title: Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury.
abstract: BACKGROUND
  The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial.
  
  
  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(2)). 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.
authors.affiliation: Department of Cellular and Molecular Biology and Pathology, and IEOS, CNR, Federico II University of Naples, Via Pansini, 5, I-80121, Naples, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Quintavalle
authors.forename: Danilo
authors.initials: D
authors.lastname: Fiore
authors.forename: Francesca
authors.initials: F
authors.lastname: De Micco
authors.forename: Gabriella
authors.initials: G
authors.lastname: Visconti
authors.forename: Amelia
authors.initials: A
authors.lastname: Focaccio
authors.forename: Bruno
authors.initials: B
authors.lastname: Golia
authors.forename: Bruno
authors.initials: B
authors.lastname: Ricciardelli
authors.forename: Elvira
authors.initials: E
authors.lastname: Donnarumma
authors.forename: Antonio
authors.initials: A
authors.lastname: Bianco
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Zabatta
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
authors.forename: Antonio
authors.initials: A
authors.lastname: Colombo
authors.forename: Carlo
authors.initials: C
authors.lastname: Briguori
authors.forename: Gerolama
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000368:Aged; D000818:Animals; D000069059:Atorvastatin; D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D003287:Contrast Media; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D016159:Tumor Suppressor Protein p53; D000069059:Atorvastatin; D048031:JNK Mitogen-Activated Protein Kinases; D000111:Acetylcysteine