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Endothelial dysfunction in chronic kidney disease: a clinical perspective
Journal article   Peer reviewed

Endothelial dysfunction in chronic kidney disease: a clinical perspective

Monique E Cho, Vienna E Brunt, Yan-Ting Shiu and Kanokwan Bunsawat
American journal of physiology. Heart and circulatory physiology, Vol.329(1), pp.H135-H153
07/01/2025
DOI: 10.1152/ajpheart.00908.2024
PMCID: PMC12180289
PMID: 40423627

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Abstract

Chronic kidney disease (CKD) is a progressive, multisystemic disorder that augments the risks of cardiovascular (CV) morbidity and mortality as kidney function declines. The endothelium plays a key role in modulating vascular tone, integrity, and homeostasis by producing and releasing a variety of endothelium-derived relaxing factors, including nitric oxide (NO). Endothelial dysfunction is a salient pathogenic mechanism underlying the development and progression of CKD and is characterized by reduced production of vasodilators and increased production of vasoconstrictors (e.g., endothelin-1). Factors such as the uremic milieu, inflammation, and oxidative stress are putative contributors of endothelial dysfunction and reduced NO bioavailability that ultimately impact functional and structural integrity of the vasculature. Because endothelial dysfunction is an independent predictor of CV morbidity and mortality in patients with CKD, several clinical studies have examined disease-related changes in endothelium-dependent vasodilation across the arterial tree. This review will focus on the clinical evidence regarding CKD-associated endothelial dysfunction involving both the micro- and macrovasculature, briefly discussing underlying physiological mechanisms, and summarizing available and emerging pharmacotherapies along with a brief summary of exercise training as a lifestyle intervention.
 Animals Cardiovascular Diseases - etiology Cardiovascular Diseases - metabolism Cardiovascular Diseases - physiopathology Cardiovascular Diseases - prevention & control Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endothelium, Vascular - physiopathology Humans Nitric Oxide - metabolism Renal Insufficiency, Chronic - complications Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - physiopathology Renal Insufficiency, Chronic - therapy Vasodilation

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