Faculty
Medical Sciences
Supervisor Name
Brad Urquhart
Keywords
AKI, nephrotoxicity, metabolite, biomarker, multivariate
Description
Cisplatin is a chemotherapeutic agent complicated by its dose-limiting nephrotoxicity. This commonly presents as acute kidney injury (AKI), which is characterized by a reversible decline in kidney function. AKI is currently diagnosed by increased serum creatinine (SCr) levels, but this rise in SCr is delayed limiting diagnosis to when significant renal damage has already occurred. Currently, there are no known biomarkers capable of predicting or diagnosing early-stage cisplatin-induced AKI. Metabolomics was used to identify novel predictive/early diagnostic biomarkers for cisplatin-induced AKI. We hypothesized that differences in metabolic profiles will be able to predict and/or diagnose cisplatin-induced AKI prior to rise in serum creatinine.
Plasma and urine samples from adult patients were collected at three timepoints of cisplatin therapy: pre-treatment, 24-48h, and 5-14 days post-treatment. Ultra-performance liquid chromatography mass spectrometry was used to measure metabolite abundance. Derivatization assays using molecular tags increased metabolites captured during analysis. Principal component analysis (PCA) was used to visualize metabolic differences between AKI vs. no-AKI groups at each timepoint. S-plots generated from orthogonal partial least squares discriminant analysis (OPLS-DA) identified metabolites responsible for distinguishing groups. Identified metabolites were assessed for relative intensities across therapy timepoints, followed by statistical analysis using GraphPad Prism software.
My project aimed to contribute a panel of biomarkers which will help aid in the earlier clinical diagnosis of cisplatin-induced AKI, ensuring better monitoring of AKI progression, interventions to minimize further renal complications, and facilitate better understanding of drug nephrotoxicity.
Acknowledgements
I would like to thank PhD candidate James Lim and principal investigator Dr. Brad Urquhart for their continued support, expertise and guidance throughout this project. This study received funding support from Western University and the Canadian Institutes of Health Research (CIHR).
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Document Type
Poster
Metabolomic approach for earlier diagnosis of cisplatin-induced acute kidney injury
Cisplatin is a chemotherapeutic agent complicated by its dose-limiting nephrotoxicity. This commonly presents as acute kidney injury (AKI), which is characterized by a reversible decline in kidney function. AKI is currently diagnosed by increased serum creatinine (SCr) levels, but this rise in SCr is delayed limiting diagnosis to when significant renal damage has already occurred. Currently, there are no known biomarkers capable of predicting or diagnosing early-stage cisplatin-induced AKI. Metabolomics was used to identify novel predictive/early diagnostic biomarkers for cisplatin-induced AKI. We hypothesized that differences in metabolic profiles will be able to predict and/or diagnose cisplatin-induced AKI prior to rise in serum creatinine.
Plasma and urine samples from adult patients were collected at three timepoints of cisplatin therapy: pre-treatment, 24-48h, and 5-14 days post-treatment. Ultra-performance liquid chromatography mass spectrometry was used to measure metabolite abundance. Derivatization assays using molecular tags increased metabolites captured during analysis. Principal component analysis (PCA) was used to visualize metabolic differences between AKI vs. no-AKI groups at each timepoint. S-plots generated from orthogonal partial least squares discriminant analysis (OPLS-DA) identified metabolites responsible for distinguishing groups. Identified metabolites were assessed for relative intensities across therapy timepoints, followed by statistical analysis using GraphPad Prism software.
My project aimed to contribute a panel of biomarkers which will help aid in the earlier clinical diagnosis of cisplatin-induced AKI, ensuring better monitoring of AKI progression, interventions to minimize further renal complications, and facilitate better understanding of drug nephrotoxicity.