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

Circulation

Accepted October 22, 2012Received March 6, 2012.

Abstract

Background—The role of statins in the prevention of contrast induced acute kidney injury (CIAKI) is controversial.

Methods and Results—We investigated 1) the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease (CKD) enrolled into the NAPLES II trial were randomly assigned to a) Atorvastatin group (80 mg within 24 hours before contrast media (CM) exposure; n = 202), or b) Control group (n = 208). All patients received high dose of N-acetylcysteine and sodium bicarbonate solution. 2) the in vitro effects of atorvastatin pre-treatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (i.e. an increase >10% of serum cystatin C [sCyC] concentration within 24 hours after CM exposure) occurred in 9/202 patients in the Atorvastatin group (4.5%) and in 37/208 patients in the Control group (18.4%) (p = 0.005; OR = 0.22; 95% CI = 0.07-0.69). CIAKI rate was lower in the Atorvastatin group both in diabetics and non-diabetics and in patients with moderate CKD (estimated glomerular filtration rate [eGFR] 31 to 60 ml/min/1.73 m2). In the in vitro model, pre-treatment with atorvastatin 1) prevents CM-induced renal cell apoptosis by reducing stress kinases activation, and 2) restored the survival signals (mediates by Akt and Erks 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.