Association Between Preoperative Statin Use and Acute Kidney Injury Biomarkers in Cardiac Surgical Procedures

Abstract

Background Acute kidney injury is a serious complication of cardiac surgery for which there remains no specific therapy. Animal data and several observational studies suggest that statins prevent acute kidney injury, but the results are not conclusive, and many studies are retrospective in nature. Methods We conducted a multi-center prospective cohort study of 625 adult patients undergoing elective cardiac surgery. All patients were on statins and were grouped on whether statins were continued or held in the 24 hours prior to surgery. The primary outcome was acute kidney injury defined by a doubling of serum creatinine or dialysis. The secondary outcome was the peak level of several kidney injury biomarkers. Results were adjusted for demographic and clinical factors. Results Continuing (vs. holding) a statin prior to surgery was not associated with a lower risk of acute kidney injury defined by a doubling of serum creatinine or dialysis, [adjusted relative risk (RR) 1.09 (95% confidence interval (CI) 0.44, 2.70)]. However, continuing a statin was associated with a lower risk of elevation of the following AKI biomarkers: urine interleukin-18, urine neutrophil gelatinase-associated lipocalin, urine kidney injury molecule-1, and plasma neutrophil gelatinase-associated lipocalin [adjusted RR 0.34 (95% CI 0.18, 0.62), adjusted RR 0.41 (95% CI 0.22, 0.76), adjusted RR 0.37 (95% CI 0.20, 0.76), adjusted RR 0.62 (95% CI 0.39, 0.98), respectively]. Conclusions Statins may prevent kidney injury after cardiac surgery as evidenced by lower levels of kidney injury biomarkers.

Statins and acute kidney injury following cardiac surgery: has the last word been told?

“…On the other hand, patients chronically taking statins should not withdraw the therapy due to its well-established "cardiovascular" benefits (23). In addition, the absence of kidney benefits demonstrated by Billings et al's trial is in line with many large observational studies (17)(18)(19)(20) and a recent Cochrane meta-analysis (14) that do not suggest preoperative statin for kidney protection in adults after surgery under CPB. In order to better understand the potential role of statins and many other drugs and strategies, in CSA-AKI, it could be useful to increase the sensitivity of the investigations moving back from the acute kidney "injury" (a late clinical condition) to the acute kidney "stress" (AKS).…”

“…Due to the potential properties of attenuation of inflammation and oxidative stress (15,16), statins have been administered as kidney protective agents for many years (17). Currently, experimental or retrospective studies have reached inconclusive and sometimes conflicting results (17)(18)(19)(20). In a recent number of JAMA, Billings et al published an interesting double blind randomized controlled trial entitled "High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery", designed to test short-term high-dose perioperative atorvastatin, in both naive and previously treated patients, as a protective drug against CSA-AKI (21 On the contrary, no significant differences in renal function were observed in those patients with CKD who were already taking a statin (P=0.59).…”

“…In light of this, a number of renal biomarkers have been evaluated and tested to enhance the understanding and diagnosis of AKI and cardiorenal syndrome (24,25). Molnar et al conducted a post-cardiac surgery multi-center prospective cohort study of 625 adult patients (18). The primary study's outcome was the need of acute dialysis or a doubling in serum creatinine from the baseline; the secondary outcome was "kidney injury" as identified by elevation of kidney injury biomarkers [urine interleukin-18 (IL-18), urine neutrophil gelatinase-associated lipocalin (uNGAL), urine kidney injury molecule-1 (uKIM-1), and plasma neutrophil gelatinase-associated lipocalin, (uNGAL)].…”

Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials

“…[37][38][39] We and others have shown dissociation between measures of function (serum creatinine) and kidney injury (urinary biomarkers). 34,40 In addition, instead of one peak value of creatinine serving as the input for the AKI-related end point, use of measures of kidney function that better summate the overall burden of acute decline in function, such as the duration of rise in serum creatinine, 41,42 or continuous metrics, such as the average change in creatinine relative to baseline, 43 may improve the ability to detect efficacy or harm signals from the agents.…”

Preoperative Statin Therapy and Renal Outcomes After Cardiac Surgery: A Meta-analysis and Meta-regression of 59,771 Patients

“…46,47 Evidence-based studies to investigate the beneficial role of PST in reduction of postoperative AKI are also sparse. Available reports on the association between PST and the incidence of AKI after cardiac surgery show conflicting results.…”