Effects of statins on renal sodium and water handling: acute and short-term effects of atorvastatin on renal haemodynamics, tubular function, vasoactive hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans

Nephrol Dial Transplant. 2008 May;23(5):1556-61. doi: 10.1093/ndt/gfm807. Epub 2007 Dec 8.

Abstract

Background: Statins have a beneficial effect on cardiovascular morbidity and mortality due to a reduction in plasma cholesterol. However, statins seem to have effects beyond the lowering of plasma cholesterol. We hypothesize that these effects are caused by an effect on renal function.

Methods: We measured the effects of atorvastatin (AS) on renal function in two randomized, placebo-controlled, double-blinded and crossover studies in healthy man. In an acute trial (Study 1), 19 subjects received either 80 mg AS as a single dose or placebo. In a short-term trial (Study 2), 20 subjects received either 80 mg AS or placebo daily for 4 weeks. In both studies glomerular filtration rate (GFR), renal plasma flow (RPF), plasma concentrations of angiotensin II (Ang II), renin (PRC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), aldosterone (Aldo), vasopressin (AVP) and blood pressure (BP) were determined.

Results: In Study 1 AS decreased fractional excretion of sodium (FE(Na)) significantly (P = 0.035), but very modestly, and reduced diastolic BP (P = 0.024). Apart from this, we found no significant differences in GFR, RPF, tubular function and vasoactive hormones in either Study 1 or 2.

Conclusions: An acute dose of AS decreased FE(Na) and DBP in healthy humans. The reduction in fractional urinary sodium excretion was very modest and transitory, and most likely secondary to the fall in diastolic blood pressure (DBP). However, renal haemodynamics, tubular function, vasoactive hormones and blood pressure were unchanged during short-term statin treatment in healthy man.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin II / blood
  • Arginine Vasopressin / blood
  • Atorvastatin
  • Atrial Natriuretic Factor / blood
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Diuresis / drug effects
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects
  • Heart Rate / drug effects
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Kidney / drug effects*
  • Kidney / physiology*
  • Kidney Tubules / drug effects
  • Kidney Tubules / physiology
  • Male
  • Natriuresis / drug effects
  • Natriuretic Peptide, Brain / blood
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology*
  • Renal Plasma Flow / drug effects

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Angiotensin II
  • Arginine Vasopressin
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor
  • Atorvastatin