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.