Frank Holden Mose

Effect of atorvastatin on renal NO availability and tubular function in patients with stage II-III chronic kidney disease and type 2 diabetes

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BACKGROUND: Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol.

PURPOSE AND METHODS: In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide.

RESULTS: During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged.

CONCLUSION: During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.

Original languageEnglish
JournalScandinavian journal of clinical and laboratory investigation
Volume74
Issue1
Pages (from-to)8-19
Number of pages12
ISSN0036-5513
DOIs
Publication statusPublished - Jan 2014

    Research areas

  • Aged, Arginine Vasopressin, Atrial Natriuretic Factor, Blood Pressure, Cross-Over Studies, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glomerular Filtration Rate, Heart Rate, Heptanoic Acids, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Kidney Tubules, Male, Middle Aged, Natriuretic Peptide, Brain, Nitric Oxide, Pulse Wave Analysis, Pyrroles, Renal Insufficiency, Chronic, Treatment Outcome, Vascular Stiffness, Vasopressins, omega-N-Methylarginine

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