Long-term adaptive responses to dietary protein restriction in chronic renal failure

Abstract

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) providing 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 (BN), and whole body protein turnover was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Outpatient dietary protein compliance was very good (25 vs. 20 g protein/day or 125% goal), whereas energy intake was only 69% of goal (24 vs. 35 kcal.kg-1.day-1). During the 16 +/- 2 mo of dietary therapy, there were no changes in serum proteins or anthropometrics. BN after > or = 1 yr of dietary therapy was neutral and did not differ from initial values (+0.46 +/- 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, and neutral BN was maintained by a marked suppression of amino acid oxidation and postprandial inhibition of protein degradation. This is the first evidence that the compensatory changes in whole body protein turnover activated in response to dietary protein restriction are sustained during long-term therapy.

Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients

“…Our results are in accordance with previous studies using VLPD þ KA for longer periods of time (Mitch et al, 1982;Walser, 1993;Masud et al, 1994;Tom et al, 1995). Indeed, isotopic studies that evaluated protein metabolism showed that for both shortterm and long-term treatment periods, neutral or positive nitrogen balance is attained in patients receiving a VLPD þ KA, yet energy intake was below the recommended 146 kJ/kg/day (35 kcal/kg/day) (Masud et al, 1994;Tom et al, 1995). Similar results regarding low energy intake and maintenance of nutritional parameters were also observed in the present study.…”

“…Although concern has been raised about the nutritional adequacy of these diets and the risk for the subsequent development of malnutrition (Aparicio et al, 2001) studies have demonstrated that a VLPD þ KA in carefully selected and motivated patients with advanced CKD has no deleterious influence on some nutritional parameters in the predialysis phase of CKD (Mitch et al, 1982;Walser, 1993;Masud et al, 1994;Tom et al, 1995;Aparicio et al, 2001). However, only a few studies have included a control group and patients that were previously following a conventional low protein diet.…”

Mechanisms permitting nephrotic patients to achieve nitrogen equilibrium with a protein-restricted diet.

“…This is not surpris- ing since a HPD is known to stimulate leucine oxidation (12,19) and would obscure the influence of proteinuria.…”

“…The contribution of the formula meal to background 13 CO 2 enrichment was determined on day 9 by collecting expired breath samples during feeding using an identical protocol to that described for the whole-body leucine turnover, except that tracers were not infused (10,19). To minimize its contribution to background 13 CO 2 enrichment, foods with a low 13 C abundance were chosen for the formula meal (20).…”

“…To minimize its contribution to background 13 CO 2 enrichment, foods with a low 13 C abundance were chosen for the formula meal (20). The steady-state 13 CO 2 enrichment measured during the feeding phase of the sham infusion was then subtracted from the plateau 13 CO 2 enrichment measured during the feeding phase of the NaH 13 CO 3 and l -[1-13 C]leucine infusions (10,19).…”