Effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics and sodium homoeostasis in cirrhotic patients with refractory ascites

Systemic arterial vasodilatation has been implicated in the pathogenesis of sodium retention in cirrhosis. Hydrophobic bile acids, which have vasodila tory actions, may be involved. Ursodeoxycholic acid, a hydrophilic bile aci d, could potentially decrease systemic arterial vasodilatation, possibly du e to its antioxidant effects, and improve sodium handling in cirrhosis. The effects of ursodeoxycholic acid on systemic, renal and forearm haemodynami cs, liver function and renal sodium handling were assessed in vasodilated c irrhotic patients with refractory ascites treated with a transjugular intra hepatic porto-systemic shunt (TIPS). Eight cirrhotic patients with refracto ry ascites without TIPS placement served as controls for the sodium handlin g effects of ursodeoxycholic acid. From I month post TIPS, seven patients w ere studied before, after I month of treatment with ursodeoxycholic acid (1 5 mg . day(-1). kg(-1)) and at I month follow-up. Lipid peroxidation produc ts were used as indices of its antioxidant effects. Ursodeoxycholic acid ca used a significant reduction in sodium excretion in both groups (P < 0.05). This, in the post-TIPS patients (urinary sodium excretion: 35+/-8 mmol/day at I month versus 93+/-21 mmol/day at baseline, P < 0.05), was due to a si gnificant increase in sodium reabsorption proximal to the distal tubule (P < 0.05), without any significant changes in systemic, renal or forearm haem odynamics, or in liver function. No significant change in lipid peroxidatio n products was observed. We conclude that: (i) in cirrhotic patients with r efractory ascites, ursodeoxycholic acid causes sodium retention, (ii) the a bnormality in sodium handling in the post-TIPS cirrhotic patients appears t o be the result of a direct effect on the proximal nephron, suggesting that factors other than systemic vasodilatation also contribute to sodium reten tion in cirrhosis, (iii) caution should be exercised in administering ursod eoxycholic acid in cirrhotic patients with ascites.