Disease relevance of Hepatorenal Syndrome

• To evaluate the potential contribution of the vasodilator prostaglandin E2 and the vasoconstrictor metabolite thromboxane B2 to the development of the hepatorenal syndrome, we measured urinary excretion of these products in 14 patients with hepatorenal syndrome and in control populations with acute or chronic liver or kidney failure [1].
• Thromboxane B2 concentration was normal in patients with alcoholic hepatitis (0.12 +/- 0.02 vs. 0.15 +/- 0.03 ng/ml) and minimally increased in acute renal failure (0.18 +/- 0.15 ng/ml), but markedly elevated in hepatorenal syndrome (0.69 +/- 0.15 ng/ml, p less than 0.001) [1].
• When corrected for creatinine clearance, there was a strong correlation between prostanoid excretion and serum bilirubin in subjects with liver disease; there was no difference, however, in the excretion of renal and extrarenal prostanoids between hepatorenal syndrome and severe hepatic decompensation [2].
• Systemic and hepatic hemodynamics and the activity of endogenous vasoactive systems were measured in 66 patients who had cirrhosis with tense ascites and normal serum creatinine levels; measurements were repeated at follow-up in 27 cases in whom hepatorenal syndrome had developed [3].
• CONCLUSION: Renal Doppler ultrasonography can noninvasively identify a subgroup of nonazotemic patients with hepatic cirrhosis who are at high risk for subsequent development of renal dysfunction and hepatorenal syndrome [4].

High impact information on Hepatorenal Syndrome

• Plasma endothelin and the hepatorenal syndrome [5].
• The increase in plasma endothelin-1 and endothelin-3 concentrations in patients with the hepatorenal syndrome is consistent with the hypothesis that these substances have a role in the pathogenesis of the disease [6].
• Dopamine in the hepatorenal syndrome [7].
• Terlipressin-induced vasoconstriction reversed with N-acetylcysteine: a case for combined use in hepatorenal syndrome [8]?
• Liver size, plasma renin activity, and serum sodium concentration are predictors of hepatorenal syndrome occurrence in these patients [9].

Chemical compound and disease context of Hepatorenal Syndrome

• The excretion rate of all metabolites was markedly elevated during the early stages of hepatorenal syndrome and decreased in parallel with creatinine clearance [2].
• Thus, as judged by selective thromboxane inhibition with dazoxiben, thromboxanes are unlikely to be the key renal vasoconstrictor factor in the hepatorenal syndrome [10].
• Therapeutic trial of thromboxane synthesis inhibition in the hepatorenal syndrome [10].
• It is concluded that hepatic decompensation is associated with a progressive increase in prostanoid excretion but that changes in production of prostacyclin or thromboxane A2 are unlikely to be major factors in the pathogenesis of the hepatorenal syndrome [2].
• Improvement in renal function in hepatorenal syndrome with N-acetylcysteine [11].

Biological context of Hepatorenal Syndrome

• Although the prolonged administration of ornipressin combined with plasma volume expansion reverses hepatorenal syndrome, this treatment should be used with great caution in clinical practice because of the risk of ischemic complications [12].
• These results confirm the existence of a well-defined circadian rhythm of AVP in healthy subjects, whereas the hepatorenal syndrome patients present a complete loss of the circadian rhythm [13].
• Some reports have pointed out that serum creatinine levels frequently failed to rise above normal levels even when glomerular filtration rate (GFR) is very low in cirrhotic patients with hepatorenal syndrome [14].
• In patients with hepatorenal syndrome (HRS), 4-hr administration of a vasopressin analog has recently been shown to benefit renal blood flow and renal function [15].
• In three patients with hepatorenal syndrome diuresis was established during dopamine and frusemide infusion, but severe oliguria again reappeared when drug infusion was stopped [16].

Gene context of Hepatorenal Syndrome

• Treatment of hepatorenal syndrome: lessons from the MARS trial [17].
• Immunohistochemical distribution of renal prostaglandin endoperoxide synthase and prostacyclin synthase: diminished endoperoxide synthase in the hepatorenal syndrome [18].
• The renal production of cytochrome P450 metabolites of arachidonic acid is altered in hypertension, diabetes, toxemia of pregnancy, and hepatorenal syndrome [19].
• The release of ET-1 by 8-epi-PGF2 alpha may help to explain the large increases in plasma and urinary concentrations for both ET-1 and 8-epi-PGF2 alpha in patients with hepatorenal syndrome [20].
• Tubular dysfunction, manifested by increased urinary excretion of B2MG, occurs in patients with hepatorenal syndrome and deep jaundice [21].

Analytical, diagnostic and therapeutic context of Hepatorenal Syndrome

• Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine [22].
• To evaluate possible causes of the diminished prostaglandin production in advanced hepatorenal syndrome, prostaglandin endoperoxide synthase and prostacyclin synthase were localized and semiquantitated by immunofluorescence in postmortem, biopsy and nephrectomy renal tissues [18].
• Three patients died after 10, 30 and 40 days due to oesophageal bleeding, encephalopathy or pulmonary infection, whereas one patient underwent an orthotopic liver transplantation when her serum creatinine attained a level of 13 mg/l. In the first patient, hepatorenal syndrome recurred 10 days after stopping the misoprostol treatment [23].
• Effects of a portacaval or peritoneovenous shunt on renin in the hepatorenal syndrome [24].
• In the early stages of hepatorenal syndrome, leukotriene E4 excretion rate was up to 100-fold higher (560 ng/h) than in normals, and fell in parallel with creatinine clearance, indicative of the glomerular filtration rate-dependent renal excretion [25].

References