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High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

ABSTRACT: Statins affect several mechanisms underlying acute kidney injury (AKI).To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery.Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center.Patients naive to statin treatment (n?=?199) were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery (n?=?102) or matching placebo (n?=?97). Patients already taking a statin prior to study enrollment (n?=?416) continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after (n?=?206) or matching placebo (n?=?210), and resumed taking the previously prescribed statin on postoperative day 2.Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery (Acute Kidney Injury Network criteria).The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) receiving atorvastatin. The board later recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] were women; 202 [32.8%] had diabetes) completed the study. Among all participants (n?=?615), AKI occurred in 64 of 308 (20.8%) in the atorvastatin group vs 60 of 307 (19.5%) in the placebo group (relative risk [RR], 1.06 [95% CI, 0.78 to 1.46]; P?=?.75). Among patients naive to statin treatment (n?=?199), AKI occurred in 22 of 102 (21.6%) in the atorvastatin group vs 13 of 97 (13.4%) in the placebo group (RR, 1.61 [0.86 to 3.01]; P?=?.15) and serum creatinine concentration increased by a median of 0.11 mg/dL (10th-90th percentile, -0.11 to 0.56 mg/dL) in the atorvastatin group vs by a median of 0.05 mg/dL (10th-90th percentile, -0.12 to 0.33 mg/dL) in the placebo group (mean difference, 0.08 mg/dL [95% CI, 0.01 to 0.15 mg/dL]; P?=?.007). Among patients already taking a statin (n?=?416), AKI occurred in 42 of 206 (20.4%) in the atorvastatin group vs 47 of 210 (22.4%) in the placebo group (RR, 0.91 [0.63 to 1.32]; P?=?.63).Among patients undergoing cardiac surgery, high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall, among patients naive to treatment with statins, or in patients already taking a statin. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery.clinicaltrials.gov Identifier: NCT00791648.

SUBMITTER: Billings FT

PROVIDER: S-EPMC4843765 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Billings Frederic T FT Hendricks Patricia A PA Schildcrout Jonathan S JS Shi Yaping Y Petracek Michael R MR Byrne John G JG Brown Nancy J NJ

JAMA 20160301 9

<h4>Importance</h4>Statins affect several mechanisms underlying acute kidney injury (AKI).<h4>Objective</h4>To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery.<h4>Design, setting, and participants</h4>Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center.<h4>Interventions</h4>Patients naive to statin tre ...[more]

PMID: 26906014

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Project description:BackgroundCardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality. We examined the utility of combining biomarkers of kidney function loss (serum cystatin C) and kidney tubular damage (urine neutrophil gelatinase-associated lipocalin [NGAL] and Kidney Injury Molecule-1 [KIM-1]) for the prediction of post-cardiac surgery AKI.MethodsSingle-center prospective cohort study of 106 adults undergoing coronary artery bypass grafting and/or valve surgery with cardiopulmonary bypass (CPB). Primary outcome was postoperative in-hospital AKI defined by serum creatinine (SCr)-Kidney Disease: Improving Global Outcomes criteria. Biomarkers were measured preoperatively, 6 hours after CPB and on postoperative days (PODs) 1 to 4.ResultsA total of 23 subjects (21.7%) developed AKI. After adjusting for preoperative left ventricular ejection fraction, body mass index >30 kg/m2, and estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2, the combination of peak serum cystatin C and peak urine KIM-1/creatinine (Cr) (6 hours post-CPB to POD 1) above optimal cutoff significantly associated with postoperative AKI (odds ratio [OR]: 5.32; 95% confidence interval [CI]: 1.31-21.67; P = 0.020). This biomarker combination significantly improved the performance of the clinical model for the prediction of postoperative AKI (area under the curve [AUC]: 0.77, 95% CI: 0.65-0.90 for the clinical model alone versus 0.83, 95% CI: 0.73-0.93 for the clinical model with the addition of biomarker data, P = 0.049).ConclusionsCombining biomarkers of postoperative kidney function loss and postoperative kidney tubular damage significantly improved prediction of in-hospital AKI following cardiac surgery. Future large, multicenter studies are warranted to assess whether panels of biomarkers reflecting distinct pathobiology can be used to guide interventions and improve short- and long-term outcomes in patients undergoing cardiac surgery.

