Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial.
Octreotide seems to have a beneficial effect on variceal bleeding, and long-term administration for the prevention of rebleeding is currently being evaluated. Experimental studies have suggested a beneficial effect of chronic octreotide treatment on renal function, while clinical studies have shown variable effects. Twenty-five cirrhotic patients with portal hypertension were randomized in a double-blind design to placebo or a single subcutaneous dose of a long-acting formulation of octreotide (octreotide-LAR) (20 mg). Renal function tests were performed before dosing and repeated after 30 days. The patients were in sodium steady state at the time of study. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by a constant infusion clearance technique. Renal sodium handling was determined by lithium and sodium clearance measurements. Therapeutic serum levels of octreotide along with a reduction of insulin-like growth factor I (IGF-I) (P <.01) and an increase of IGF binding protein 1 (P <.05) were demonstrated. No effect of octreotide was observed on GFR, ERPF, or filtration fraction (GFR/ERPF). Changes in clearance and extraction fraction of sodium and lithium during octreotide treatment were not significantly different from those of placebo. In addition, no changes in free water clearance, urinary flow rate, or 24-hour Na excretion were demonstrated. A significant increase of mean arterial pressure (+5 mm Hg; P <.01) was observed after treatment with octreotide-LAR. It is concluded that in spite of increased arterial pressure, octreotide-LAR has no significant effect on renal hemodynamics and tubular function in clinically stable cirrhotic patients with portal hypertension.
Ottesen
L H
LH
Centre for Clinical Pharmacology and Department of Medicine V (Hepatology), Aarhus University and University Hospital, Aarhus, Denmark. lo@farm.au.dk
Aagaard
N K
NK
Kiszka-Kanowitz
M
M
Rehling
M
M
Henriksen
J H
JH
Pedersen
E B
EB
Flyvbjerg
A
A
Bendtsen
F
F
D001794:Blood Pressure; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D006728:Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007684:Kidney Tubules / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D009994:Osmolar Concentration; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D003692:Delayed-Action Preparations; D006490:Hemostatics; D006728:Hormones; D018970:Insulin-Like Growth Factor Binding Protein 1; D014867:Water; D019382:Human Growth Hormone; D012964:Sodium; D015282:Octreotide