Mass spectrometry based assessment of the Tryptophan catabolism in Chronic Kidney Disease accelerated heart disease – UROP Spring Symposium 2021

Mass spectrometry based assessment of the Tryptophan catabolism in Chronic Kidney Disease accelerated heart disease

Julian Meza

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Pronouns: He/Him/His

Research Mentor(s): Anna Mathew, Assistant Professor
Research Mentor School/College/Department: Internal Medicine/ Nephrology, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 5 (3pm-3:50pm)
Breakout Room: Room 7
Presenter: 3

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Abstract

Despite the improvements in renal replacement therapies, cardiovascular disease (CVD) remains one of the leading causes of mortality for chronic kidney disease (CKD) patients with a 10-fold increase in mortality rate compared to individuals without CKD. The reason behind this increased risk is not fully explained through classical risk factors; however, non-traditional risk factors like inflammation play an important role in the pathogenesis of CKD atherosclerosis. More specifically, tryptophan metabolism has been linked to inflammation in CKD patients through the kynurenine pathway (KP). In our previous study, tryptophan metabolite levels were associated with incident CVD in CKD patients. With this knowledge, this current study intends to prove that tryptophan catabolism is disproportionately upregulated in atherosclerotic lesions of CKD patients. Plasma and aortic tissue of CKD patients varying in CKD stage will be matched with CVD patients with normal renal function with the objective of finding the disproportionate tryptophan catabolism in atherosclerotic lesions. Aortic tissue will be homogenized and both plasma and tissue lysates will be extracted for tryptophan metabolites using organic solvents. We will use Liquid Chromatography Mass Spectrometry to measure a panel of tryptophan catabolites from these extracts. We expect to find significant differences in KP metabolites in atherosclerotic lesions compared to controls, and correlate lesion KP metabolites to circulating KP metabolites and further prove the strength of using KP metabolites as prospective measures for detecting CVD in CKD patients.

Authors: Julian Meza, Skyelar Herriman, Biaoxin Chai, Anna Mathew
Research Method: Laboratory Research
Research Lab Website: https://mathew.lab.medicine.umich.edu/

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