Project description:BackgroundAcute kidney injury (AKI) is a relevant complication after cardiac surgery and is associated with significant morbidity and mortality. Existing risk prediction tools have certain limitations and perform poorly in the Chinese population. We aimed to develop prediction models for AKI after valvular cardiac surgery in the Chinese population.MethodsModels were developed from a retrospective cohort of patients undergoing valve surgery from December 2013 to November 2018. Three models were developed to predict all-stage, or moderate to severe AKI, as diagnosed according to Kidney Disease: Improving Global Outcomes (KDIGO) based on patient characteristics and perioperative variables. Models were developed based on lasso logistics regression (LLR), random forest (RF), and extreme gradient boosting (XGboost). The accuracy was compared among three models and against the previously published reference AKICS score.ResultsA total of 3,392 patients (mean [SD] age, 50.1 [11.3] years; 1787 [52.7%] male) were identified during the study period. The development of AKI was recorded in 50.5% of patients undergoing valve surgery. In the internal validation testing set, the LLR model marginally improved discrimination (C statistic, 0.7; 95% CI, 0.66-0.73) compared with two machine learning models, RF (C statistic, 0.69; 95% CI, 0.65-0.72) and XGBoost (C statistic, 0.66; 95% CI, 0.63-0.70). A better calibration was also found in the LLR, with a greater net benefit, especially for the higher probabilities as indicated in the decision curve analysis. All three newly developed models outperformed the reference AKICS score.ConclusionAmong the Chinese population undergoing CPB-assisted valvular cardiac surgery, prediction models based on perioperative variables were developed. The LLR model demonstrated the best predictive performance was selected for predicting all-stage AKI after surgery.Clinical trial registrationTrial registration: Clinicaltrials.gov, NCT04237636.

Project description:BackgroundPreliminary evidence suggests a nephroprotective effect of urinary alkalinization in patients at risk of acute kidney injury. In this study, we tested whether prophylactic bicarbonate-based infusion reduces the incidence of acute kidney injury and tubular damage in patients undergoing open heart surgery.Methods and findingsIn a multicenter, double-blinded (patients, clinical and research personnel), randomized controlled trial we enrolled 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass. At induction of anesthesia, patients received either 24 hours of intravenous infusion of sodium bicarbonate (5.1 mmol/kg) or sodium chloride (5.1 mmol/kg). The primary endpoint was the proportion of patients developing acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL), initiation of acute renal replacement therapy, and mortality. The study was stopped early under recommendation of the Data Safety and Monitoring Committee because interim analysis suggested likely lack of efficacy and possible harm. Groups were non-significantly different at baseline except that a greater proportion of patients in the sodium bicarbonate group (66/174 [38%]) presented with preoperative chronic kidney disease compared to control (44/176 [25%]; p?=?0.009). Sodium bicarbonate increased urinary pH (from 6.0 to 7.5, p<0.001). More patients receiving bicarbonate (83/174 [47.7%]) developed acute kidney injury compared with control patients (64/176 [36.4%], odds ratio [OR] 1.60 [95% CI 1.04-2.45]; unadjusted p?=?0.032). After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90-2.33], p?=?0.120]). A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p?=?0.011). The incidence of postoperative renal replacement therapy was similar but hospital mortality was increased in patients receiving sodium bicarbonate compared with control (11/174 [6.3%] versus 3/176 [1.7%], OR 3.89 [1.07-14.2], p?=?0.031).ConclusionsUrinary alkalinization using sodium bicarbonate infusion was not found to reduce the incidence of acute kidney injury or attenuate tubular damage following open heart surgery; however, it was associated with a possible increase in mortality. On the basis of these findings we do not recommend the prophylactic use of sodium bicarbonate infusion to reduce the risk of acute kidney injury. Discontinuation of growing implementation of this therapy in this setting seems to be justified.Trial registrationClinicalTrials.gov NCT00672334 Please see later in the article for the Editors' Summary.

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High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

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High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

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