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Evaluating the effect of Ondansetron on Reducing ICU Mortality in Patients with Acute Kidney Injury

Guo, Xiaojiang (2021) Evaluating the effect of Ondansetron on Reducing ICU Mortality in Patients with Acute Kidney Injury. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Acute kidney injury (AKI) is an abrupt decline in glomerular filtration, which is attributed to various causes, and greatly increased the mortality of patients. The purpose of this study was to identify medications that provide potentially beneficial effects on decreasing mortality of AKI patients. This was a retrospective cohort study using electronic medical record data of AKI patients in intensive care unit (ICU) and the endpoint outcome was patient mortality in ICU. We evaluated the medical records from two ICU databases, MIMIC III and eICU, to find factors with potential effect on reducing ICU mortality. We used logistic regression to investigate associations between medications received and mortality in AKI patients from the MIMIC III database. Drugs associated with lower death rates were validated using the eICU database. We afterwards used acute physiology age chronic health evaluation (APACHE) predicted mortality for matching of the patient’s baseline severity of illness with R package Match It function “matchit”. A chi-square test to calculate the significance of drug use and mortality was followed. Several drugs showed potential beneficial effects on reducing mortality, and most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). Ondansetron, not previously known as a life-saving drug, showed potential beneficial effect on reducing ICU mortality for AKI patients. This association was confirmed in a subsequent analysis using eICU database. Gene Expression Signature was used to explore the molecular mechanism of the drugs on AKI. The therapeutic effect of ondansetron may be elicited through the modulation of NF-KB pathway and JAK-STAT pathway based on the analysis of gene expression signatures. In this study, we identified several drugs associated with lower mortality following AKI and discovered a potential novel indication for an antiemetic drug, ondansetron. Our findings provide real-world evidence to support clinical trials of ondansetron for AKI treatment.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Guo, Xiaojiangxig53@pitt.eduxig53
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKirisci, Leventlevent@pitt.edu
Committee CoChairKane-Gill, Sandrakane-gill@pitt.edu
Thesis AdvisorWang, Lirongliw30@pitt.edu
Committee MemberBertz, Richardrichard.bertz@biohavenpharma.com
Committee MemberWang, Junmeijunmei.wang@pitt.edu
Date: 13 May 2021
Date Type: Publication
Defense Date: 23 March 2021
Approval Date: 13 May 2021
Submission Date: 5 April 2021
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 66
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Acute kidney injury; Ondansetron; Electronic Medical Records; ICU; Mortality
Date Deposited: 13 May 2021 20:10
Last Modified: 13 May 2021 20:10
URI: http://d-scholarship.pitt.edu/id/eprint/40507

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