**4.2.1 Sodium setpoint**

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

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

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