Effect of hyperketonemia on renal ammonia excretion in man

Abstract

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 μmol/kg min for 160 minutes. Urinary ammonia excretion decreased by 35% ( P < 0.001) while urine pH rose slightly from 5.49 to 5.82 ( P < 0.002). Venous pH increased from 7.31 to 7.38 ( P < 0.005) and bicarbonate concentration from 19 to 25 mEq/L ( P < 0.002). Four subjects were restudied with an infusion of Na β-OHB (pH adjusted to 4.4 with the addition of HCl). Venous pH and bicarbonate concentration did not change significantly while urine pH decreased from 5.25 to 4.90 ( P < 0.001). Urinary ammonia excretion fell by 34% ( P < 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 β-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. Urine pH, blood pH, and plasma bicarbonate concentration rose similarly to that observed with Na β-OHB infusion (pH = 7.4). Ammonia excretion declined by 35% ( P < 0.01). We conclude that the acute infusion of beta-hydroxybutyrate in acidemic man inhibits the urinary excretion of ammonia. These results can not be explained by changes in acid-base status, urine pH, renal plasma flow, or glomerular filtration rate. A change in intracellular redox potential may, in part, account for the decline in renal ammonia excretion.