The effect of single oral low-dose losartan on posture-related sodium handling in post-TIPS ascites-free cirrhosis.
Post-TIPS ascites-free patients with cirrhosis and previous refractory ascites demonstrate subtle sodium retention when challenged with a high sodium load. This is also observed in pre-ascitic patients with cirrhosis. This phenomenon is dependent on an intrarenal angiotensin II (ANG II) mechanism related to the assumption of erect posture. We investigated whether similar mechanisms were involved in post-TIPS ascites-free patients, by studying 10 patients with functioning TIPS and no ascites. We measured the effect of changing from supine to erect posture on sodium excretion at baseline and after single oral low dose losartan (7.5 mg) which has been shown to blunt proximal and distal tubular sodium reabsorption in pre-ascites. At baseline, the assumption of erect posture produced a reduction in sodium excretion (from 0.30+/-0.06 to 0.13+/-0.02 mmol/min, P=.05), which was mainly due to an increase in proximal tubular reabsorption of sodium (PTRNa) (69.7+/-3.1% to 81.1+/-1.8%, P=.003). The administration of losartan resulted in a blunting of PTRNa (supine 69.7+/-3.1% to 63.9+/-3.9%, P=.01 and erect 81.1+/-1.8% to 73.8+/-2.4%, P=.01), accompanied by an increased distal tubular reabsorption of sodium in both postures, with no overall improvement in sodium excretion on standing. In conclusion, post-TIPS ascites-free patients with cirrhosis exhibit erect posture-induced sodium retention. We speculate that (1) this effect is partly mediated by the effect of ANG II on PTRNa and (2) that the inability of low dose losartan to block the erect posture-induced sodium retention may be related to the erect posture-induced rise in aldosterone which is unmodified by losartan.
Therapondos
George
G
Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Canada.
Hol
Lieke
L
Benjaminov
Fabiana
F
Wong
Florence
F
D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001201:Ascites / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000601:surgery / Q000652:urine; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011184:Postoperative Period; D011187:Posture / Q000502:physiology*; D012964:Sodium / Q000652:urine*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D012964:Sodium; D019808:Losartan