Endothelial dysfunction and chronic kidney disease: treatment options.

Abstract

Endothelial cells detect physical and chemical changes in the blood vessels, and release various factors to counter these changes to maintain homeostasis. Traditional cardiovascular disease risk factors, such as hypertension, dyslipidemia and diabetes, cause endothelial dysfunction characterized by off-balanced vasodilation/vasoconstriction, increased oxidative stress and inflammation, deregulation of thrombosis and fibrinolysis, abnormal smooth muscle cell proliferation, and a deficient repair mechanism. Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular disease and mortality than the general population. Endothelial dysfunction is commonly observed in CKD, likely preceding other cardiovascular complications. Lipid-lowering agents, such as statins, improve endothelial functions and are effective in reducing cardiovascular disease risk in the general population, but have not demonstrated comparable efficacy in the CKD patient population. Similarly, antidiabetic agents, such as thiazolidinediones, that improve endothelial function in the general population are less efficacious than expected in slowing disease progression and reducing cardiovascular disease risk in CKD patients. Interestingly, agents that activate the vitamin D receptor (VDR) for the treatment of hyperparathyroidism secondary to CKD are associated with a survival benefit in CKD patients that is likely mediated through the effects of the VDR on modulating key components involved in endothelial dysfunction. However, a randomized, clinical study is required to confirm the survival benefit of VDR activation therapy for CKD patients. Results from clinical studies suggest that managing hypertension alone may not be adequate in slowing CKD progression and its related cardiovascular complications. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers that target the renin-angiotensin system slow CKD progression, possibly due to their effects on improving endothelial function, independent of controlling blood pressure.

• Authors: J Ruth Wu-Wong
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 9 Issue 9 Pg. 970-82 (Sep 2008) ISSN: 1472-4472 [Print] England
• PMID: 18729004 (Publication Type: Journal Article, Review)

Chemical References

• Hypoglycemic Agents
• Receptors, Calcitriol

Topics

• Animals
• Cardiovascular Diseases (complications, physiopathology)
• Dyslipidemias (blood, physiopathology)
• Endothelium, Vascular (physiopathology)
• Humans
• Hypertension, Renovascular (drug therapy)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Kidney Failure, Chronic (complications, drug therapy, physiopathology)
• Oxidative Stress (drug effects)
• Receptors, Calcitriol (drug effects)
• Vasoconstriction (drug effects, physiology)
• Vasodilation (drug effects, physiology)