Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

Endothelial factors in the pathogenesis and treatment of chronic kidney disease Part I: General mechanisms a joint consensus statement from the European Society of Hypertension Working Group on Endothelin and Endothelial Factors and The Japanese Society of Hypertension

Rossi, Gian, Paoloa; Seccia, Teresa, M.a; Barton, Matthiasb; Danser, A.H., Janc; de Leeuw, Peter, W.d,e; Dhaun, Neerajf; Rizzoni, Damianog,h; Rossignol, Patricki; Ruilope, Luis-Miguelj,k,l; van den Meiracker, Anton, H.c; Ito, Sadayoshim; Hasebe, Naoyukin; Webb, David, J.f

doi: 10.1097/HJH.0000000000001599

Kidney damage is a common consequence of arterial hypertension, but is also a cause of atherogenesis. Dysfunction and/or harm of the endothelium in glomeruli and tubular interstitium damage the function of these structures and translates into dynamic changes of filtration fraction, with progressive reduction in glomerular filtration rate, expansion of extracellular fluid volume, abnormal ion balance, and hypoxia, ultimately leading to chronic kidney disease. Considering the key role played by endothelial dysfunction in chronic kidney disease, the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension and the Japanese Society of Hypertension have critically reviewed available knowledge on the mechanisms underlying endothelial cell injury. This resulted into two articles: in the first, we herein examine the mechanisms by which endothelial factors induce vascular remodeling and the role of different players, including endothelin-1, the renin–angiotensin–aldosterone system and their interactions, and of oxidative stress; in the second, we discuss the role of endothelial dysfunction in the major disease conditions that affect the kidney.

aDepartment of Medicine – DIMED, University of Padova, Padova, Italy

bMolecular Internal Medicine, University of Zürich, Zürich, Switzerland

cDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Rotterdam, Rotterdam

dDepartment of Medicine, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Maastricht

eDepartment of Medicine, Zuyderland Medical Center, Geleen-Heerlen, The Netherlands

fUniversity/British Heart Foundation Centre of Research Excellence, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK

gDepartment of Clinical and Experimental Sciences, University of Brescia

hDivision of Medicine, Istituto Clinico Città di Brescia, Brescia, Italy

iInserm, Centre d’Investigations Cliniques-Plurithématique 14–33, Inserm U1116, CHRU Nancy, Université de Lorraine, Association Lorraine de Traitement de l’Insuffisance Rénale, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France

jHypertension Unit, Hospital 12 de Octubre

kDepartment of Postdoctoral Medicine and Investigation, Universidad de Europa

lDepartment of Public Health and Preventive Medicine, Universidad Autonomy, Madrid, Spain

mDivision of Nephrology, Endocrinology and Hypertension, Tohoku University Graduate School of Medicine, Sendai

nDivision of Cardiology, Nephrology, Pulmonology and Neurology, Asahikawa Medical University, Asahikawa, Japan

Correspondence to Gian Paolo Rossi, Clinica dell’Ipertensione Arteriosa, Department of Medicine-DIMED, University Hospital, Via Giustiniani, 2, 35128 Padova, Italy. Tel: +39 049 821 7821; e-mail:

Abbreviations: ACE, angiotensin I-converting enzyme; ADMA, asymmetric dimethylarginine; Ang II, angiotensin II; ARB, angiotensin AT1 receptor blocker; BP, blood pressure; CKD, chronic kidney disease; ECE, endothelin converting enzyme; EDH, endothelium-derived hyperpolarization; eGFR, estimated glomerular filtration rate; EMT, epithelial to mesenchymal transition; ENaC, epithelial or endothelial Na+ channel; eNOS, endothelial nitric oxide synthase; ERA, endothelin receptor antagonist; ESRD, end-stage renal disease; ET-1, endothelin-1; GFR, glomerular filtration rate; GPER, G-protein-coupled estrogen receptor; HIF-1, hypoxia-inducible factor-1; iNOS, inflammatory nitric oxide synthase, NOS 2; L-NMMA, N(G) monomethyl-L-arginine; NO, nitric oxide; NOS, nitric oxide synthase; PIP3, phosphatidyl-inositol (3,4,5) trisphosphate; RAAS, renin–angiotensin–aldosterone system; ROS, reactive oxygen species; VSMC, vascular smooth muscle cells

Received 11 July, 2017

Revised 6 September, 2017

Accepted 20 September, 2017

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.