Contribution of the urea appearance rate to diuretic-induced azotemia in the rat

Studies were performed to evaluate the contribution of the urea appearance rate to the elevated plasma urea concentration found during diuretic-induced sodium depletion. Negative sodium balance of -1162 + 29 microEq/100 g body wt was induced over a four day period by the administration of furosemide, 20 to 30 mg/kg/d i.p., to rats ingesting a sodium free diet. When compared with sodium replete controls, sodium depletion significantly increased the plasma urea concentration (65.0 +/- 3.1 vs. 26.4 +/- 1.1 mg/dl) through both an increase in the urea appearance rate (160 +/- 5.2 vs. 125 +/- 3.5 mg/day/100 g body wt), and a decrease in the urea clearance rate (1.99 +/- 0.14 vs. 3.16 +/- 0.12 ml/min/kg). The urea appearance rate increased on the first day of diuretic administration, remained elevated three days after stopping diuretics, rapidly returned to control levels after sodium repletion, and was significantly correlated with the magnitude of sodium deficit. Similar results were obtained when diuretic-induced sodium depletion was produced in adrenalectomized animals. After four days of sodium depletion the plasma concentration was increased for some amino acids but not for the plasma total amino acid, nitrogen concentration. The results indicate that sodium depletion increases the urea appearance rate through a mechanism that is independent of adrenal function. Thirty to sixty percent of the elevation in plasma urea concentration that occurs in the rat during diuretic-induced sodium depletion can be accounted for by an enhanced urea appearance rate.