This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic
urodilatin (URO) in patients with
liver cirrhosis. URO is a
natriuretic peptide. A total of 15 cirrhotic patients with
ascites and nine without
ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using
radioactive tracers, and tubular handling of
sodium was evaluated by the
lithium clearance method. The renal effects of URO were characterized by a significant increase in urine
sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without
ascites (UNa: 173%; V: 94%) and with
ascites (UNa: 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-proximal fluid delivery), and fractional excretion of
lithium increased, fractional proximal tubular
sodium reabsorption decreased, and absolute proximal tubular
sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular
sodium reabsorption contributed to the natriuresis. In conclusion, URO improved
sodium and urine output in cirrhotic patients with and without
ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional
sodium reabsorption in the distal nephron.