A high proportion of maintenance hemodialysis (MHD) patients have protein-energy malnutrition (PEM), which is a powerful predictor of high morbidity and mortality. Although inflammation may contribute to PEM, low dietary protein intake (DPI) is often a contributing factor. The usual DPI of MHD patients is about 1.0 g protein/kg/day, whereas expert groups recommend = 1.20 g protein/kg/day. However, these recommendations are based upon few studies, often of insufficient duration, that were usually carried out with obsolete types of dialysis therapy. This project has two primary aims: Study 1. To assess dietary protein requirements in clinically stable MHD patients. It is hypothesized that the average DPI that will maintain nitrogen balance is 1.00 g protein/kg/day, but that a safe intake that maintains balance in almost all MHD patients is about 1.25 g protein/kg/day. Study 2. To test the hypothesis that in clinically stable MHD patients with PEM, treatment for 5 months with a DPI of 1.30 g/kg/day, but not 1.00 g/kg/day, is associated with a significant increase in urea-free total body nitrogen (TBNuf). In Study 1, 9 patients will be studied in a clinical research center while they are fed, in random order, the following 5 DPIs, each for 17 days: 0.60, 0.80, 1.00, 1.15 and 1.30 g/kg/day. Energy intake for each patient will be based on their indirect calorimetry. The key outcome measure is nitrogen balance. We will assess the effects of these DPIs on total body (13C-leucine) protein synthesis and degradation and 13C-leucine oxidation during fasting and feeding, plasma amino acids, dialysate amino acids, peptides and proteins, and body composition (anthropometry, dual x-ray photon absorptiometry (DXA)). We will attempt to define more precisely the relationships between urea nitrogen appearance (UNA), protein nitrogen appearance (PNA) and DPI and investigate the validity of urea kinetic equations for estimating UNA, PNA, DPI and urea pools. In Study 2, 70 MHD outpatients will be randomly assigned to a DPI of 1.00 or 1.30 g/kg/day for 5 months each, utilizing dietary counseling and food supplements. Before and after these 5 months, total body protein will be assessed by TBNuf, body cell mass (TBK), and other components of body composition using anthropometry, DXA, and near infra-red interactance.
