vary sodium across a wide range. The Gambro Artis® System can vary sodium concentration from 130- 160mEq/L - much wider than the Bicarbonate variability (24-38mEq/L). Therefore the majority, if not all, of the variation in sodium is produced from variation in the Acid concentrate (Gambro, 2008). Similar ranges apply to the Gambro AK96 Advance® and Bio® models: Sodium varies 130-160mEq/L and Bicarbonate 20-40mEq/L (Gambro, 2009). B.Braun's Dialog+® has a conductivity range from 12-17mS/cm, indicating a wide range of sodium variation, however, the relative contribution of Acid and Bicarbonate portions are not readily accessible (B.Braun Medical Inc., 2009). The capability and mechanism of sodium variation for the Baxter TINA® and ARENA® systems are not easily obtainable in an "open access" format. However, given the wide use if sodium modeling over the past two decades, any modern dialysis machine probably has the capability to generate individualized sodium concentrations.

Systems like the Fresenius 2008® Series, which hold the Bicarbonate constant and vary the Acid in order to alter the sodium, will show the greatest variation in the other electrolytes in the acid component. As will be demonstrated below, however, these changes are minute and clinically irrelevant. If any of the other systems utilize a combination of Acid and Bicarbonate variations to alter sodium concentration, the changes in Acid electrolytes will be even less effected (the bicarbonate concentration would vary somewhat, however, the change would also be minimal).

### **5.4 Electrolyte variability during sodium individualization**

The question arises, will there be a change in other electrolyte components during the sodium variation? Clinically these variations are insignificant and should not hinder the use of tailored sodium. Dialysis staff needs to be reassured of this, as many of the newer generation dialysis machines will display the changes to all electrolytes when one is changed. Some staff may see a small change in the potassium and undo the change because the potassium level does not match the prescription. Dialysis unit policy and dialysis orders should be written to accept small variation in other electrolytes during adjustment of sodium. Of note, during sodium profiling, all the acid electrolytes in the same way, resulting in wider, yet still clinically insignificant, fluctuations in the other components.

Here is an example of the nature of electrolyte variation with individualized sodium. A clinician determines that a particular patient's individualized dialysate sodium should be 133mEq/L. Some adjustment of the dialysis machine is required as none of the available base solutions result in this a sodium of 133mEq/L. A Fresenius 2008T®, for example, manipulates the final dialysate sodium by varying concentration of the Acid component

Sodium and Hemodialysis 59

2.00mEq/L of potassium and 100mg/dL of dextrose (Fresenius Medical Care, 2010b). Diluting this Acid by 4% results in Na+ 96mEq/L, K+ 1.92mEq/L, and dextrose 96mg/dL. None of these changes carry a significant clinical effect. The smaller the sodium contribution of the Acid, the other electrolytes will show a larger variation. Table 5 shows the final electrolyte changes of several standard dialysate solutions when using the proportioning

Dialysate sodium concentration must be prescribed for each dialysis session. Dialysate sodium standards vary from 126.5mEq/L to greater than 155mEq/L through out the history of dialysis. While higher concentrations can be used to promote greater hemodynamic stability during dialysis, their cost is worsening hypertension and greater interdialytic weight gain. Glycosaminoglycans and other polyanions sequester sodium out of the osmotic pool and amplify the sodium gain during hypertonic dialysis causing greater effects than the traditional 'sodium space' model would predict. We reviewed 17 prospective and retrospective studies that quantify the effects of dialysate sodium on hypertension, interdialytic weight gain and intradialytic hypotension. In order to minimize undesired effects of high or low sodium for the most patients, "facility-wide" dialysate sodium setting of 137mEq/L should be implemented. An individualized sodium prescription can be calculated by setting dialysate sodium equal the patient's serum sodium. This calculation can be done without adjustments since laboratory conventions and the Gibbs-Donnan effect essentially negate each other. In order to deliver a facility-wide or individualized sodium prescription, changing dialysate concentrates could be undertaken but not necessary: modern proportioning systems can adjust the dilution of dialysate Acid or Bicarbonate components. Usually the dilution of the Acid is adjusted while Bicarbonate remains constant. The other Acid electrolytes will vary by the same percentage as the sodium

system to decrease the base sodium by 5mEq/L.

variation: a clinically inconsequential change.

pp. M135-7. ISSN 0889-7190

No.58, (July 1923), pp.13, ISSN 0036-8075

MG thanks Camelia, Natalie & Kaitlyn. You are the light of my world.

Acchiardo, S. & Hayden, A. (1991). Is Na+ modeling necessary in high flux dialysis?

