Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome.
Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study was to evaluate if terlipressin also improves renal function in patients with ascites without HRS. Twenty-three patients with cirrhosis participated; 15 with nonrefractory ascites were randomized to either terlipressin (N group, n = 11) or a placebo (P group, n = 4), and 8 had refractory ascites and received terlipressin (R group). The glomerular filtration rate (GFR), sodium clearance (C(Na)), lithium clearance (C(Li)), osmolal clearance (C(Osm)), and urine sodium concentration (U(Na)) were assessed before and after the injection of 2 mg of terlipressin or the placebo. GFR increased in the N group (69 +/- 19 versus 92 +/- 25 mL/min, P < 0.005) and in the R group (31 +/- 19 versus 41 +/- 31 mL/min, P < 0.05) after terlipressin. In the N group, terlipressin induced an increase in C(Na) (0.89 +/- 0.21 versus 1.52 +/- 1.45 mL/min, P < 0.05), C(Li) (17.3 +/- 8.9 versus 21.5 +/- 11.6 mL/min, P < 0.05), and C(Osm) (2.10 +/- 0.81 versus 3.06 +/- 2.0 mL/min, P < 0.05). In the R group, terlipressin induced an increase in C(Na) (0.11 +/- 0.18 versus 0.35 +/- 0.40 mL/min, P < 0.05) and C(Li) (5.5 +/- 4.2 versus 9.5 +/- 8.55 mL/min, P < 0.05). U(Na) increased in both groups after terlipressin (P < 0.005). Plasma norepinephrine (P < 0.05) and renin (P < 0.05) decreased after terlipressin. All parameters remained unchanged after the placebo.


CONCLUSIONS
The vasopressin 1 receptor agonist terlipressin improves renal function and induces natriuresis in patients with cirrhosis and ascites without HRS. Vasoconstrictors may represent a novel future treatment modality for these patients.
Krag
Aleksander
A
Department of Gastroenterology, Hvidovre Hospital, Denmark. aleksander.krag@hvh.regionh.dk
Møller
Søren
S
Henriksen
Jens H
JH
Holstein-Rathlou
Niels-Henrik
NH
Larsen
Fin Stolze
FS
Bendtsen
Flemming
F
D001201:Ascites / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006530:Hepatorenal Syndrome; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017483:Receptors, Vasopressin / Q000187:drug effects; D020127:Recovery of Function; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*
D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin