There are currently more than 300,000 patients receiving chronic dialysis therapy in the United States and the life expectancy for these patients are only 1/3 to 1/6 of those for the general population. Chronic inflammation, a highly prevalent condition in hemodialysis patients, is a powerful independent predictor of hospitalization and death in this patient population. Studies have suggested that pro-inflammatory cytokines, the primary mediators of inflammatory response leading to muscle wasting lead to a unique form of protein and energy malnutrition, which can be termed """"""""uremic wasting"""""""". Currently, there are no established interventions to ameliorate the adverse effects of chronic inflammation in dialysis patients. Omega-3 fatty acids are essential for normal growth and development and have been shown to influence coronary artery disease, hypertension, arthritis, inflammatory disorders, and cancer. Studies have shown that omega-3 fatty acid supplementation, particularly with EPA, may reduce pro-inflammatory cytokine production and/or alleviate symptoms related to cardiovascular disease, arthritis, and inflammatory bowel disease. EPA has also been shown to attenuate protein breakdown by downregulating the increased gene expression of key regulatory components of the ubiquitin-proteosome pathway in skeletal muscle of patients with cancer. The overall goal of this grant application is to examine the role of EPA supplementation in ameliorating the inflammatory state of uremia and the related muscle protein catabolism associated with this disease state. We hypothesize that if administered for a period of 3 months, EPA will improve the chronic uremic inflammation and the muscle protein breakdown associated with uremia. We will conduct a randomized, placebo-controlled trial with administration of EPA over 3 months in chronically inflamed hemodialysis patients to test these hypotheses by the following aims:
Specific Aim 1 : To determine the effects of EPA administration on the inflammatory state as measured by: Pro- inflammatory cytokine production capacity, acute phase response and plasma pro-inflammatory cytokine concentrations.
Specific Aim 2 : To determine the effects of EPA administration on protein metabolism as measured by whole body and muscle protein turnover utilizing stable isotope methodology (primary outcome measure) and serum concentrations of nutritional biomarkers.
One of the most important factors responsible for the poor survival of chronic hemodialysis patients is a form of malnutrition termed as """"""""uremic wasting"""""""", which is manifested by progressive loss of muscle mass. Chronic inflammation is also common in dialysis patients and has been linked to uremic wasting. We propose to test if reducing inflammation with an anti-inflammatory treatment (Omega-3 fatty acids in this case) will reduce inflammation and muscle loss in dialysis patients.
