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Open Access 01-12-2016 | Research article

Association between autonomic nervous dysfunction and cellular inflammation in end-stage renal disease

Authors: Eric Seibert, Kristina Zohles, Christof Ulrich, Alexander Kluttig, Sebastian Nuding, Jan A. Kors, Cees A. Swenne, Karl Werdan, Roman Fiedler, Matthias Girndt

Published in: BMC Cardiovascular Disorders | Issue 1/2016

Abstract

Background

Alterations in autonomic nervous function are common in hemodialysis (HD) patients. Sympathetic as well as parasympathetic activation may be associated with immune and inflammatory responses. We intended to confirm a role of autonomous dysregulation for inflammation in HD patients.

Methods

30 HD patients (including 15 diabetics) and 15 healthy controls were studied for heart rate variability (HRV) using 5 min ECG recordings. Heart rate variability was estimated by time-domain parameters (the standard deviation of the RR intervals (SDNN) and the percentage of pairs of adjacent RR intervals differing by >50 ms (pNN50)) and frequency-domain-analysis (high- and low-frequency variation of RR intervals, HF and LF). Inflammation was detected as serum C-reactive Protein (CRP), IL-6 and circulating monocyte subpopulation numbers. Immune cells were characterized by ACh receptor expression.

Results

Patients differed from controls in terms of age (68.0 [14.8] yrs vs. 58.0 [13.0] yrs, p < 0.001; Median [IQR]) and sex. However, HRV parameters were different in controls and HD patients (SDNN controls 34.0 [14.0] ms, HD patients 15.5 [14.8] ms, p < 0.01). This finding was not restricted to patients with diabetes mellitus (diab), although diabetes is an important cause of autonomous dysfunction (SDNN, diab 13.0 [14.0] ms, non-diab 18.0 [15.3] ms, p = 0.8). LF and HF were reduced by the same magnitude to 1/3 of those in controls. Patients suffered from chronic inflammation (CRP 9.4 [12.9] mg/l, controls 1.6 [2.4] mg/l, p < 0.001) and expanded proinflammatory monocyte subpopulations (CD14++/CD16+ cells: patients 41 [27]/μl, controls 24 [18]/μl, p < 0.01). ECG parameters did not correlate with inflammation in patients, but monocyte ACh receptor expression was enhanced, indicating potentially elevated responsiveness of this cell type to parasympathetic regulation.

Conclusions

HD patients have strongly impaired HRV. Chronic inflammation is not related to autonomous dysfunction, although monocytes express the ACh receptor at enhanced density making them potentially more sensitive to parasympathetic effects.

Trial registration

This study was listed with ClinicalTrials.gov (NCT00878033).

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Title: Association between autonomic nervous dysfunction and cellular inflammation in end-stage renal disease
Authors: Eric Seibert
Kristina Zohles
Christof Ulrich
Alexander Kluttig
Sebastian Nuding
Jan A. Kors
Cees A. Swenne
Karl Werdan
Roman Fiedler
Matthias Girndt
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cardiovascular Disorders / Issue 1/2016
Electronic ISSN: 1471-2261
DOI: https://doi.org/10.1186/s12872-016-0385-1

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