key: cord-0065791-eacjdhj8 authors: Yu, Albert S; Liang, Brannen; Yang, Su-Jau T; Kim, Brendan J; Huang, Cheng-Wei; Sim, John J title: Statin use and survival among ESKD patients hospitalized with sepsis date: 2021-01-11 journal: Clin Kidney J DOI: 10.1093/ckj/sfab001 sha: 36871f3a54f6ca11de70040cc477a579ace3aa3f doc_id: 65791 cord_uid: eacjdhj8 nan Sepsis is a common cause of mortality in hospitalized patients in the USA and worldwide [1] . Among patients with end-stage kidney disease (ESKD), sepsis is the second most common known cause of mortality, trailing only mortality from cardiac causes [2] . Sepsis is presumed to arise from the dysregulation of the immune response to infection [3] . Although standard treatment relies on maintaining tissue perfusion and initiation of empiric antibiotics, statins have been implicated as having a potential mortality benefit in sepsis [4] . Widely known for their lipid-lowering properties, statins are also thought to have inherent anti-inflammatory properties [5] . Although chronic kidney disease is a risk-enhancing factor for atherosclerotic cardiovascular disease, the most recent guidelines provided by the American Heart Association do not recommend the initiation of statins for adults requiring dialysis treatment based on lack of cardiovascular benefit [6] . Supporting this guideline, rosuvastatin was shown not to have a significant benefit in composite cardiovascular death, nonfatal myocardial infarction and stroke in patients receiving hemodialysis [7] . However, to date, studies have not investigated whether statins affect sepsis mortality in the ESKD population. Thus, we sought to determine whether chronic statin use was associated with mortality benefits among ESKD patients hospitalized for sepsis within the Kaiser Permanente Southern California (KPSC) healthcare system. A retrospective cohort study was performed among patients admitted to the hospital with a diagnosis of both sepsis and ESKD [obtained through the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) and ICD-10-CM] between 1 January 2008 and 30 September 2018. The KPSC ESKD population is racially/ethnically diverse and generally reflective of the KPSC membership population [8, 9] . Statin users were defined as those having filled two prescriptions for a statin within 6 months prior to admission, with the second prescription filled within 30 days prior to admission based on the KPSC pharmacy and analytic database. The primary outcome of 30-day allcause mortality was analyzed unweighted and weighted using the Inverse Probability Treatment Weighting (IPTW) method. A total of 8858 patients were included in our study, with 2820 on statins and 6038 not on statins at the time of admission for sepsis. At baseline, there were differences between statin users and non-users in age, sex, race and comorbidities such as heart disease, hypertension, cerebrovascular disease and diabetes (Table 1) . Thus, we used the IPTW method to create synthetic groups to more adequately compare the effect of statin exposure. After IPTW, statin users and non-users were similar across many of the covariates analyzed such as sex, race, heart failure, ischemic heart disease, cerebrovascular disease and renin angiotensin system blocker use. However, significant differences between statin users and non-users remained for Our findings from a real-world population suggest that statin use is associated with lower mortality among ESKD patients hospitalized for sepsis. A strength of our study includes the large, diverse patient population obtained through the comprehensive electronic health records. Potential limitations of our study include the fact that we were not able to fully propensity match certain covariates such as hypertension, diabetes and hyperlipidemia between statin users and non-users, which may confound the interpretation of our findings. In addition, we did not have information on type of dialysis access (fistulas, grafts and catheters) for the entire study population. Nonetheless, our study sheds light on the potential benefits of statins in the ESKD population, a population that is highly prone to infections and infection-related mortality. Although previous studies have not demonstrated a cardiovascular mortality benefit from statin use in ESKD patients, statins have been shown to provide a mortality benefit in a subset of the ESKD population, such as those with acute myocardial infarction [10] . While additional studies are warranted, our findings suggest a potential benefit of statins for ESKD patients hospitalized for sepsis, a population that is highly susceptible to infections. This work was supported and funded by the Kaiser Permanente Regional Research Committee and the KPSC Clinician Investigator Award (to J.J.S.). Sepsis: a roadmap for future research USRDS Annual Data Report: Epidemiology of kidney disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases The immunopathology of sepsis and potential therapeutic targets A population-based cohort study on the drug-specific effect of statins on sepsis outcome Inflammation and cardiovascular disease: from pathogenesis to therapeutic target PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines Rosuvastatin and cardiovascular events in patients undergoing hemodialysis Disparities in early mortality among chronic kidney disease patients who transition to peritoneal dialysis and hemodialysis with and without catheters COVID-19 and survival in maintenance dialysis Statin treatment in dialysis patients after acute myocardial infarction improves overall mortality The authors would like to thank the KPSC Renal Business Group for their support and providing information on the KPSC ESKD population. None of the authors has any conflicts of interest relevant to this manuscript. The results presented in this paper have not been published previously in whole or part, except in abstract format.