Characterization of Renal Prostaglandin E Responsiveness in Decompensated Cirrhosis: Implications for Renal Sodium Handling

Abstract

1. It has been suggested that endogenous renal prostaglandin E (PGE) constitutes a determinant of renal haemodynamics and renal sodium handling in patients with cirrhosis. We have accordingly assessed the effects of augmenting endogenous prostaglandins on renal function. We utilized water immersion to the neck since previous studies demonstrated that the redistribution of blood volume and concomitant central hypervolaemia thus induced produces a prompt and marked augmentation of PGE excretion in normal man. 2. Thirteen cirrhotic patients were studied twice while in balance on a daily 10 mmol of sodium/100 mmol of potassium diet during control and during water immersion. Urinary PGE was determined hourly for 6 h. 3. Cirrhotic patients manifested a wide continuum of responses characterized by either a sluggish or barely discernible natriuretic response (n = 5) or an appropriate natriuretic response (n = 8). 4. Water immersion to the neck resulted in a highly significant increase in mean UPGEV, which was threefold that manifested by normal subjects studied under identical conditions. Furthermore, cumulative sodium excretion during immersion correlated with PGE excretion (P less than 0.05). 5. These findings, together with the results of studies utilizing prostaglandin synthase inhibitors, are consistent with the postulate that renal PGE may play a role in the alterations of renal function in decompensated cirrhosis.

Pathogenesis of Renal Sodium Handling in Cirrhosis

“…Epstein et al [41] have utilized water immersion to the neck, an experimental maneuver that redistributes blood volume with concomitant central hypervolemia and enhances PGE excretion in normal man. They demonstrated that decompensated cirrhotic patients manifested an increase in mean PGE excretion that was 3-fold greater than that observed in normal sub jects studied under identical conditions [46]. This was attended by a marked natriuresis and an increase in cre atinine clearance.…”

Urinary Excretion and Glomerular Synthesis of Prostaglandin E₂ and Prostaglandin F_2α in Cirrhotic, Non-Ascitic Rats: The Effects of Sodium Overload

“…Although several neurohumoral alterations have been described in patients with well-established hepatic cirrhosis [3][4][5][6], it is possible that the physiopathological changes observed are not the same as those occurring in earlier stages of the disease. In fact, some results from cirrhotic patients [7] or from nonascitic cirrhotic rats [8] are not absolutely comparable to those previously de scribed.…”

“…The urinary excretion of PGE2 has been re ported to be increased in ascitic cirrhotic patients [11,12] and cirrhotic dogs [13] with normal renal function, and it has been proposed that PGE2 protects the renal function from the action of the different vasoconstrictor sub stances which appear to be increased in cirrhosis [5], However, normal urinary excretion of PGE2 has also been described in cirrhosis [7,8] and there is not enough information available about urinary PGE2 in early stages of the disease. Moreover, the fact that PGE2 synthesized by the different renal structures could have different physiological actions [9] has never been considered in hepatic cirrhosis.…”

Beneficial Effect Polyunsaturated Fatty Acid-Supplemented Diet on Altered Composition of Plasma Fatty Acids in Patients with Liver Cirrhosis

“…Prostanoids formed in the liver control several functions of hepatocytes such as glycogenolysis [3] and DNA synthesis [4]. Hepatorenal syndrome and ascites retention, which are frequently recognized in cirrhotics, are also suggested to be related to prostanoid formation [5,6].…”