Introduction

End-stage renal disease (ESRD) patients with a paradoxical increase in blood pressure (BP) during hemodialysis (HD), termed intradialytic hypertension (ID-HTN), are at significantly increased risk for mortality and adverse cardiovascular events. ID-HTN affects up to 15% of all HD patients, and the pathophysiologic mechanisms remain unknown. We hypothesized that ESRD patients prone to ID-HTN have heightened volume-sensitive cardiopulmonary baroreflex sensitivity (BRS) that leads to exaggerated increases in sympathetic nervous system (SNS) activation during HD.

Methods

We studied ESRD patients on maintenance HD with ID-HTN (n = 10) and without ID-HTN (controls, n = 12) on an interdialytic day, 24 to 30 hours after their last HD session. We measured continuous muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, and electrocardiography (ECG) at baseline, and during graded lower body negative pressure (LBNP). Low-dose LBNP isolates cardiopulmonary BRS, whereas higher doses allow assessment of physiologic responses to orthostatic stress.

Results

The ID-HTN patients had significantly higher pre- and post-HD BP, and greater interdialytic fluid weight gain compared to controls. There was a significantly greater increase in MSNA burst incidence (P = 0.044) during graded LBNP in the ID-HTN group, suggesting heightened cardiopulmonary BRS. The ID-HTN group also had a trend toward increased diastolic BP response during LBNP, and had significantly greater increases in BP during the cold pressor test.

Conclusion

Patients with ID-HTN have augmented cardiopulmonary BRS that may contribute to increased SNS activation and BP response during HD.

Psychosocial stress can affect cardiovascular health through multiple pathways. Certain stressors, such as socioeconomic disadvantage, childhood adversity, intimate partner violence, and caregiving stress, are especially common among women. The consequences of stress begin at a young age and persist throughout the life course. This is especially true for women, among whom the burden of negative psychosocial experiences tends to be larger in young age and midlife. Menarche, pregnancy, and menopause can further exacerbate stress in vulnerable women. Not only is psychosocial adversity prevalent in women, but it could have more pronounced consequences for cardiovascular risk among women than among men. These differential effects could reside in sex differences in responses to stress, combined with womens propensity toward vasomotor reactivity, microvascular dysfunction, and inflammation. The bulk of evidence suggests that targeting stress could be an important strategy for cardiovascular risk reduction in women.