Aspirin reduces the mortality risk of sepsis-associated acute kidney injury: an observational study using the MIMIC IV database

Introduction: Sepsis-associated acute kidney injury (SA-AKI) is a complication of sepsis and is characterized by high mortality. Aspirin affects cyclooxygenases which play a significant role in inflammation, hemostasis, and immunological regulation. Sepsis is an uncontrolled inflammatory and procoagulant response to a pathogen, but aspirin can inhibit platelet function to attenuate the inflammatory response, thus improving outcomes. Several studies have generated contradictory evidence regarding the effect of aspirin on patients with sepsis-associated acute kidney injury (SA-AKI). We conducted an analysis of the MIMIC IV database to investigate the correlation between aspirin utilization and the outcomes of patients with SA-AKI, as well as to determine the most effective dosage for aspirin therapy. Materials and methods: SA-AKI patients’ clinical data were extracted from MIMIC-IV2.1. Propensity score matching was applied to balance the baseline characteristics between the aspirin group and the non-user group. Subsequently, the relationship between aspirin and patient death was analyzed by Kaplan-Meier method and Cox proportional hazard regression models. Results: 12,091 patients with SA-AKI were extracted from the MIMIC IV database. In the propensity score-matched sample of 7,694 individuals, lower 90-day mortality risks were observed in the aspirin group compared to the non-users group (adjusted HR: 0.722; 95%CI: 0.666, 0.783) by multivariable cox proportional hazards analysis. In addition, the Kaplan-Meier survival curves indicated a superior 90-day survival rate for aspirin users compared to non-users (the log-rank test p-value was 0.001). And the median survival time of patients receiving aspirin treatment was significantly longer than those not receiving (46.47 days vs. 24.26 days). In the aspirin group, the average ICU stay length was shorter than non-users group. (5.19 days vs. 5.58 days, p = 0.006). There was no significant association between aspirin and an increased risk of gastrointestinal hemorrhage (p = 0.144). Conclusion: Aspirin might reduce the average ICU stay duration and the 30-day or 90-day mortality risks of SA-AKI patients. No statistically significant difference in the risk of gastrointestinal hemorrhage was found between the aspirin group and the control group.

[1]  D. Cox Sepsis – it is all about the platelets , 2023, Frontiers in Immunology.

[2]  R. Bresalier,et al.  An Aspirin a Day: New Pharmacological Developments and Cancer Chemoprevention. , 2022, Annual review of pharmacology and toxicology.

[3]  Yumei Wang,et al.  Sepsis-induced AKI: From pathogenesis to therapeutic approaches , 2022, Frontiers in Pharmacology.

[4]  R. Touyz,et al.  Differential effects of cyclo-oxygenase 1 and 2 inhibition on angiogenesis inhibitor-induced hypertension and kidney damage , 2022, Clinical science.

[5]  S. Kushimoto,et al.  Antiplatelet pretreatment and mortality in patients with severe sepsis: A secondary analysis from a multicenter, prospective survey of severe sepsis in Japan. , 2022, Journal of critical care.

[6]  Fernando Almeida-Souza,et al.  ATRvD1 Attenuates Renal Tubulointerstitial Injury Induced by Albumin Overload in Sepsis-Surviving Mice , 2021, International journal of molecular sciences.

[7]  S. Massberg,et al.  Interplay between inflammation and thrombosis in cardiovascular pathology , 2021, Nature Reviews Cardiology.

[8]  R. Ajjan,et al.  Antiplatelet therapies in diabetes , 2020, Diabetic medicine : a journal of the British Diabetic Association.

[9]  J. Kellum,et al.  Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. , 2019, Kidney international.

[10]  J. Versmissen,et al.  Aspirin for the prevention and treatment of pre‐eclampsia: A matter of COX‐1 and/or COX‐2 inhibition? , 2019, Basic & clinical pharmacology & toxicology.

[11]  C. Patrono,et al.  Role of aspirin in primary prevention of cardiovascular disease , 2019, Nature Reviews Cardiology.

[12]  Xiaochun Ma,et al.  Effects of antiplatelet therapy on the mortality rate of patients with sepsis: A meta‐analysis , 2019, Journal of critical care.

