Our results highlight the importance of a run-in phase using a protocolized blood pressure algorithm when treatment modalities cannot be blinded. The decline in blood pressure at the end of the 3 month run-in phase, compared to baseline, was likely multifactorial. Although we did not demonstrate a reduction in average post dialysis weight, there was tremendous variability with some participant’s weight being decreased and other participant’s weight being increased. Similar changes were seen in the anti-hypertensive medication use. A reduction in dialysate sodium has been associated with a reduction in blood pressure in hypertensive Isoacteoside patients without a change in pre-dialysis serum sodium concentration in somebut not all studies. Post dialysis increases in serum sodium have been demonstrated for patients Danshensu treated with conventional hemodialysis with dialysate sodium that is higher than the patient’s serum sodium with a potential increase in thirst. It is unclear if the dietary instruction or the decrease in dialysate sodium in our study caused the small but statistically significant decrease in the total amount of ultrafiltration from the first month of the run in phase to the last month of the run in phase. The mechanism for the decrease in antihypertensive requirements on short daily hemodialysis, compared to conventional hemodialysis, is unclear. A reduction in ECFV has been demonstrated in somebut not allstudies as a mechanism contributing to the blood pressure lowering effect associated with short daily dialysis. Our study does not support this association for the population. There are a number of potential reasons for the differences in our results compared to other studies. To our knowledge a protocolized blood pressure management algorithm aimed at achieving an optimal dry weight prior to starting short daily hemodialysis has not been followed previously. Even during conventional hemodialysis ‘probing dry weight’ as was done in the DRIP trial was associated with approximately 7/3 mmHg decline in systolic and diastolic blood pressure respectively. Also, given the inability to blind these modality studies, the possibility of differential patient management is possible. The activity of the sympathetic nervous system was found to be important in a study that included 11 patients treated with short daily hemodialysis. The investigators demonstrated a reduction in ultrafiltration volumes per session almost identical to those reported in our study. They hypothesized that large volume fluctuations could result in greater sympathetic nervous system stimulation. Greater amounts of ultrafiltration may also lead to increased post dialysis serum sodium which may stimulate the sympathetic nervous system. We were unable demonstrate a difference in serum catecholamines with short daily compared to conventional hemodialysis but this does not rule out increase central sympathetic outflow. In that last decade there has been an emerging evidence to support importance of oxidative stress in the development of hypertension. Hydrogen peroxide productionwas higher in granulocytes of patients with CKD treated with hemodialysis compared to controls. The magnitude of ROS production by granulocytes and monocytes in that study population was significantly related to the plasma concentration of the lipid peroxidation product, malondialdehyde, which is commonly used as an indirect marker of oxidative stress.