Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury

Cristina Quintavalle, Danilo Fiore, Francesca De Micco, Gabriella Visconti, Amelia Focaccio, Bruno Golia, Bruno Ricciardelli, Elvira Donnarumma, Antonio Bianco, Maria Assunta Zabatta, Giancarlo Troncone, Antonio Colombo, Carlo Briguori, Gerolama Condorelli

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND-: The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial. METHODS AND RESULTS-: First, we investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg within 24 hours before contrast media [CM] exposure; n=202) or (2) the control group (n=208). All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution. Second, we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase >10% of serum cystatin C concentration within 24 hours after CM exposure) occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208 patients in the control group (17.8%) (P=0.005; odds ratio=0.22; 95% confidence interval, 0.07-0.69). CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease (estimated glomerular filtration rate, 31-60 mL/min per 1.73 m). In the in vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and (2) restored the survival signals (mediated by Akt and ERK pathways). CONCLUSIONS-: A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI. This beneficial effect is observed only in patients at low to medium risk.

Original languageEnglish
Pages (from-to)3008-3016
Number of pages9
JournalCirculation
Volume126
Issue number25
DOIs
Publication statusPublished - Dec 18 2012

Keywords

  • apoptosis
  • contrast media
  • kidney
  • prevention
  • statins

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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