Adair, G. (1923). On the Donnan Equilibrium and the Equation of Gibbs. *Science*. Vol.6,

Argiles, A., Lorho, R., Servel M., Chong G., Kerr P. & Mourad, G. Seasonal modifications in

*American Society for Artificial Internal Organs Transactions*. Vol. 37, No.3, (July 1991),

blood pressure are mainly related to interdialytic body weight gain in dialysis patients. *Kidney International*. Vol.65, No.5, (May 2004), pp. 1795-1801. ISSN 0085-

**7. Acknowledgments** 

**8. References** 

2538

**6. Conclusions** 

(Fresenius Medical Care, 2010a). If the available dialysate has a base sodium of 137mEq/L and the Acid concentrate contributes 100mEq/L (such as Fresenius NaturaLyte®, Citrasate® or Rockwell Medical C-Series), it is possible to predict the changes on the other electrolytes. Reducing the final sodium from 137 to 133 mEq/L requires reducing the Acid component from 100meq/L to 96mEq/L (a change of 4%). Reducing each Acid component by 4% will give the final concentration of that component. Using a standard Acid solution, such as Fresenius NaturaLyte® Product Number 08-2201-5, contributes 100mEq/L of sodium,


Table 5. Change in electrolyte concentrations resulting from an individualized sodium prescription. This example shows what happens to the other electrolytes after a 5mEq/L reduction in dialysate sodium. The breakdown of the Acid portion of several common concentrates is shown in the center column (Rockwell Medical, 2009; Fresenius Medical Care, 2010b). Based on the percent change of Acid sodium, the resulting values for potassium, calcium, magnesium, chloride, acetate and dextrose are listed in the left column.

(Fresenius Medical Care, 2010a). If the available dialysate has a base sodium of 137mEq/L and the Acid concentrate contributes 100mEq/L (such as Fresenius NaturaLyte®, Citrasate® or Rockwell Medical C-Series), it is possible to predict the changes on the other electrolytes. Reducing the final sodium from 137 to 133 mEq/L requires reducing the Acid component from 100meq/L to 96mEq/L (a change of 4%). Reducing each Acid component by 4% will give the final concentration of that component. Using a standard Acid solution, such as Fresenius NaturaLyte® Product Number 08-2201-5, contributes 100mEq/L of sodium,

**Acid Concentration** 

Na+ (mEq/L) 100 95 (5% reduction)

K+ (mEq/L) 2.0 1.9 Ca++ (mEq/L) 2.00 1.90 Mg++ (mEq/L) 1.00 0.95 Cl-- (mEq/L) 105.0 99.8 Acetate (mEq/L) 4.0 3.5 Dextrose (mg/dL) 100 95

Rockwell Medical, R-205 Na+ (mEq/L) 79 74 (6.33% reduction)

K+ (mEq/L) 3 2.8 Ca++ (mEq/L) 3.5 3.2 Mg++ (mEq/L) 1.5 1.4 Cl-- (mEq/L) 86 80.6 Acetate (mEq/L) 4 3.7 Dextrose (mg/dL) 200 187

Rockwell Medical, F-215 Na+ (mEq/L) 103 98 (4.85% reduction)

K+ (mEq/L) 1 0.95 Ca++ (mEq/L) 2.5 2.37 Mg++ (mEq/L) 1 0.95 Cl-- (mEq/L) 107.5 102.3 Acetate (mEq/L) 3 2.85 Dextrose (mg/dL) 200 190

Table 5. Change in electrolyte concentrations resulting from an individualized sodium prescription. This example shows what happens to the other electrolytes after a 5mEq/L reduction in dialysate sodium. The breakdown of the Acid portion of several common concentrates is shown in the center column (Rockwell Medical, 2009; Fresenius Medical Care, 2010b). Based on the percent change of Acid sodium, the resulting values for

potassium, calcium, magnesium, chloride, acetate and dextrose are listed in the left column.

**New Concentration After 5meq/L Sodium Decrease** 

**Electrolyte Product Number /** 

Fresenius, 08-2201-5

2.00mEq/L of potassium and 100mg/dL of dextrose (Fresenius Medical Care, 2010b). Diluting this Acid by 4% results in Na+ 96mEq/L, K+ 1.92mEq/L, and dextrose 96mg/dL. None of these changes carry a significant clinical effect. The smaller the sodium contribution of the Acid, the other electrolytes will show a larger variation. Table 5 shows the final electrolyte changes of several standard dialysate solutions when using the proportioning system to decrease the base sodium by 5mEq/L.

### **6. Conclusions**

Dialysate sodium concentration must be prescribed for each dialysis session. Dialysate sodium standards vary from 126.5mEq/L to greater than 155mEq/L through out the history of dialysis. While higher concentrations can be used to promote greater hemodynamic stability during dialysis, their cost is worsening hypertension and greater interdialytic weight gain. Glycosaminoglycans and other polyanions sequester sodium out of the osmotic pool and amplify the sodium gain during hypertonic dialysis causing greater effects than the traditional 'sodium space' model would predict. We reviewed 17 prospective and retrospective studies that quantify the effects of dialysate sodium on hypertension, interdialytic weight gain and intradialytic hypotension. In order to minimize undesired effects of high or low sodium for the most patients, "facility-wide" dialysate sodium setting of 137mEq/L should be implemented. An individualized sodium prescription can be calculated by setting dialysate sodium equal the patient's serum sodium. This calculation can be done without adjustments since laboratory conventions and the Gibbs-Donnan effect essentially negate each other. In order to deliver a facility-wide or individualized sodium prescription, changing dialysate concentrates could be undertaken but not necessary: modern proportioning systems can adjust the dilution of dialysate Acid or Bicarbonate components. Usually the dilution of the Acid is adjusted while Bicarbonate remains constant. The other Acid electrolytes will vary by the same percentage as the sodium variation: a clinically inconsequential change.
