Clinical Trial: Effect of Statin Treatment on Urinary AQP2 (uAQP2/01)

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Urinary AQP2 Excretion in Hypercholesterolemic Patients as a Measure of Effect of Statin Therapy

Brief Summary: The purpose of this study is to test the hypothesis that the function and/or regulation of urinary aquaporin 2 in hypercholesterolemic humans is affected by standard statin therapy, as compared with diet alone

Detailed Summary:

Statins are the first-line recommended pharmacological therapy in patients with dyslipidemias and play a key role in both primary and secondary prevention of coronary heart disease. By decreasing plasma total and low-density lipoprotein cholesterol (LDL-C) concentrations, statins decrease the risks for atherosclerotic cardiovascular disease and associated morbidity and mortality. Statins occupy part of the active binding site of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) and inhibit its enzymatic activity in the liver, a key step leading to the reduction of cellular sterol pool. Statins also have beneficial effects on the vascular wall by stabilizing the atherosclerotic plaques, ameliorating impaired endothelial function, and reducing vascular inflammation.

Besides the well-known metabolic and cardiovascular effects, it has been recently shown that statins increase the plasma membrane expression of the renal water channels Aquaporin 2 (AQP2). Water reabsorption in the kidney connecting tubule and collecting duct is regulated by the antidiuretic hormone arginine vasopressin (AVP), which promotes plasma membrane expression of the water channe aquaporin 2 (AQP2), the rate-limiting step controlling reabsorption of water, thus urine concentration, in this segment of the nephron. The investigators reported a number of evidences showing that statins accumulate AQP2 at the apical membrane of collecting duct cells by a AVP-independent mechanism. The effect of statins on AQP2 is independent of classical cholesterol homeostasis but rather depends on depletion of mevalonate-derived intermediates of cholesterol synthetic pathways, i.e. isoprenoid intermediates, including farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP).

Water balance disorders are often associated with defects of AQP2 trafficking. Nephrogenic Dia
Sponsor: University of Bari

Current Primary Outcome: uAQP2 [ Time Frame: 0, 1, 4, 12 weeks ]

Urinary AQP2 excretion during therapy (statin or diet)


Original Primary Outcome: Same as current

Current Secondary Outcome: Cholesterolemia [ Time Frame: 0, 1, 4, 12 weeks ]

Serum cholesterol during therapy (statin or diet)


Original Secondary Outcome: Same as current

Information By: University of Bari

Dates:
Date Received: August 10, 2015
Date Started: October 2013
Date Completion:
Last Updated: August 11, 2015
Last Verified: August 2015