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HDL metabolism and activity in chronic kidney disease

Nosratola D Vaziri1, Mohamad Navab, Alan M Fogelman

  • 1Division of Nephrology and Hypertension, School of Medicine, The City Drive, City Tower, Suite 400, Orange, CA 92868-3217, USA. ndvaziri@uci.edu

Nature Reviews. Nephrology
|March 24, 2010
PubMed

Insights

Chronic kidney disease (CKD) accelerates atherosclerosis due to inflammation and oxidative stress. This review explores how CKD impairs high-density lipoprotein (HDL), worsening cardiovascular risks.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Lipid Metabolism

Background:

  • Chronic kidney disease (CKD) is a significant risk factor for atherosclerosis and cardiovascular mortality.
  • Key contributors to CKD-associated atherosclerosis include inflammation, oxidative stress, and dyslipidemia.
  • Patients with advanced CKD exhibit altered lipoprotein metabolism, including impaired clearance and increased oxidation of apolipoprotein-B, and reduced high-density lipoprotein (HDL) function.

Purpose of the Study:

  • To review the mechanisms underlying high-density lipoprotein (HDL) deficiency and dysfunction in chronic kidney disease (CKD).
  • To examine the consequences of CKD-induced HDL alterations on the development of atherosclerosis and cardiovascular disease.

Main Methods:

  • Review of existing literature on CKD, atherosclerosis, and lipid metabolism.
  • Analysis of findings from animal models of CKD regarding lipid accumulation and kidney injury.
  • Examination of the impact of CKD on cellular lipid metabolism and HDL properties.

Main Results:

  • CKD promotes lipid accumulation in the artery wall and kidneys, contributing to atherosclerosis and kidney damage.
  • Mechanisms include increased cellular lipid uptake, altered fatty acid metabolism, and impaired HDL functions (antioxidant, anti-inflammatory, reverse lipid transport).
  • Current therapies are largely ineffective in addressing CKD-related oxidative stress, inflammation, and HDL dysfunction.

Conclusions:

  • CKD-induced HDL deficiency and dysfunction are critical drivers of atherosclerosis and cardiovascular disease in affected patients.
  • Understanding these mechanisms is essential for developing targeted therapies.
  • There is a pressing need for novel therapeutic strategies to mitigate cardiovascular risk in CKD.

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