LONG-TERM ADAPTIVE RESPONSES TO DIETARY-PROTEIN RESTRICTION IN CHRONIC-RENAL-FAILURE

Six patients with chronic renal failure (glomerular filtration rate 18 +/- 2 ml/min) underwent two 10-day admissions separated by at least 1 yr of outpatient therapy with a very low-protein diet (VLPD) providin g 0.28 g protein.kg(-1).day(-1) plus an amino acid-ketoacid supplement . During each Clinical Research Center admission, subjects completed a 5-day nitrogen balance (B-N), and whole body protein turnover was mea sured during fasting and feeding using intravenous [1-C-13]leucine and intragastric [5,5,5-H-2(3)]leucine. Outpatient dietary protein compli ance was very good (25 vs. 20 g protein/day or 125% goal), whereas ene rgy intake was only 69% of goal (24 vs. 35 kcal.kg(-1).day(-1)), Durin g the 16 +/- 2 mo of dietary therapy, there were no changes in serum p roteins or anthropometrics. BN after greater than or equal to 1r of di etary therapy was neutral and did not differ from initial values (+0.4 6 +/- 0.20 vs. +0.55 +/- 0.19 g N/day). Similarly, rates of whole body protein synthesis, degradation, and leucine oxidation after long-term therapy with the VLPD regimen did not differ from baseline values, an d neutral BN was maintained by a marked suppression of amino acid oxid ation and postprandial inhibition of protein degradation. This is the first evidence that the compensatory changes in whole body protein tur nover activated in response to dietary protein restriction are sustain ed during long-term therapy.