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Access Type

WSU Access

Date of Award

1-1-2023

Degree Type

Thesis

Degree Name

M.S.

Department

Nutrition and Food Science

First Advisor

Smiti V. Gupta

Abstract

Chronic kidney disease (CKD) afflicts approximately 10% of the world’s population and in recent years, was responsible for 1.4 million deaths globally. High mortality, comorbidities, and immense cost of treatment impair quality of life of patients with CKD. Not only that, the immense cost of lifesaving renal replacement therapy (RRT) is economically burdensome for healthcare systems. Inflammation and oxidative stress present in CKD contribute to the development of cardiovascular disease (CVD) and put patients with end stage kidney disease (ESKD) at the greatest risk CVD. RRT such as HD is a lifesaving treatment for individuals who have progressed to ESKD and conventionally, patients receive a 3 day/week HD frequency for 3–4-hour increments. While 3 day/week HD frequency is standard in higher income countries (HIC) like the United States, 2 day/week HD frequency is common in resource deplete nations due to the immense cost of dialysis, the lack of healthcare programs to subsidize HD, and limited access to HD centers. In recent years, there has been interest in whether 2 day/week HD or even incremental HD is comparable to conventional 3 day/week HD. Cohort studies have suggested less frequent HD could be beneficial in lowering healthcare cost, preserving RKF, and decreasing time patients spend at dialysis centers. On the other hand, more frequent HD shows improved uremic toxin and solute clearance, better volume management, and less need for dietary restrictions in a population already at risk for malnutrition. The lack of clear evidence and randomized controlled trials to support 2 day/week HD over 3 day/week HD leaves the question of what HD frequency is optimal left unanswered. Past work showed modulation of metabolites related to CKD through TRF supplementation in United States and Malaysian cohorts of the Palm Tocotrienols in Chronic Hemodialysis (PATCH) clinical trial. However, metabolomics has yet to be applied to the Bangladesh cohort of the PATCH trial. Unlike previous cohorts who were on conventional HD, participants in the Bangladesh cohort were on both 3 day/week and 2 day/week HD frequency. In this exploratory analysis, a metabolomic approach was utilized with the purpose of evaluating not only the effect of TRF supplementation on metabolites related to inflammation and oxidative stress, but also to investigate plasma metabolomic differences between HD frequencies. In this analysis, levels of amino acids, metabolites related to inflammation, and a uremic toxin precursor were significantly different between HD frequencies at the PATCH trials baseline measurement. After 12 months, differences in plasma metabolomic profiles of ESKD patients on either 3 day/week or 2 day/week HD frequency were instead seen in metabolites related to metabolic pathways. This suggests over time there are fewer differences between HD frequency regimens therefore, lower HD frequency after initial conventional HD may be acceptable. Adjustments in HD frequency over the course of ESKD could spare healthcare resources and may improve QOL for patients. Unlike previous Malaysian and US PATCH cohorts, in the Bangladesh cohort, TRF did not modulate acetoacetate levels over time. This is attributed to greater dyslipidemia (significantly higher TG/HDL ratio and significantly lower HDL) in the Bangladesh cohort compared to previous cohorts. However, TRF did modulate 4-aminobutyrate, a compound identified to be anti-inflammatory and reno-protective, in the 2 day/week hemodialysis group of the Bangladesh cohort how it did in the Malaysian cohort. 4-aminobutyrate is a potential biomarker of TRF supplementation because it was altered similarly in two cohorts. Other key metabolites identified in the Malaysian and United States cohorts which were altered due to TRF supplementation did not show statistical significance due to lower sample size, differences in sample collection, and differences in lipid profiles in the Bangladesh cohort. Finally, strong correlation was seen between metabolomic profiles of the Bangladesh cohort and clinical measures related to kidney disease (lipid profiles, age, anthropometrics, inflammatory markers etc.) which demonstrates the impact environment, age, disease state, lifestyle, and nutrition have on the metabolome. In conclusion, this exploratory metabolomics analysis supports conventional 3 day/week HD frequency and suggests at a longer HD vintage, less frequent HD could be acceptable to ultimately preserve healthcare resources.

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