|dc.description.abstract||Hypertension is present in approximately 86% of patients with end-stage kidney disease (ESKD) receiving maintenance hemodialysis. (1) It is a key risk and mechanistic factor in the development of cardiovascular disease, which is the leading cause of mortality in this population. (2) Extremes of high or low blood pressures (BP) during HD treatment are frequently encountered in clinical practice and are associated with poor outcomes, including mortality. (1, 3) While in most patients, systolic BP (SBP) tends to decrease during dialysis, approximately 13-23% of patients experience intradialytic hypertension, characterized by an increase in SBP from pre-HD to post-HD. (4- 6) Previous evidence has suggested an association between intradialytic hypertension and adverse outcomes; (4, 6, 14-19) however, there is no consistent, unifying definition for intradialytic hypertension described in the literature. This has hindered a robust assessment of risks and potential predictors of this phenomenon, as well as limiting comparisons across prior studies. To address this gap, in Paper 1 we explored three potential definitions of intradialytic hypertension and evaluated their independent associations with mortality in a large contemporary US-based patient cohort.
The clinical management of intradialytic hypertension is complex and predicting which patients will experience a paradoxical increase in BP, versus other patterns of change in BP during HD, remains a challenge. (6-8) One of the keys to solving this issue is to gain a better understanding of the underlying pathophysiology. Although many potential etiologies have been invoked and studied (including volume overload, the use of erythropoiesis-stimulating agents (ESAs), and endothelial cell dysfunction), Endothelin-1 (ET-1) has emerged as a key potential mediator. ET-1 is a potent endothelium-derived vasoconstrictor, which has previously been associated with essential hypertension in the non-HD population and adverse outcomes in patients receiving hemodialysis. (20) A study by Teng et al. reported that inappropriate rises in ET-1 were associated with increased peripheral resistance and resultant increases in SBP. (21) These results were further corroborated by Chou et al. in a case-control study which observed significant increases in post-HD ET-1 in participants who were “hypertension-prone” as compared to “non-hypertension prone” HD controls. (22) However, as these studies were relatively small (≤60 patients) and of limited duration, a knowledge gap remains to robustly examine the association of ET-1 with pre- SBP parameters in the maintenance HD population. In Paper 2, harnessing the wealth of repeated measures analysis and intradialytic BP recordings, we assessed the association of baseline ET-1 in outpatient HD patients with changes in SBP parameters (pre-SBP, intra-HD SBP, and post-SBP) over one year in large, contemporary, US-based cohort.
In summary the significance of this work is that as the HD population is at high risk for cardiovascular mortality and since there have been very few advances that have modified this risk, identifying novel opportunities for intervention that may modify this risk will be of great benefit.||