[13]  R. de Caterina,et al.  The first 3500 years of aspirin history from its roots - A concise summary. , 2019, Vascular pharmacology.

[14]  S. Florquin,et al.  The role of platelets in acute kidney injury , 2018, Nature Reviews Nephrology.

[15]  Xiaochun Ma,et al.  Platelet activation and antiplatelet therapy in sepsis: A narrative review. , 2018, Thrombosis research.

[16]  E. Hawk,et al.  Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention , 2017, Cancer and Metastasis Reviews.

[17]  Sun-Kyung Park,et al.  Preoperative aspirin use and acute kidney injury after cardiac surgery: A propensity-score matched observational study , 2017, PloS one.

[18]  J. Kellum,et al.  Sepsis-induced acute kidney injury , 2016, Current opinion in critical care.

[19]  Ling Zhang,et al.  Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis , 2016, Chinese medical journal.

[20]  Christopher W Seymour,et al.  Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). , 2016, JAMA.

[21]  T. Rea,et al.  Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). , 2016, JAMA.

[22]  Yin Cao,et al.  Aspirin and colorectal cancer: the promise of precision chemoprevention , 2016, Nature Reviews Cancer.

[23]  Y. Arabi,et al.  Association between aspirin therapy and the outcome in critically ill patients: a nested cohort study , 2016, BMC Pharmacology and Toxicology.

[24]  Adil Rafiq Rather,et al.  The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) , 2015 .

[25]  S. Kuo,et al.  Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study , 2015, Intensive Care Medicine.

[26]  S. Shetty,et al.  Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury. , 2014, Toxicology and applied pharmacology.

[27]  D. Alexopoulos,et al.  Use of antiplatelet agents in sepsis: a glimpse into the future. , 2014, Thrombosis research.

[28]  J. Winning,et al.  Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients , 2013, Critical Care.

[29]  B. Engelmann,et al.  Thrombosis as an intravascular effector of innate immunity , 2012, Nature Reviews Immunology.

[30]  A. Khwaja KDIGO Clinical Practice Guidelines for Acute Kidney Injury , 2012, Nephron Clinical Practice.

[31]  E. McBryde,et al.  Acetyl salicylic acid usage and mortality in critically ill patients with the systemic inflammatory response syndrome and sepsis , 2012, Critical care medicine.

[32]  R. de Caterina,et al.  Antiplatelet agents for the treatment and prevention of atherothrombosis. , 2011, European heart journal.

[33]  C. Ronco,et al.  The implications and management of septic acute kidney injury , 2011, Nature Reviews Nephrology.

[34]  J. Freedman,et al.  Platelets and the immune continuum , 2011, Nature Reviews Immunology.

[35]  R. Conroy,et al.  The role of weight and enteric coating on aspirin response in cardiovascular patients , 2010, Journal of thrombosis and haemostasis : JTH.

[36]  J. Lafrance,et al.  Selective and non‐selective non‐steroidal anti‐inflammatory drugs and the risk of acute kidney injury , 2009, Pharmacoepidemiology and drug safety.

[37]  A. Maree,et al.  Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease. , 2005, Journal of the American College of Cardiology.

[38]  C. Serhan,et al.  Resolvins , 2002, The Journal of experimental medicine.

[39]  C. Thiemermann,et al.  Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[40]  P. Halushka,et al.  Protective effects of aspirin in endotoxic shock. , 1981, The Journal of pharmacology and experimental therapeutics.

[41]  L. Hinshaw,et al.  Effects of acetylsalicylic acid on the canine response to endotoxin. , 1967, The Journal of pharmacology and experimental therapeutics.

[42]  G. Macdonald,et al.  Analgesic Nephropathy In Fischer 344 Rats: Comparative Effects Of Chronic Treatment With Either Aspirin Or Paracetamol , 1991, Pathology.

[43]  A. Maree,et al.  E-publications@rcsi Citation Attribution-non-commercial-sharealike 1.0 Volunteers Effect of Enteric Coating on Antiplatelet Activity of Low-dose Aspirin in Healthy Effect of Enteric Coating on Antiplatelet Activity of Low-dose Aspirin in Healthy Volunteers , 2022 .