Effect of experimental azotemia on renal clearance of furosemide in the dog.

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 eight azotemic dogs [blood urea nitrogen (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 seven 30-minute intervals. Initial loading doses were followed by continuous maintenance infusions. For TEA, clearance (1.5 ml/min-g +/- 0.2 S.E.M.) and extraction (E) (0.83 +/- 0.02) are independent of the degree of azotemia. Renal plasma flow (RPF), calculated as CTEA/ETEA, agreed closely with directly measured RPF (2.0 ml/g-min +/- 0.3). RPF was independent of azotemia. To allow for individual differences in the animals in RPF, the ratio CTEA/CF was used. CF (1.07-0.17 ml/min-g) and EF (0.54-0.06) decreased as a linear function of the increase in uremic serum: (see article). Furosemide and its principle metabolite were greater than or equal to 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 two dogs (BUN 170 and 253) CTEA/CF was unrelated to BUN. Thus, the CF decreases proportionately with progressive azotemia and is not related to RBF, exogenous urea or metabolite. This suppression of renal tubular secretion of furosemide may partially account for reduced therapeutic efficacy of furosemide in azotemia.