Abstract
Prediction and early detection of kidney damage induced by nonsteroidal anti-inflammatories (NSAIDs) would provide the best chances of maximizing the anti-inflammatory effects while minimizing the risk of kidney damage. Unfortunately, biomarkers for detecting NSAID-induced kidney damage in cats remain to be discovered. To identify potential urinary biomarkers for monitoring NSAID-based treatments, we applied an untargeted metabolomics approach to urine collected from cats treated repeatedly with meloxicam or saline for up to 17 days. Applying multivariate analysis, this study identified a panel of seven metabolites that discriminate meloxicam treated from saline treated cats. Combining artificial intelligence machine learning algorithms and an independent testing urinary metabolome data set from cats with meloxicam-induced kidney damage, a panel of metabolites was identified and validated. The panel of metabolites including tryptophan, tyrosine, taurine, threonic acid, pseudouridine, xylitol and lyxitol, successfully distinguish meloxicam-treated and saline-treated cats with up to 75–100% sensitivity and specificity. This panel of urinary metabolites may prove a useful and non-invasive diagnostic tool for monitoring potential NSAID induced kidney injury in feline patients and may act as the framework for identifying urine biomarkers of NSAID induced injury in other species.
Highlights
We utilized an untargeted metabolomics approach to identify urine low molecularweight (LMW) that could be further studied as biomarker candidates for monitoring during the administration of Non-steroidal anti-inflammatory drugs (NSAIDs) in cats
This study discovered LMWs that are altered by the repeated administration of meloxicam and could be used to detect or predict early adverse effects in cats
It is important to remark that this study provides, untargeted and nonbiased information regarding urinary metabolites, as the hypothesis is not based on pre-selection of potential candidates to be investigated
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are massively used in both veterinary and human patients for treating pain and inflammation with approximately 111 million prescriptions dispensed each year in the U.S alone [1]. Urine biomarkers of NSAID administration in cats study design, data collection and analysis, decision to publish, or preparation of the manuscript
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