Dissertation
METABOLIC AND GENETIC MARKERS OF FELINE KIDNEY DISEASE
Doctor of Philosophy (PhD), Washington State University
01/2020
Handle:
https://hdl.handle.net/2376/117623
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly administered classes of analgesics to humans and our veterinary species. Unfortunately, their use in cats is often limited by the potential for organ damage, including the kidneys. The most commonly prescribed NSAID in cats is the COX-2 selective drug meloxicam.
Even with a staggeringly high mortality rate secondary to acute kidney disease within our domestic cat population, the biologic and etiologic underpinnings of this predilection are currently unknown. As a result of this important knowledge gap, there are currently no effective preventive measures or diagnostic tools which permit us to identify feline patients at risk for developing acute kidney injury—before it is a problem, thus limiting the possibility of helping both cats and their owners.
The ultimate objective of my research was to identify molecular and genetic biomarkers for monitoring and individualizing meloxicam administration in cats while maximizing the beneficial effects. Using machine-learning algorithms and a pharmacometabolomic approach we identified a urine and a plasma panel of low molecular weight substances that could be used for discriminating saline-treated cats from meloxicam-treated cats. These panels of metabolites could predict cats that would develop meloxicam-induced kidney disease. In addition, an alteration of the genetic architecture (in-frame, tandem exon duplication) of the feline apoptosis inhibitor of macrophages gene was described and seems to be associated with a higher susceptibility of cats to meloxicam-induced kidney toxicity. Based on these findings a novel rapid and robust genotyping assay was developed that could be used to detect cats carrying this genetic alteration. This genetic tool can be used for individualizing the administration of meloxicam, and probably other nephrotoxins in general and has the potential to change the landscape of feline medical practice.
In conclusion, this dissertation describes work to identify a panel of metabolites to monitor meloxicam administration in cats as well as develop a genetic test to identify cats which may be susceptible to meloxicam-induced kidney injury. This work collectively provides abundant novel information regarding meloxicam treatment in cats.
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Details
- Title
- METABOLIC AND GENETIC MARKERS OF FELINE KIDNEY DISEASE
- Creators
- Liam Broughton-Neiswanger
- Contributors
- Nicolas F Villarino (Advisor)Katrina L Mealey (Committee Member)Michael H Court (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 137
- Identifiers
- 99900581809501842
- Language
- English
- Resource Type
- Dissertation