Acute Effect of High vs Low Dialysate Sodium on Endothelial Cell Function During Hemodialysis
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BACKGROUND: Intradialytic hypertension (HTN), a rise in blood pressure that occurs during hemodialysis (HD) treatments in up to 15% of patients, is associated with higher morbidity and mortality. The cause of intradialytic HTN is unknown but may be due to endothelial cell (EC) dysfunction. In vitro exposure of ECs to high sodium (Na+) concentration promotes EC stiffness and imbalances in vasoconstrictors (endothelin-1 [ET-1]) and vasodilators (nitric oxide [NO]). We hypothesized that, among patients with intradialytic HTN, exposure to high dialysate Na+ would lead to a decrease in NO and increase in ET-1 during HD. METHODS: We performed a 3-week, 2-arm, randomized crossover study among 16 HD patients with intradialytic HTN and compared the effects of high dialysate-to-serum Na+ gradients (5 mEq/L above participants' baseline Na+) vs low dialysate-to-serum Na+ gradients (5 mEq/L below baseline Na+ with lower limit of 134 mEq/L) on intradialytic changes in nitrite and ET-1. Differences between treatments were compared with repeated measures mixed linear regression and included randomization arm (high - low Na+ vs low - high Na+), treatment effect (high vs low Na+), subject, time and session. RESULTS: Study participants (N=16) had an average age of 58.8 years, 38% were black, 56% were Hispanic, and 94% were male. Intradialytic changes in NO and ET-1 with high and low dialysate-to-plasma Na+ gradients are shown in Figure 1. In the primary comparison of high vs low dialysate-to-serum Na+ gradient, there were no significant differences in intradialytic levels of NO or ET-1 (Table 1). However, when compared by randomization arm, participants who received the low dialysate-to-serum Na+ gradient followed by high compared to those who received the high dialysate-to-serum Na+ gradient followed by low had a significant decrease in ET-1 (parameter estimate -0.49 pg/mL, p=0.04) and significant increase in nitrite during hemodialysis (parameter estimate +0.16 nM, p=0.02) (Table 1). CONCLUSIONS: Patients who received the low dialysate-to-serum Na+ gradient before the high dialysate-to-serum Na+ gradient had higher levels of nitrite and lower levels of ET-1 throughout the three week study period compared to patients who received the high dialysate-to-serum Na+ gradient before the low dialysate-to-serum Na+ gradient. This suggests that the dialysate Na+ concentration may have longer-term effects on endothelial cell function.