Access Type

Open Access Thesis

Date of Award

January 2014

Degree Type

Thesis

Degree Name

M.S.

Department

Nutrition and Food Science

First Advisor

Pramod Khosla

Abstract

Chronic kidney disease (CKD) is known as a heterogeneous disorder which currently is on the rise and lately has been classified as a public health issues in the United State and worldwide. CKD is an irreversible and progressive disease which can lead to kidney failure, and this is depicted by the advanced stage of the disorder when it reaches the point, that is classified as end stage of renal disease (ESRD) (Stage 5 of CKD) (eGRF <15 mL/min/ 1.73 m2 working capacity), where both organs are in a total or permanent kidney failure. End-Stage renal disease patients, on hemodialysis have been associated to experience an accelerated form of atherosclerosis, which is induced by inflammation, impairment of antioxidant system and elevated oxidative stress. Since the problem effecting ESRD patients is multifactorial, the objective of this investigation is to explore and look at the effects of supplementing with vitamin E-tocotrienol rich fraction (TRF), a micronutrient which has anti-inflammatory, antioxidant, and lipid lower capabilities into tackling these comorbid conditions experienced by this population. Therefore the aims of this investigation will be to explore changes in lipid profiles, inflammatory markers, and oxidative status, as well as look at any changes in metabolomic profiles. It was hypothesized that by supplementing with TRF a vitamin E, for 16 weeks in ESRD patients undergoing hemodialysis, it may help reverse and/or improve, oxidative status, inflammatory markers, increase antioxidants status and improve lipid profiles.

The study was double-blinded, randomized, parallel, placebo-controlled design trial, of 81 adult patients undergoing chronic hemodialysis at Great Lake Dialysis Clinic, Detroit MI, where patients routinely received hemodialysis treatments 3 days a week. These HD patients were randomly divided into two different groups before the nutritional intervention began; a placebo group (n=40) and intervention group TRF (n=41). The patients in the TRF group received 2 x 110 mg/day (220 mg/day) of vitamin E tocotrienol (90 mg of TT and 20 mg of TP) whereas the placebo group patients received 2 x 0.68 mg/day of placebo (0.24 mg of TT and 0.44 mg of TP). Blood samples were collected at baseline, week 8, week 12 and 16 in order to perform biochemical analysis of lipid profiles (TC, TAG, LDL-C, and HDL-C), and then after analyze inflammatory markers, measured using enzymatic kits (CRP, NFκB, IL-6). And last part of the study revolved around metabolomics analysis on the plasma samples using (600MHz) NMR technology, than explore changes in metabolomic profile (biomarkers) in ESRD population.

The study recorded changes and improvement on lipid profiles of ESRD patients. A significant decrease of TAG levels was observed as well as an increase in HDL-C was recorded. The change in TAG levels and HDL-C increase, correlated with the decrease in CETP levels and increase of ApoA1 in the plasma. Other lipid profile like TC and LDL-C observed marginal decreases which were not significant, therefore further detailed analysis is required. In this analysis patients were further divided into four sub-groups to establish links between TRF and statin drugs. It was concluded that based on lipid profiles and metabolomic (NMR) analysis, there seem to be some small correlations of synergism effects when combining Statin drugs with TRF supplements but in order to validate conclusively this minor links, further detailed analysis is required. Study did established that TRF supplementation does trigger a change in ESRD metabolome profile. A correlation between lipid profiles and plasma metabolome shows a significant difference between TRF and placebo groups. Metabolomic profile analysis in TRF and placebo does display a correlation when looking at inflammatory biomarkers to lipid profiles which suggests that plasma metabolites could be used to predict changes in biomarkers. The study did not find any significant changes on inflammatory and oxidative markers. Research into biomarkers of ESRD metabolome when using (Chenomx) did discover and identify eleven biomarkers of importance in human metabolism that observed a significant change due to TRF supplementation when compared to its counterpart placebo group. Therefore in conclusion this investigation has revealed that TRF supplementation does reveal to trigger changes in ESRD metabolome that could be used for disease prediction in HD patients.

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