Impact of a High Loading Dose of Atorvastatin on Contrast-Induced Acute Kidney Injury
Open Access
- 18 December 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 126 (25), 3008-3016
- https://doi.org/10.1161/circulationaha.112.103317
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 m2). 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.This publication has 40 references indexed in Scilit:
- Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II)Circulation, 2011
- Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular AngiographyCirculation, 2011
- In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosisCell Death & Disease, 2011
- Statins inhibit the growth of variant human embryonic stem cells and cancer cells in vitro but not normal human embryonic stem cellsBritish Journal of Pharmacology, 2009
- Contrast-Induced Nephropathy and Long-Term Adverse EventsClinical Journal of the American Society of Nephrology, 2009
- JNK signaling in apoptosisOncogene, 2008
- Asialoerythropoietin Prevents Contrast-Induced NephropathyJournal of the American Society of Nephrology, 2008
- Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injuryCritical Care, 2007
- Statins as antioxidant therapy for preventing cardiac myocyte hypertrophyJCI Insight, 2001
- Tolerance and Pharmacokinetics of Single‐Dose Atorvastatin, a Potent Inhibitor of HMG‐CoA Reductase, in Healthy SubjectsThe Journal of Clinical Pharmacology, 1996