Dynamics of Cardiac Autonomic Responses During Hemodialysis Measured by Heart Rate Variability and Skin Sympathetic Nerve Activity: The Impact of Interdialytic Weight Gain

Abstract

Background: Autonomic nervous regulation plays a critical role in end-stage kidney disease (ESKD) patients with cardiovascular complications. However, studies on autonomic regulation in ESKD patients are limited to heart rate variability (HRV) analysis. Skin sympathetic nerve activity (SKNA), which noninvasively reflects the sympathetic nerve activity, has not been used in ESKD patients. Methods: Seventy-six patients on maintenance hemodialysis (MHD) treatment (a 4-h HD session, three times a week) were enrolled. Utilizing a noninvasive, single-lead, high-frequency recording system, we analyzed the dynamic change in HRV parameters and SKNA during HD. The different characteristics between the subgroups divided based on interdialytic weight gain (IDWG, <3 kg or ≥3 kg) were also demonstrated. Results: After the HD, values for heart rate (75.1 ± 11.3 to 80.3 ± 12.3 bpm, p < 0.001) and LF/HF (1.92 ± 1.67 to 2.18 ± 2.17, p = 0.013) were significantly higher than baseline. In subgroup analysis, average voltage of skin sympathetic nerve activity (aSKNA) in IDWG ≥3 kg group was lower than the IDWG <3 kg group at the end of MHD (1.06 ± 0.30 vs 1.32 ± 0.61 μV, p = 0.046). Moreover, there was a linear correlation between mean heart rate (HR) and aSKNA in low IDWG patients (p < 0.001), which was not found in high IDWG patients. At the 1-year follow-up, high IDWG patients had a higher incidence of cardiovascular hospitalization (p = 0.046). Conclusions: In MHD patients, a gradual activation of sympathetic nerve activity could be measured by HRV and aSKNA. A lower aSKNA at the end of HD and a loss of HR-aSKNA correlation in overhydrated patients were observed. Extensive volume control is promising to improve the autonomic nervous function and clinical outcomes in this population.

Keywords: autonomic nervous system; end-stage kidney disease; heart rate variability; hemodialysis; interdialytic weight gain (IDWG); skin sympathetic nerve activity.

FIGURE 1

Graphical illustration of this study. (A) 76 ESKD patients receiving MHD therapy were included in this study. IDWG refers to the fluid accumulated between two times of HD as illustrated. (B) Home-made wearable devices were applied to record high-frequency signals for further analysis. Following previous protocols, electrode patches were placed in the left subclavicular area, right subclavicular area, and right abdomen. (C,D) Representative workflow of data processing. Raw data was applied to a 500–1000 Hz bandpass filter to get SKNA (C) and 0.5–150 Hz bandpass filter to get ECG (D). R-wave peaks were extracted for further HRV analysis using the PhysioNet toolbox.

FIGURE 2

The overall trend of physiological measurements during 4-h hemodialysis. Systolic blood pressure, diastolic blood pressure, mean heart rate, average skin sympathetic nerve activity, and representative HRV indices (SDNN, LF/HF, SD1/SD2, SampEn) were demonstrated. “*” stands for statistically significant (p < 0.05) by one-way repeated measures ANOVA adjusted by Bonferroni’s multiple comparisons test (vs the baseline). Error bars stand for the standard error of the mean (SEM).

FIGURE 3

HR-aSKNA correlation between Group A (IDWG≥3 kg) and Group B (<3 kg). (A,B) Subgroup analysis showed aSKNA (A) and the difference of aSKNA to the baseline in 0–30 min (△aSKNA) (B). The aSKNA in 210–240 min was significantly higher in Group B (IDWG <3 kg). “*” stands for statistically significant (p < 0.05) by Student’s t test between two subgroups. (C,D) The relationship of HR and aSKNA in Group A (C) or Group B (D) was demonstrated in eight periods (0–30, 30–60, 60–90, 90–120, 120–150, 150–180, 180–210, 210–240 min). (E,F) There was no HR-aSKNA correlation observed in patients in Group A (E, p = 0.688). Instead, a linear correlation was found in Group B (F, p < 0.001).

FIGURE 4

HRV indices between Group A (IDWG≥3 kg) and Group B (IDWG<3 kg). Representative time domain (SDNN, RMSSD, |AC|, DC), frequency domain (TP, LF, HF, LF/HF), and nonlinear (SD1, SD2, SD1/SD2, SampEn) measurement of HRV between subgroups. Red and blue lines stand for Group A (IDWG≥3 kg) and Group B (IDWG<3 kg), respectively. “*” stands for statistically significant (p < 0.05) by Student’s t test between two subgroups. Error bars stand for the standard error of the mean (SEM).

FIGURE 5

HRV dynamic changes in Group A (IDWG≥3 kg) and Group B (IDWG<3 kg). Changes in the time domain (SDNN, RMSSD, |AC|, DC), frequency domain (TP, LF, HF, LF/HF), and nonlinear (SD1, SD2, SD1/SD2, SampEn) measurement of HRV compared with 0–30 min in two subgroups. Red and blue lines or “*” stand for IDWG≥3 kg and IDWG<3 kg, respectively. “△” stands for the difference compared to the baseline. “*” stands for statistically significant (p < 0.05) by one-way repeated measures ANOVA adjusted by Bonferroni’s multiple comparisons tests (vs the baseline in 0–30 min). Error bars stand for the standard error of the mean (SEM).