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Publications

Journal Article Review Ppublish

PubMed: 40423627 DOI: 10.1152/ajpheart.00908.2024

Endothelial dysfunction in chronic kidney disease: a clinical perspective.

Am J Physiol Heart Circ Physiol 329(1):H135-H153

Authors: Monique E Cho, Vienna E Brunt, Yan-Ting Shiu, Kanokwan Bunsawat

Affiliations

  • Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States.
  • Renal Section, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States.
  • Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
  • Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah, United States.
  • Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States.
  • Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States.
  • Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, United States.

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.

MeSH

Exercise, Kidney Diseases, Mortality, Kidney, Oxidative Stress, Uremia, Morbidity, Endothelium