The nutritional adequacy of low-protein diets (LPD) and the mechanism for successful adaptation in normal subjects and CRF patients have not been carefully examined. Unfortunately, nitrogen balance (BN) only measures overall response without revealing metabolic adjustments nor whether long- term accommodation to an inadequate protein intake will occur after loss of body protein. In normal subjects, successful adaptation to LPD includes a reduction in amino acid oxidation (without a decrease in protein synthesis and/or degradation) yielding more efficient use of protein. Currently, the mean requirement for normal subjects (0.6 g ketoacids (VLPD-EAA or VLPD-KA) are being used in patients with CRF, but factors in CRF or the supplement may change the adaptive response to LPD. In rats, uremic acidosis increases protein degradation, branch-chain amino acid (BCAA) oxidation and nitrogen excretion. Energy metabolism also affects protein metabolism in experimental uremia. We therefore, plan to assess the utility of the reciprocal pool method for determining BCAA and protein metabolism and to compare results obtained using L[1-13C] leucine and [1-13C] valine (Specific Aims a and 2). We will then compare the short- and long-term (6 months) adaptive response of CRF and normal subjects to different levels of dietary protein using BN, BCAA turnover, calorimetry and the double-labeled water technique (Specific Aims 3 and 4). To assess the nutritional response to VLPD-KA, the optimal tracer technique will be determined and then short- and long-term adaptive responses compared to CRF patients consuming a conventional LPD (Specific Aims 5 and 6). If a nutritional advantage is found with the VLPD-KA diet, it will be compared to a VLPD-EAA regimen (Specific Aims 7 and 8). Finally, the influence of the metabolic acidosis of uremia on the nutritional responses of CRF patients will be examined (Specific Aims 9). This nutritional responses of CRF patients will be examined (Specific Aims 9). This comprehensive evaluation should provide insight into mechanisms of adjustment to and nutritional requirements of normal subjects and CRF patients, and will identify factors that may modify protein requirements, (i.e. energy expenditure or acidosis).

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040907-02
Application #
3241355
Study Section
Nutrition Study Section (NTN)
Project Start
1990-09-01
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Mitch, W E (2000) Mechanisms accelerating muscle atrophy in catabolic diseases. Trans Am Clin Climatol Assoc 111:258-69; discussion 269-70
Mitch, W E (2000) Dietary therapy in uremia: the impact on nutrition and progressive renal failure. Kidney Int Suppl 75:S38-43
Maroni, B J (1998) Impact of chronic renal failure on nitrogen metabolism. Miner Electrolyte Metab 24:34-40
Price, S R; Reaich, D; Marinovic, A C et al. (1998) Mechanisms contributing to muscle-wasting in acute uremia: activation of amino acid catabolism. J Am Soc Nephrol 9:439-43
Maroni, B J; Staffeld, C; Young, V R et al. (1997) Mechanisms permitting nephrotic patients to achieve nitrogen equilibrium with a protein-restricted diet. J Clin Invest 99:2479-87
Maroni, B J (1997) Protein restriction and malnutrition in renal disease: fact or fiction? Miner Electrolyte Metab 23:225-8
Maroni, B J; Mitch, W E (1997) Role of nutrition in prevention of the progression of renal disease. Annu Rev Nutr 17:435-55
Maroni, B J; Tom, K; Masud, T et al. (1996) How is lean body mass conserved with the very-low protein diet regimen? Miner Electrolyte Metab 22:54-7
Tom, K; Young, V R; Chapman, T et al. (1995) Long-term adaptive responses to dietary protein restriction in chronic renal failure. Am J Physiol 268:E668-77
Masud, T; Young, V R; Chapman, T et al. (1994) Adaptive responses to very low protein diets: the first comparison of ketoacids to essential amino acids. Kidney Int 45:1182-92

Showing the most recent 10 out of 18 publications