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Plasma levels of endothelin-1 and renal function among young and healthy adults

  • Andreas Fischer , Matthias Bossard , Stefanie Aeschbacher , Peter Egli , Carolin Cordewener , Joel Estis , John Todd , Martin Risch , Lorenz Risch and David Conen EMAIL logo
Published/Copyright: February 21, 2017

Abstract

Background:

Endothelin-1 (ET-1), a vasoconstrictive and pro-inflammatory peptide, is associated with several cardiovascular risk factors and outcomes. We aimed to investigate the association of plasma ET-1 levels and renal function among young and healthy adults.

Methods:

Individuals aged 25–41 years were enrolled in a population-based cohort study. Main exclusion criteria were established kidney disease, cardiovascular diseases, diabetes mellitus and a body mass index>35 kg/m2. Fasting venous plasma samples were used to measure creatinine, cystatin C and ET-1. The estimated glomerular filtration rate (eGFR) was calculated using the creatinine based chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Multivariable regression models were constructed to assess interrelationships of plasma ET-1 with parameters of renal function.

Results:

Median age of the 2139 participants was 37 years, 47% males. Median creatinine and eGFR were 67 μmol/L and 112 mL/min/1.73 m2, respectively. Using quartile one as the reference group, the β-coefficients (95% confidence intervals [CIs]) for eGFR were 0.06 (− 1.22 to 1.35),−0.66 (− 1.95 to 0.62) and−1.70 (− 3.01 to−0.39) for quartiles 2–4 (p-for-trend=0.0056), respectively and β-coefficients (95% CIs) for cystatin C were 0.002 (− 0.01 to 0.02), 0.02 (0.003–0.03) and 0.03 (0.01–0.04) for quartiles 2–4 (p-for-trend<0.0001), respectively. Using ET-1 as a continuous variable, the β-coefficient (95% CI) for eGFR per 1-unit increase was−1.82 (− 3.19 to−0.44, p=0.0095) and 0.02 (0.01–0.04, p=0.0003) for cystatin C. Similar results were found between creatinine and ET-1 levels.

Conclusions:

ET-1 levels are strongly associated with parameters of renal function among young and healthy adults, suggesting an important role of ET-1 and endothelial function in the regulation of kidney function.


Corresponding author: Assoc. Prof. Dr. David Conen, MD, MPH, Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, McMaster University, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada, Phone: + 1 905 905 522 (Ext. 1155)
aAndreas Fischer and Matthias Bossard contributed equally to this work and are shared first authors.
  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The Swiss National Science Foundation, the Liechtenstein Government, the Swiss Heart Foundation, the Swiss Society of Hypertension, the University of Basel, the University Hospital Basel, the Hanela Foundation, Schiller AG and Novartis Foundation supported the GAPP study. Endothelin-1 was measured free of charge by Singulex, Inc., Alameda, CA 94502, USA. Samples were provided and tested for endothelin-1 at Singulex in a blinded manner without access to any variables in the study database other than patient identifiers. Matthias Bossard was supported by grants of the University of Basel and Freiwillige Akademische Gesellschaft (FAG) Basel.

  3. Employment or leadership: John Todd and Joel Estis are employees of Singulex, Inc.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-10-12
Accepted: 2017-1-10
Published Online: 2017-2-21
Published in Print: 2017-7-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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