The ~350,000 maintenance hemodialysis (MHD) patients in the USA have an unacceptably high mortality rate of 20-25% per year. Almost half of all deaths are assumed cardiovascular (CV). Because markers of malnutrition-inflammation-cachexia syndrome (MICS) such as hypoalbuminemia of <3.8 g/dL, rather than traditional CV risk factors, are among the strongest predictors of early death and because MICS appears to be closely related to oxidative stress (SOX) in MHD patients, modulating the MICS/SOX axis via nutritional interventions may be the key to improving outcomes in these individuals. Hypoalbuminemia <3.8 g/dL is observed in almost half of all MHD patients and appears associated with anorexia, wasting, SOX, endothelial dysfunction, CV disease and several fold increase in mortality. We hypothesize that the MICS can be significantly corrected by a simple in-center oral nutritional support with anti-inflammatory and antioxidant properties combined with an appetite stimulant with anti-inflammatory properties, leading to improved clinical and nutritional outcome measures in MHD patients. In the spirit of PA-06-113 (Pilot and Feasibility Clinical Research Grants in Kidney or Urologic Diseases) we propose a pilot/feasibility randomized placebo-controlled clinical trial with a 2x2 factorial design and a low-priced but efficient operational system in 8 to 10 DaVita dialysis facilities in Los Angles area. During this 2-year pilot/feasibility study, we will test whether our proposed interventions are safe and can improve hypoalbuminemia and other relevant outcomes in 80 MHD patients. Subjects will be adult MHD patients with a serum albumin <3.8 g/dL. The nutritional support arm will include a combination of 2 oral nutritional supplements; i.e., Nepro, tailored for malnourished MHD patients; and Oxepa, designed for sick patients with inflammation and oxidative stress; or their placebos. The appetite stimulating arm will include pentoxifylline 800 mg thrice weekly or its placebo. Both interventions are administered thrice weekly during routine hemodialysis for 16 weeks. Nutritional, inflammatory and oxidative measures, endothelial function, coronary artery calcification, quality of life and other clinical measures will be obtained pre-, during, and post-intervention. The safety and tolerability of the intervention, the feasibility of the study design, and the measurability of the outcomes will be examined. of Research to Public Health: Testing the effect of short-term nutritional interventions with anti-inflammatory, anti-oxidative and appetite stimulating properties on the nutritional status, quality of life, and cardiovascular measures in dialysis patients may lead to improving clinical outcomes in this patient population in the USA and throughout the world. Findings obtained through this study may help improve clinical outcomes in 20 to 40 million Americans from other populations with chronic disease states and poor survival such as those with heart failure, terminal malignancy, and AIDS or Geriatric populations. ? ? ?
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