Sodium-dependent urinary acidification in patients with aldosterone deficiency and in adrenalectomized rats: Effect of furosemide

Urinary acidification during metabolic acidosis and in response to stimulation of sodium-dependent hydrogen ion secretion using furosemide administration was evaluated in 12 patients with hyperkalemic hyperchloremic metabolic acidosis associated with mild chronic renal insufficiency and aldosterone deficiency. During spontaneous metabolic acidosis, the urine of all patients was acidic (pH less than 5.5), but ammonium excretion was markedly reduced (6.6 ± 1.3 μEq/min) comprising only about 20% of net acid excretion (30.5 ± 5.7 μEq/min). Furosemide (80 mg orally) resulted in a further fall in urine pH (from 5.29 ± 0.06 to 4.97 ± 0.09, P < 0.02) and a significant increase in net acid excretion (from 30 ± 5.8 to 38 ± 5.1 μEq/min, P < 0.02) while plasma aldosterone did not change (from 9.8 ± 1.7 to 9.7 ± 1.6 μg/dL). To investigate whether the acute stimulatory effect of furosemide on distal acidification requires some degree of mineralocorticoid activity, studies were conducted in adrenalectomized rats. The fall in urine pH and the increase in net acid excretion elicited by furosemide in adrenalectomized rats were comparable to those observed in adrenal-intact animals (5.37 ± 0.10 v 5.67 ± 0.11 and 0.43 ± 0.08 v 0.41 ± 0.06 μEq/min, respectively). inhibit sodium transport in the cortical collecting tubule, furosemide failed to lower urine pH (6.44 ± 0.23) and to increase net acid excretion (0.07 ± 0.06 μEq/min). These findings demonstrate that furosemide enhances hydrogen ion secretion in the absence of aldosterone provided that sodium-transport in the cortical collecting tubule is not impaired. The data therefore lends support for the notion that this diuretic stimulates urinary acidification by increasing sodium-dependent hydrogen ion secretion in the cortical collecting tubule and that this effect is mineralocorticoid-independent.