EFFECT OF EXPERIMENTAL AZOTEMIA ON RENAL CLEARANCE OF FUROSEMIDE IN DOG

Abstract

The clearance of furosemide (F), whose renal tubular transport shares the classical characteristics of the organic acid system, was determined in dogs with varying degrees of azotemia and compared with tetraethylammonium (TEA), an organic base. Two normal and 8 azotemic dogs [blood urea N (BUN), 12-273] were studied. Azotemia was produced by bilateral uretero-venous anastomoses. The left renal vein and ureter were cannulated and renal blood flow (RBF) was measured by electromagnetic flowmeter. Simultaneous left renal clearances (C) of subpharmacological doses of TEA-14C and furosemide-14C were determined at 7-30-min intervals. Initial loading doses were followed by continuous maintenance infusions. For TEA clearance (1.5 ml/min .cntdot. g .+-. 0.2 S.E.M.) and extraction (E) (0.83 .+-. 0.02) are independent of the degree of azotemia. Calculated renal plasma flow (RPF), agreed closely with directly measured RPF (2.0 ml/g .cntdot. min .+-. 0.3). RPF was independent of azotemia. To allow for individual differences in the animals in RPF, the ratio CTEA/CF (CTEA= TEA renal clearance, CF=furosemide renal clearance) was used. CF (1.07-0.17 ml/min .cntdot. g) and EF (0.54-0.06) decreased as a linear function of the increase in uremic serum. Furosemide and its principle metabolite were .gtoreq. 97% of the furosemide portion of the radioactivity. The metabolite did not increase with time in either plasma or urine. After acute administration of exogenous urea to 2 dogs (BUN 170 and 253) CTEA/CF was unrelated to BUN. CF decreases proportionately with progressive azotemia and is not related to RBF, exogenous urea or metabolite. This supression of renal tubular secretion of furosemide may partially account for reduced therapeutic efficacy of furosemide in azotemia.