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 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.
Carstens
J
J
Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Denmark.
Greisen
J
J
Jensen
K T
KT
Vilstrup
H
H
Pedersen
E B
EB
D000328:Adult; D001201:Ascites / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007684:Kidney Tubules / Q000187:drug effects / Q000503:physiopathology; D008094:Lithium / Q000493:pharmacokinetics / Q000652:urine; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D015290:Second Messenger Systems / Q000187:drug effects
D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D008094:Lithium; D006152:Cyclic GMP