Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia

Abstract

To maintain nitrogen equilibrium when prescribed a low protein diet (LPD), metabolic adaptations occur involving a reduction protein turnover, principally decreased muscle protein degradation. Studies suggest that in patients with chronic renal failure (CRF) uncomplicated by metabolic acidosis (MA), these adaptive responses are intact. Because MA stimulates muscle proteolysis, this study examined the hypothesis that in CRF complicated by MA, the adaptation to LPD may be impaired, inducing a nitrogen wasting state. Six adults with CRF (mean GFR: 12.8 +/- 1.5 ml/min) and MA (mean serum bicarbonate: 17.0 +/- 1.0 mM/liter) receiving an unrestricted diet (protein intake: 1.2 g/kg body wt/day) were converted to an isocaloric LPD (protein: 0.6 g/kg body wt/day). Two weeks later total urinary nitrogen losses decreased, but skeletal muscle protein catabolism (SMPC), assessed from the urinary 3-methyl histidine:creatinine ratio, increased, demonstrating impairment in the adaptive down-regulation of SMPC. The LPD was continued for a further two weeks and MA was corrected with oral sodium bicarbonate (mean serum bicarbonate: 24.3 +/- 1.2 mM/liter). Correcting MA decreased SMPC to a level below that measured prior to protein restriction. The decreased SMPC was paralleled by further decreases in urinary nitrogen losses, confirming that MA impaired nitrogen utilization. It is concluded that MA can override the expected metabolic adaptive response to a LPD. The associated impairment of nitrogen utilization not only diminishes the efficacy of the diet, but also accelerates the loss of lean body mass.

Effect of Dietary Protein Intake on Serum Total CO2 Concentration in Chronic Kidney Disease

“…In one study in humans with severe CKD, serum [HCO 3 Ϫ ] was notably higher when the patients were compliant with a very low-protein diet (0.3 g/kg body weight) supplemented with ketoanalogs of amino acids (9). In two other studies in humans, serum [total CO 2 ] did not increase significantly after a 50% reduction in protein, but both studies contained very few subjects (10,11). The best data supporting an effect of protein restriction on body alkali stores in CKD come from a partial nephrectomy rat model (12).…”

Effects of Parenteral Infusion of Amino Acid Solutions in Acid-Base Balance in Patients with Advanced Chronic Renal Failure

“…On the contrary the correction of metabolic acidosis increases albumin synthesis [8] and decreases protein catabolism [7,16]. This is important since, considerable protein restriction in CKD patients does not retard the progression of renal failure while it might probably lead to malnutrition.…”

“…Metabolic acidosis, even if it is mild, is related both to negative nitrogen balance [15] and enhanced protein catabolism [16] while chronic metabolic acidosis suppresses albumin synthesis, the most sensitive and early predictor of malnutrition in patients with CKD. On the contrary the correction of metabolic acidosis increases albumin synthesis [8] and decreases protein catabolism [7,16].…”

Prävention von Knochenkomplikationen bei Patienten mit chronischer Niereninsuffizienz (2. Teil)

“…Eine Azidose erhöht die katabole Stoffwechsellage der Skelettmuskulatur über eine Erhöhung von Kortisol und eine Erniedrigung von IGF-I, was zu einem Einschmelzen von Muskulatur und zu Muskelschwäche führt [23] 3. Anorexigener Effekt Dadurch wird der oft bereits prekäre Ernäh-rungszustand noch verschlimmert.…”