Nutrition, inflammation and insulin resistance in end stage renal disease

• Grant number: 16/03891-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): June 13, 2016
• Effective date (End): September 12, 2016
• Field of knowledge: Health Sciences - Nutrition - Dietetics
• Principal Investigator: Paula Garcia Chiarello
• Grantee: Larissa Rodrigues Neto Angéloco Lourenço
• Supervisor: Alp Ikizler
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Vanderbilt University (VU), United States
• Associated to the scholarship: 12/19475-6 - Protein intake for the acid-base balance in Chronic Kidney Disease patients, in stages 3 and 4, BP.DD

Abstract

Objective: To elucidate the mechanisms by which chronic inflammation and insulin resistance influence the development of protein energy wasting (PEW) in patients with end stage renal disease. The specific aim is to test the hypothesis that inhibiting inflammatory response by administration of Anakinra or increasing insulin sensitivity by administration of Actos will improve net protein metabolism. Methods: A randomized, double-blind, placebo-controlled study. We propose to study a total of 45 subjects with end stage renal disease. At baseline amino acid levels will be checked by HPLC and an arm blood flow will be estimated using capacitance plethysmography. Subjects will then receive a bolus injection of NaH13CO3, Leucine, Phenylalanine and Glucose to prime the CO2, Leucine, Phenylalanine, and Glucose pools. After two hours, we will obtain samples every 10 minutes over 30 minutes for determination of protein turnover. At time 150 minutes, subjects will receive insulin infusion. Amino acid levels will be checked every 10 minutes using HPLC methodology. At time 240 minutes, we will obtain additional blood samples every 10 minutes over 30 minutes for measurement of protein turnover. Blood samples obtained every 5 minutes for glucose and every 10 minutes for amino acid concentrations over the same 30 minute period will allow determination of insulin sensitivity as well as protein metabolism. Once this part of the study is completed, we will randomly assign the subjects to one of the study arms: (a) an injection of Anakinra and matching placebo; (b) oral administration of Actos and matching placebo; (c) both oral administration and an injection of placebo. Each subject will be treated for 2 months. The following parameters will assessed at baseline, week 4 and end of study to evaluate drug effects: biochemical parameters; Inflammatory response; metabolic hormones; oxidative stress markers; plasma amino acids and free fatty acids and body composition. (AU)