RENAL EFFECTS OF A URODILATIN INFUSION IN PATIENTS WITH LIVER-CIRRHOSIS, WITH AND WITHOUT ASCITES

This study reports the effects of a short-term (60 min) low-dose (20 n g.kg(-1).min(-1)) infusion of synthetic urodilatin (URO) in patients w ith liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrh otic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover desi gn. Renal hemodynamics were estimated by a clearance technique using r adioactive tracers, and tubular handling of sodium was evaluated by th e lithium clearance method. The renal effects of URO were characterize d by a significant increase in urine sodium excretion rate (U-Na) and urine flow rate (V) in the cirrhotic patients without ascites (U-Na: 1 73%; V: 94%) and with ascites (U-Na: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-prox imal fluid delivery), and fractional excretion of lithium increased, f ractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting i ncreased delivery of isotonic fluid from the proximal tubule during UR O infusion. In addition, a significant decrease in fractional distal t ubular sodium reabsorption contributed to the natriuresis. In conclusi on, URO improved sodium and urine output in cirrhotic patients with an d without ascites by enhancing fluid delivery from the proximal tubule s in addition to inhibiting fractional sodium reabsorption in the dist al nephron.