CHRONIC METABOLIC-ACIDOSIS DECREASES ALBUMIN SYNTHESIS AND INDUCES NEGATIVE NITROGEN-BALANCE IN HUMANS

Chronic metabolic acidosis has been previously shown to stimulate prot ein degradation, To evaluate the effects of chronic metabolic acidosis on nitrogen balance and protein synthesis we measured albumin synthes is rates and urinary nitrogen excretion in eight male subjects on a co nstant metabolic diet before and during two different degrees of chron ic metabolic acidosis (NH4Cl 2.1 mmol/kg body weight, low dose group, and 4.2 mmol/kg body weight, high dose group, orally for 7 d). Albumin synthesis rates were measured by intravenous injection of [(2)H(5)rin g] phenylalanine (43 mg/kg body weight, 7.5 atom percent and 15 atom p ercent, respectively) after an overnight fast, In the low dose group, fractional synthesis rates of albumin decreased from 9.9+/-1.0% per da y in the control period to 8.4+/-0.7 (n,s,) in the acidosis period, an d from 8.3+/-1.3% per day to 6.3+/-1.1 (P < 0.001) in the high dose gr oup, Urinary nitrogen excretion increased significantly in the acidosi s period (Sigma Delta 634 mmol in the low dose group, 2,554 mmol in th e high dose group). Plasma concentrations of insulin-like growth facto r-I, free thyroxine and tri-iodothyronine were significantly lower dur ing acidosis. In conclusion, chronic metabolic acidosis causes negativ e nitrogen balance and decreases albumin synthesis in humans. The effe ct on albumin synthesis may be mediated, at least in part, by a suppre ssion of insulin-like growth factor-I, free thyroxine and tri-iodothyr onine.