Dual effect of potent diuretics on renal handling of phosphate in man.

Abstract

Inorganic phosphate excretion appeared to reflect changes in reabsorptive activity within the proximal nephron following diuretic administration in man. Intravenous ethacrynic acid and furosemide both resulted in equivalent immediate phosphaturic responses. Phosphate excretion decreased significantly during the second hour after ethacrynic acid was injected when urinary losses were not replaced, but remained unchanged if the body weight was maintained constant by isotonic saline infusion. Phosphate excretion was unchanged during the second hour after the injection of furosemide when volume contraction occurred but increased significantly in the studies with saline repletion. Since ethacrynic acid depressed glomerular filtration rate (GFR) more than furosemide, even when urinary losses were replaced with saline, the quantitative differences between these agents' effects on phosphate excretion probably reflected the depressant effect of ethacrynic acid on GFR. The tendency toward relative phosphate retention during diuretic-induced volume contraction after the introduction of either agent could be reversed by isotonic saline infusion. During saline infusion, ultrafilterable plasma calcium concentrations did not vary reciprocally with phosphate excretion, sodium excretion fell from peak postdiuretic values, and urinary phosphate increased. The suppressive effect of volume depletion on inorganic phosphorus output seems best interpreted as a consequence of concomitantly increased fractional sodium and water reabsorption by the proximal nephron. In contrast, the immediate phosphaturia following the injection of ethacrynic acid or furosemide may reflect primary inhibitory actions of these agents on phosphate reabsorption further distally, possibly at the site in Henle's loop where they exert their major effect on sodium reabsorption, since volume contraction did not affect the magnitude of this immediate phosphaturic response unless GFR decreased concomitantly.