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

Abstract

Systemic arterial vasodilatation has been implicated in the pathogenesis of sodium retention in cirrhosis. Hydrophobic bile acids, which have vasodilatory actions, may be involved. Ursodeoxycholic acid, a hydrophilic bile acid, could potentially decrease systemic arterial vasodilatation, possibly due to its antioxidant effects, and improve sodium handling in cirrhosis. The effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics, liver function and renal sodium handling were assessed in vasodilated cirrhotic patients with refractory ascites treated with a transjugular intrahepatic porto-systemic shunt (TIPS). Eight cirrhotic patients with refractory ascites without TIPS placement served as controls for the sodium handling effects of ursodeoxycholic acid. From 1 month post TIPS, seven patients were studied before, after 1 month of treatment with ursodeoxycholic acid (15 mg.day-1.kg-1) and at 1 month follow-up. Lipid peroxidation products were used as indices of its antioxidant effects. Ursodeoxycholic acid caused 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 1 month versus 93+/-21 mmol/day at baseline, P<0.05), was due to a significant increase in sodium reabsorption proximal to the distal tubule (P<0.05), without any significant changes in systemic, renal or forearm haemodynamics, or in liver function. No significant change in lipid peroxidation products was observed. We conclude that: (i) in cirrhotic patients with refractory ascites, ursodeoxycholic acid causes sodium retention, (ii) the abnormality in sodium handling in the post-TIPS cirrhotic patients appears to be the result of a direct effect on the proximal nephron, suggesting that factors other than systemic vasodilatation also contribute to sodium retention in cirrhosis, (iii) caution should be exercised in administering ursodeoxycholic acid in cirrhotic patients with ascites.

Effects of Ursodeoxycholic Acid on Splanchnic and Systemic Hemodynamics

“…This resulted in a slight but insignificant reduction in MAP, similar to recent findings from cirrhotic patients [14]. The decrease in DBP was not related to any impairment in the function of the myocardium or the sino-atrial node, as previously described for hydrophobic bile acids [15, 16].…”

Bile acids and cardiovascular function in cirrhosis

“…There was no change in these systemic haemodynamic parameters, heart rate or mean arterial pressure during or after the end of the treatment, but the authors noted a decrease in sodium clearance and weight gain in all patients, concluding that UDCA led to sodium retention. 88 More recent studies have yielded similarly conflicting results. Thus, Schiedermaier et al 89 reported a decrease in diastolic blood pressure but not portal flow in a small human cross-over study, while Yang et al 90 described a reduction in portal pressure due to diminished intrahepatic resistance in a rat model.…”

Chronic administration of ursodeoxycholic acid decreases portal pressure in rats with biliary cirrhosis

“…In fact, studies on the effects of chronic administration of UDCA on systemic haemodynamics are still limited. In healthy volunteers, 4 weeks of UDCA (750 mg/day) treatment induced a slight decrease in MAP [51]; however, MAP, heart rate, cardiac output and systemic vascular resistance were not changed by treatment for 1 month with UDCA (15 mg · kg −1 of body weight · day −1 ) in patients with cirrhosis and refractory ascites [20]. In our present study, treatment for 1 month with UDCA (50 mg · kg −1 of body weight · day −1 ) also did not change mesenteric blood flow and MAP in BDL rats.…”

“…Some peripheral effects of chronic UDCA treatment have been reported in cirrhosis [18][19][20]; however, the effects of UDCA in cirrhotic livers are still unclear. Therefore the aim of the present study was to investigate the effects of chronic UDCA administration in the livers of rats with biliary cirrhosis.…”