THE INFLUENCE OF MODERATE HYPOALBUMINEMIA ON THE RENAL METABOLISM ANDDYNAMICS OF FUROSEMIDE IN THE RABBIT

1 The present study aimed to investigate the influence of hypoalbumina emia on the pharmacokinetics and pharmacodynamics of furosemide. Hypoa lbuminaemia was produced by repeated plasmapheresis, to attain plasma albumin concentrations of 21.6 +/- 0.9 g l(-1), compared with 33.0 +/- 0.6 g l(-1) in controls (P<0.001). The per cent of bound furosemide i n hypoalbuminaemic rabbits (90.8 +/- 0.7%) was lower than that in cont rol rabbits (97.4 +/- 0.5%, P<0.001). The kinetics of intravenous furo semide (2.5 mg kg(-1)) were studied in control (n = 6) and hypoalbumin aemic rabbits (n = 6). 2 To assess the effect of hypoalbuminaemia on e xtrarenal clearance of furosemide, functional anephria was induced by ligating the renal pedicles of 12 rabbits, which were segregated in tw o groups, with and without hypoalbuminaemia. 3 In the control group, t otal, urinary and metabolic clearances of furosemide were 11.8 +/- 1.0 , 5.0 +/- 0.4 and 6.8 +/- 0.6 ml min(-1) kg(-1), respectively. Compare d with control rabbits, in hypoalbuminaemic rabbits, total clearance o f furosemide increased by 40% (P<0.001), result of the enhancement of furosemide metabolic clearance (Cl-m) from 5 to 10 ml min(-1) kg(-1) ( P<0.01). In hypoalbuminaemic rabbits, urinary excretion of furosemide was reduced by 26% (2451 +/- 115 vs 1818 +/- 134 mu g h(-1), P<0.01). In anephric rabbits, furosemide total clearance was 1.77 +/- 0.12 ml m in(-1) kg(-1), value not affected by hypoalbuminaemia, confirming that the increase in Cl-m induced by hypoalbuminaemia occurs in the kidney s. 4 Compared with controls, in hypoalbuminaemic rabbits, the rate of urinary excretion (142 +/- 9 vs 74 +/- 8 ml h(-1), P<0.001) and the ra te of excretion of sodium (18.6 +/- 0.9 vs 9.9 +/- 0.9 mmol h(-1), P<0 .001) were very much reduced. However, the dose-response curves were n ot different. 5 In conclusion, hypoalbuminaemia is associated with an increase in renal metabolic clearance of furosemide, possibly because of the increase in furosemide unbound concentration, and a decrease in the diuretic/natriuretic effect of furosemide, secondary to a reducti on in furosemide tubular secretion. Thus, albumin facilitates the rena l secretion of organic anions but not their metabolism.