Acute effects of hemodialysis on nitrite and nitrate: potential cardiovascular implications in dialysis patients

Cardiovascular mortality in dialysis patients remains a serious problem. It is 10 to 20 times higher than in the general population. No molecular mechanism has been proven to explain this increased mortality, although nitric oxide (NO) has been implicated. The objective of our study was to determine the extent of the removal of the NO congeners nitrite and nitrate from plasma and saliva by hemodialysis, as this might disrupt physiological NO bioactivity and help explain the health disparity in dialysis patients. Blood and saliva were collected at baseline from patients on dialysis and blood was collected as it exited the dialysis unit. Blood and saliva were again collected after 4–5h of dialysis. In the 27 patients on dialysis, baseline plasma nitrite and nitrate by HPLC were 0.21±0.03 and 67.25±14.68μM, respectively. Blood immediately upon exit from the dialysis unit had 57% less nitrite (0.09±0.03μM; P=0.0008) and 84% less nitrate (11.04μM; P=0.0003). After 4–5h of dialysis, new steady-state plasma levels of nitrite and nitrate were significantly lower than baseline, 0.09±0.01μM (P=0.0002) and 16.72±2.27μM (P=0.001), respectively. Dialysis also resulted in a significant reduction in salivary nitrite (232.58±75.65 to 25.77±10.88μM; P=0.01) and nitrate (500.36±154.89 to 95.08±24.64μM; P=0.01). Chronic and persistent depletion of plasma and salivary nitrite and nitrate probably reduces NO bioavailability and may explain in part the increased cardiovascular mortality in the dialysis patient. ► We demonstrate the effects of hemodialysis on steady-state nitrite and nitrate levels. ► Disruption of the enterosalivary circulation of nitrate may lead to a loss of NO activity. ► Loss of plasma and salivary nitrite and nitrate may have negative health outcomes. ► This study provides new considerations for anion repletion in dialysis patients.