**4.2.2 Sodium measurements and Gibbs-Donnan considerations**

By convention, ionometric serum sodium measurements are corrected to reflect sodium concentration in the total serum volume thereby giving results to historicalresults equivalent to historical flame photometry (Burnett et al., 2000). Given that sodium is distributed only in the water phase, laboratory measures will underestimate the sodium available for dialytic exchange. Actual values should be raised by 7% given usual levels of proteins and lipids. The Gibbs-Donnan effect demonstrates, however, that not all this sodium is available for dialytic exchange. Negatively charged plasma proteins interact with a portion of ionized sodium essentially removing it from the ionic pool. This effect lowers the "plasma diffusible sodium by 4-5%" (Santos, 2008), essentially cancelling out the overestimation of the lab value (Lindley, 2009). More correctly, the accounting for plasma proteins is unnecessary as lab convention and Gibbs-Donnan cancel each other out; however, lipids are uncharged and

and dialysate sodium estimations equivalent concepts? As will be demonstrated below, predialysis serum sodium tends to be relatively constant over time, eliminating the need to measure the sodium every treatment. Further, conventions in laboratory reporting and the Gibbs-Donnan effect influence the direction of diffusive mass transfer between serum and

Pre-dialysis serum sodium remains rather constant over time. The sodium setpoint in dialysis patients is the mean monthly pre-dialysis sodium concentration. In 58 patients over 9 to 16 months, dialyzing against constant dialysate sodium of 143mEq/L, within-subject variability of serum sodium was only 0.62 +/- 0.42 mEq/L (Mean +/- 2 Standard Deviations). Further, the average serum sodium among the 58 patients was 137.3 +/- 2.5 mEq/L (mean +/- SD). Therefore, 98% of this population was dialyzing against relatively hypertonic dialysate even at

Over the short term, the sodium set point remains constant even when dialysate sodium is manipulated. During a brief evaluation, 27 patients maintained constant pre-dialysis serum sodium despite reduction of dialysate sodium to 95% of serum sodium. The average serum sodium was 134.0 +/- 1.4 during the first 3 weeks dialyzing against 138 mEq/L and

During longer studies it appears that the sodium set point can be influenced slightly by changes of dialysate sodium. Over an 18-week period, 11 patients had a small but statistically significant increase in pre-dialysis sodium when the time-averaged concentration (TAC) of Na+ was raised from 140 to 147 mEq/L (138.1+/-0.1 to 138.6+/-0.2) (Song et al., 2002). Similar findings were seen in subgroup analysis of 52 patients over 8 months. Patients in the upper tertile of pre-dialysis serum sodium at study entry had a small but statically significant decrease in pre-dialysis serum sodium from 141 to 140 mEq/L (p=0.003) after the dialysate sodium was dropped from 141 to 138 mEq/L (Thein et al, 2007). Several other studies show that the sodium set point may be somewhat more mutable; however, each significant change seems to be related to sub- or super-physiologic dialysate sodium concentrations (Wilkinson et al., 1977; Fischbach et al., 1988; Acchiardo & Hayden, 1991). When dialyzing across a *physiologic* range of dialysate sodium, however, the concept of a set point remains valid, as variation of predialysis serum sodium is less than 1% (Song

By convention, ionometric serum sodium measurements are corrected to reflect sodium concentration in the total serum volume thereby giving results to historicalresults equivalent to historical flame photometry (Burnett et al., 2000). Given that sodium is distributed only in the water phase, laboratory measures will underestimate the sodium available for dialytic exchange. Actual values should be raised by 7% given usual levels of proteins and lipids. The Gibbs-Donnan effect demonstrates, however, that not all this sodium is available for dialytic exchange. Negatively charged plasma proteins interact with a portion of ionized sodium essentially removing it from the ionic pool. This effect lowers the "plasma diffusible sodium by 4-5%" (Santos, 2008), essentially cancelling out the overestimation of the lab value (Lindley, 2009). More correctly, the accounting for plasma proteins is unnecessary as lab convention and Gibbs-Donnan cancel each other out; however, lipids are uncharged and

the rather 'physiological' sodium of 143meq/L (Keen & Gotch, 2007).

remained 134.0 +/- 1.5 (mean +/- SD) after the decrease (de Paula et al., 2004).

et al., 2002; de Paula et al., 2004; Keen & Gotch, 2007; Thein et al, 2007).

**4.2.2 Sodium measurements and Gibbs-Donnan considerations** 

dialysate.

**4.2.1 Sodium setpoint** 

therefore do not participate in Gibbs-Donnan. Thus diffusible serum sodium is higher than expected in proportion to the lipid content of serum. In patients with relatively normal lipids, however, this difference is small enough to be ignored. In summary, dialysate sodium set to serum sodium can be considered functionally isonatric.
