Programmed variable sodium in the dialysate can improve hypotension during hemodialysis but may also alter sodium balance and thus resulting in a increase of water intake and weight gain between dialysis sessions. The aim of this study was to evaluate the changes on plasma volume (PV), Ionic Mass Transfer (IMT) and plasma conductivity (PC) with two different hemodialysis techniques. We studied 10 patients during a four-period protocol (one week each: PF1-DC1-DC2PF2): 120 dialysis sessions. During periods PF1 and PF2, the dialysis procedure was as usual, with exponential decrease of dialysate conductivity (DC) profile (15.7 mS/cm at start, 14.4 mS/cm at middle and 13.8 mS/cm at the end of the session) and UF profile (1.7 1/h at start and 0.1 1/h at the end). During periods DC1 and DC2, DC was automatically determined by a biofeedback modulae (Diacontrol) in order to reach a plasma water conductivity fixed at 14 mS/cm. All hemodialysis parameters were the same for the four periods: duration, blood and dialysate flow rates, dialysis membrane. A lower reduction of PV was evident on PF1 and PF2 (104 +/- 3.26% and -4.36 +/- 2.7%) compared with DC 1 and DC2 (-6.53 +/- 3.31% and -6.67 +/- 3.12%) (p < 0.001). No significant differences were seen in systolic, mean and diastolic blood pressure pre-HD or post-HD, UF, and weight gain, between the four periods. Hypotensive episodes were seen in 33.3% of PF1, 20% of DC1, 23.3% of DC2 and 26.6% of PF2 sessions (NS). PF1 and PF2 periods resulted in a significantly higher 30', mid and post-dialysis PC as compared to DC1 and DC2 periods (p < 0.001). The mean difference between the actual value and the prescribed value of PC at the end of the session was -0.01 +/- 0.07 mS/cm (n: 60). There was a negative correlation between the mean DC during session and the PC at 30' of session. IMT was 420.73 +/- 126.9 mEq in PF1, 311.96 +/- 161.75 in DC1, 278.34 +/- 153.14 in DC2 and 417.66 +/- 152.17 in PF2 (p > 0.001 PF1 and PF2 vs. DC1 and DC2). Diacontrol determines automatically an individualized DC profile for each patient, and accurately reaches the prescribed PC target. By reaching both the dry weight and PC settings, the water and sodium pool is maintained lower in the hemodialysis session using a biofeedback module. Clinical tolerance was similar in the two different dialysis procedures.