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Impact of a High Loading Dose of Atorvastatin on Contrast-Induced Acute Kidney Injury
Study Questions:
Does high dose atorvastatin prevent contrast-induced nephropathy?
Methods:
The authors assessed the impact of atorvastatin on renal function among patients with chronic kidney disease who were enrolled in the NAPLES II (Novel Approaches for Preventing or Limiting Events II) trial. Patients were randomly assigned to either the atorvastatin group (80 mg within 24 hours before contrast exposure [n = 202] or the control group [n = 208]). All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution. Further, they investigated the in vitro effects of atorvastatin pretreatment on contrast media-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. Contrast-induced acute kidney injury (CIAKI) was defined as an increase >10% of serum cystatin C concentration within 24 hours after contrast media exposure.
Results:
CIAKI 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, but no benefit was observed in those with severe renal dysfunction (estimated glomerular filtration rate <30 ml/min per 1.73 m2). There was a trend toward reduction in contrast-induced nephropathy, defined as an increase of serum creatinine concentration of ≥0.5 mg/dl at 48 hours (3.5% in the atorvastatin group vs. 7.7% in the control group, p = 0.085). In the in vitro model, pretreatment with atorvastatin prevented contrast media-induced renal cell apoptosis by reducing stress kinases activation and restored the survival signals (mediated by Akt and ERK pathways).
Conclusions:
A single high loading dose of atorvastatin administered within 24 hours of contrast exposure is associated with a reduction in CIAKI.
Perspective:
Contrast-induced nephropathy is associated with a high morbidity, mortality, and health care cost. This study demonstrates a benefit of high-dose statin loading in reducing CIAKI, although the clinical implications of this remain unknown. High-dose statin loading is a safe strategy and needs to be explored further for its renoprotective properties.
Keywords: Pyrroles, Apoptosis, Coronary Angiography, Acute Kidney Injury, Heptanoic Acids, MAP Kinase Signaling System, Diabetes Mellitus, Renal Insufficiency, Chronic, Cystatin C
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