Peri-surgical Statins Lessen Acute Kidney Injury

Abstract

Hepatic hydroxymethyl glutaryl-CoA reductase inhibitors, known as statins, are among the most commonly prescribed drugs in the world. Scientists studying microorganism host defense first identified statins in the 1970s. They were eventually shown in large randomized trials, such as the Scandinavian Simvastatin Survival Study and the West of Scotland Coronary Prevention Study, to confer substantial clinical benefits over placebo in individuals with hypercholesterolemia. Statins are now a cornerstone for both primary and secondary prevention of coronary heart disease. A number of noncardiovascular benefits-such as in dementia, sepsis, and cancer-have also been proposed, largely on the basis of observational data.In this issue of JASN, Molnar et al. 1 report the results of an observational study on the association between statin use and decreased incidence of perioperative acute kidney injury (AKI) and mortality. The population-based cohort contained data on 213,347 Ontario Drug Benefits Plan recipients who were aged Ն66 years and underwent elective cardiac, thoracic, vascular, abdominal, or retroperitoneal surgery between 1995 and 2008. As anticipated, those who received statins tended to have more comorbid atherosclerotic disease, hypertension, diabetes, and congestive heart failure; to be treated with a greater number of total and cardiovascular-related medications; to have undergone more extensive cardiovascular diagnostic evaluations and procedures; and more likely to be undergoing cardiac and vascular surgery. On this basis, unadjusted analyses demonstrated an increased risk in perioperative AKI and dialysis use among statin users. However, upon multivariable and propensity score adjustment, statin use was associated with a 14 to 17% reduction in these outcomes. Curiously, unadjusted mortality was 27% lower in the statin group despite greater comorbid disease burden; mortality risk remained 15 to 21% lower after statistical adjustment. Analyses that appropriately accounted for healthier adherer bias and dose-response trends yielded corroborative findings. The population-based cohort design promotes generalizability, although, in fairness, only to elderly patients undergoing elective surgery.As with all research on humans, internal validity of findings is contingent on accurate characterization of events and conditions. Absent available laboratory data, AKI was characterized solely on the basis of diagnostic codes. Considering the cohort's era, the majority of hospitalizations would have been coded using the International Classification of Diseases, Ninth Revision classification system, which has only 28.3% sensitivity for AKI. 2 Moreover, chronic kidney disease (CKD)-arguably the most important covariate-was assessed with only 22.9% sensitivity and 87.5% specificity (Appendix D-2). 1 Thus, both the outcome and a critical covariate had substantial error rates.An often-repeated mantra in epidemiologic research is that nondifferential misclassification biases toward the null hypothesis. In other words, if inform...

Preoperative Statin Use and Postoperative Acute Kidney Injury

“…Unclear operating characteristics of acute kidney injury diagnostic codes may have promoted misclassification bias and prevented consideration of acute kidney injury severity in gradations short of renal replacement therapy requirement. 18 Other studies have attempted to examine the association between statins and postoperative acute kidney injury among cardiac surgery patients, but were limited by heterogeneity in outcome definitions and relatively small sample sizes. 19–24 …”

Vascular Surgery Kidney Injury Predictive Score: A Historical Cohort Study

“…[25][26][27][28][29] Perhaps this could be due to differences in AKI risk profiles among patients who undergo vascular surgery procedures or the specific drug or dose delivered. Additionally, our study was likely underpowered to detect these differences.…”