Abstract

Abstract Background and Aims Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor that plays an important role in the regulation of arterial blood pressure (BP). Elevated levels of plasma ET-1 have been reported in patients with end-stage renal disease (compared with controls), patients on dialysis (compared with non-dialyzed uremic patients), and patients on haemodialysis (compared with peritoneal dialysis). It has been suggested that ET-1 plays a role in BP response to HD; however, the temporal association of changes in ET-1 with changes in BP during the course of an HD session has not been well defined. Moreover, conflicting results have been reported as to the patterns of intradialytic ET-1 changes, with different studies reporting either a decrease, an increase, or no change in ET-1 during HD. The aim of this study was to investigate temporal changes in ET-1 in patients with different intradialytic BP profiles. Methods Data was obtained from a prospective cohort study of 50 maintenance, thrice-weekly HD patients admitted to Brigham and Women's Hospital in Boston, MA, USA. BP was measured before, after, and every 15 min during dialysis using a calibrated ambulatory BP cuff. Blood samples were drawn before dialysis, at 30, 60, and 120 min into HD, and at the end of treatment. Following the exclusion of cases with missing data, shorter dialysis sessions, or very low pre-dialysis BP (below 85/55 mmHg), 42 patients were included in the analysis (17 females, median age 62 years, over 90% diagnosed with hypertension). One HD session was studied in each patient (median ultrafiltration 2.05 L, median duration 232 min). The patients were divided into three subgroups with different patterns of intradialytic systolic blood pressure (SBP): 1) patients with intradialytic hypotension (IDH) defined as: a) drop of SBP to or below 90 mmHg; or b) drop in SBP by at least 30 mmHg associated with at least two hypotension-related symptoms; or c) drop in SBP associated with multiple symptoms requiring intervention; 2) normotensive patients (NT) defined as patients in whom SBP remained between 90 and 130 mmHg for most of the HD session; 3) hypertensive patients (HT) defined as patients in whom the median intradialytic SBP was above 140 mmHg. Results 9 hypertensive patients (HT), 24 IDH patients, and 9 normotensive patients (NT) were identified. In the IDH group, at the end of HD, the median drop in SBP from the pre-HD level was 28 mmHg [25th–75th percentile 10–45 mmHg]. In HT and NT patients, SBP did not change significantly during HD. IDH patients had lower baseline ET-1 (2.2 pg/mL) compared with HT patients (3.4 pg/mL, P = 0.006) but similar compared with NT patients (2.3 pg/mL). ET-1 decreased over the course of dialysis in HT patients (P = 0.02) and NT patients (P = 0.008), whereas no change was observed in IDH patients (P = 0.30). At the end of HD, IDH patients had a similar ET-1 level (2.4 pg/mL) compared with HT patients (2.6 pg/mL) but higher compared with NT patients (1.4 pg/mL, P = 0.004). A moderate negative correlation was found between the dialysis-associated changes in ET-1 and SBP (r = –0.43, P = 0.005) as well as between the baseline ET-1 and baseline SBP in IDH patients (r = –0.42, P = 0.04). Conclusions HD patients may present various patterns of ET-1 changes during HD, which seem to be associated with BP response to HD. In particular, the patterns of ET-1 response to HD may vary among patients categorized as ‘hypertensive’ (the vast majority of patients in our study), who previously were observed to have an intradialytic increase in ET-1. Our results provide a possible explanation as to why previous studies that did not consider intradialytic BP patterns have yielded conflicting results regarding the direction of ET-1 changes during HD.

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