Effect of ondansetron on reducing ICU mortality in patients with acute kidney injury

Xiaojiang Guo,Lirong Wang,Yu Chen,Andrew D La,Richard Bertz,John A Kellum,Zeyu Liu,Michael Gilbert,Xiguang Qi,Peihao Fan

doi:10.1038/s41598-021-98734-x

Xiaojiang Guo, Lirong Wang + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-98734-x

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Abstract

The purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients’ baseline severity of illness followed by a chi-square test to calculate the significance of drug use and mortality. Finally, we examined gene expression signatures to explore the drug’s molecular mechanism on AKI. While several drugs demonstrated potential beneficial effects on reducing mortality, most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). One exception was found, ondansetron, a drug without previously identified life-saving effects, has correlation with lower mortality among AKI patients. This association was confirmed in a subsequent analysis using the eICU database. Based on the comparison of gene expression signatures, the presumed therapeutic effect of ondansetron may be elicited through the NF-KB pathway and JAK-STAT pathway. Our findings provide real-world evidence to support clinical trials of ondansetron for treatment of AKI.

Highlights

Acute kidney injury (AKI) is an abrupt and usually reversible decline in glomerular filtration[1], which is attributed to various causes[2,3], is a common disorder and is encountered in various clinical s ettings[4,5]
We aimed to identify drugs already used in clinical practice for treating diseases other than acute kidney injury (AKI) with potential beneficial effects for AKI
Variables associated with intensive care unit (ICU) mortality in patients with AKI

Summary

Introduction

Acute kidney injury (AKI) is an abrupt and usually reversible decline in glomerular filtration[1], which is attributed to various causes[2,3], is a common disorder and is encountered in various clinical s ettings[4,5]. 60% of patients worldwide will suffer from AKI during their intensive care unit (ICU) stay[6]. Patients often already have undergoing AKI when they receive medical attention. Therapy for critically ill patients with AKI requires coordination of a number of treatments across multiple disciplines[11]. We analyzed two publicly available databases (MIMIC III and eICU) of electronic medical records (EMR) from more than 20,000 patients who incurred one or more episodes of AKI during an ICU stay. Our focus was to determine associations between medication use and ICU mortality. Through this analysis, we aimed to identify drugs already used in clinical practice for treating diseases other than AKI with potential beneficial effects for AKI. Variables Warfarin Oxycodone Haloperidol Magnesium Sulfate Heparin Metoprolol Glucagon Lisinopril Captopril Acetaminophen Furosemide Ondansetron Hydralazine Docusate Pantoprazole Hydromorphone Bisacodyl Creatinine average SpO2 mean Platelet average BUN average PTT average Bilirubin average Resprate mean Sapsii Anion gap average Lactate average Potassium average Midazolam Lorazepam Stroke Fentanyl Meropenem Solid tumor Amiodarone Norepinephrine Morphine Coagulopathy

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