Effect of hyperketonemia on renal ammonia excretion in man.
The effect of DL-sodium beta-hydroxybutyrate (Na BOHB) on urinary ammonia excretion was studied in seven chronically acidemic human subjects. Metabolic acidosis was induced by the ingestion of 0.1 g/kg body weight of ammonium chloride for three days. On the morning of day 4, baseline blood and urine samples were collected during three 30-minute periods. Na BOHB (1 mmol/kg, pH = 7.4) was then infused over 20 minutes, and this was followed by a continuous infusion at the rate of 10 mumol/kg min for 160 minutes. Urinary ammonia excretion decreased by 35% (P less than 0.001) while urine pH rose slightly from 5.49 to 5.82 (P less than 0.002). Venous pH increased from 7.31 to 7.38 (P less than 0.005) and bicarbonate concentration from 19 to 25 mEq/L (P less than 0.002). Four subjects were restudied with an infusion of Na beta-OHB (pH adjusted to 4.4 with the addition of HCI). Venous pH and bicarbonate concentration did not change significantly while urine pH decreased from 5.25 to 4.90 (P less than 0.001). Urinary ammonia excretion fell by 34% (P less than 0.01) despite the decline in urine pH and the absence of change in blood pH and bicarbonate concentration. Three subjects were restudied with sodium bicarbonate (0.52 to 0.85 mEq/min) infusion. Despite similar increases in blood pH and plasma bicarbonate concentration as observed with Na beta-OHB at pH = 7.4, urinary ammonia excretion did not fall significantly. In an attempt to simulate the change in redox potential and NAD+ to NADH ratio that occurred during the metabolism of beta-hydroxybutyrate to acetoacetate, sodium lactate was given to four subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
D000138:Acidosis / Q000150:complications / Q000378:metabolism*; D000328:Adult; D000641:Ammonia / Q000652:urine*; D000643:Ammonium Chloride / Q000009:adverse effects; D004573:Electrolytes / Q000097:blood; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007659:Ketones / Q000097:blood*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D012978:Sodium Oxybate / Q000097:blood / Q000494:pharmacology*
D004573:Electrolytes; D006885:Hydroxybutyrates; D007659:Ketones; D000643:Ammonium Chloride; D000641:Ammonia; D012978:Sodium Oxybate