[Growth and protein metabolism in chronic metabolic acidosis from experimental renal insufficiency].

Abstract

Two studies of uremia-induced chronic metabolic acidosis (CMA) were carried out to determine: 1) the level of acidosis beyond which growth failure occurs; 2) the protein metabolism anomalies which are associated with growth failure. Rats rendered uremic by subtotal nephrectomy were fed a diet containing sufficient protein amounts (30% casein) to induce CMA. CMA was left uncorrected in half the rats (group A) and was corrected by administration of bicarbonate in the other half (group B). 1) Fifty-two group A rats were compared with 52 group B rats matched for renal function. Results showed that a) CMA failed to reduce food intake; b) weight gain decreased only when CMA was profound (pH < 7.20) whereas reductions in length gain occurred at less severe levels of acidosis (pH < 7.25) suggesting that bone may be more susceptible to CMA than muscle mass. 2) Protein fractional synthesis rate was evaluated in skeletal muscle after a flooding dose of 3H-phenylalanine in group A rats (pH 7.22 +/- 0.01, HCO3-: 15.2 +/- 0.8 mmol/l) and group B rats matched for renal function. Values were identical in both groups (10.4 +/- 0.5 vs 10.8 +/- 0.5%/day). However, fractional muscle protein accretion rate was decreased in group A rats. These data demonstrate that CMA-associated growth failure in uremia is due to increased breakdown of protein with no change in protein production.