Renal prostaglandins in cirrhosis of the liver

Abstract

Urinary prostaglandin excretion was studied in 42 patients with liver cirrhosis and in nine control subjects on restricted sodium intake and on bed rest. Creatinine clearance (CCr), sodium excretion (UNaV), plasma renin activity (PRA) and plasma aldosterone were also evaluated. Patients without ascites and ascitic patients without renal failure showed increased urinary excretion of immunoreactive 6-ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha), prostaglandin E2 (iPGE2) and thromboxane B2 (iTXB2) when compared with controls, while immunoreactive PGF2a (iPGF2 alpha) levels did not differ from those in the control group. Patients with functional renal failure (FRF) presented a significant reduction of vasodilator prostaglandins but urinary excretion of iTXB2 was higher than in controls. On the whole, cirrhotic patients with higher urinary excretion of prostaglandins had normal or nearly normal PRA and aldosterone levels. i6-keto-PGF1 alpha and iPGE2 inversely correlated with PRA and aldosterone. The relationship between i6-ketoPGF alpha alpha and CCr was found to be highly significant in cirrhotic patients but not in the control group. On the other hand, iPGE2 significantly correlated with UNaV and with the fractional excretion of sodium (FENa). We concluded that: (a) enhanced renal prostaglandin synthesis in cirrhosis, inversely related to PRA and aldosterone, may be dependent on volume status; and (b) preserved renal function in these patients is associated with the ability to synthesize prostacyclin and PGE2.

Increased renal and vascular cytosolic phospholipase A2 activity in rats with cirrhosis and ascites

“…Patients with cirrhosis have high urinary excretion of 2-3-dinor-6-ketoprostaglandin F 1a , a metabolite of prostaglandin I 2 thought to represent an index of systemic prostaglandin I 2 production. 9,10 In spite of this indirect evidence supporting the existence of increased renal and extrarenal production of PGs in cirrhosis, only one recent study has directly assessed the activity of the enzymes involved in PG synthesis. 11 Phospholipase A 2 (PLA 2 ), which hydrolyzes membrane phospholipids at the sn-2 position, has been shown to be the rate-limiting enzyme in eicosanoid production in most cell types.…”

The Hepatorenal Syndrome

“…Glypressin or octapressin induces reversion of the hyperdynamic circulation, reduces plasma angiotensin and catecholamine levels and increases diuresis and natriuresis [66-681. Renal prostaglandins play an important role in the preservation of renal function in all situations with elevated plasma levels of renin, angiotensin, noradrenaline or vasopressin, such as dehydration, congestive cardiac failure, shock or decompensated liver disease. In the latter situation urinary excretion of prostaglandin E2 (PGE2) and prostacyclin metabolites (6-0x0-PGFI,) are usually increased [39,[69][70][71][72][73]. The mechanism for increased synthesis is unknown, but is likely to be secondary to the increased levels of the vasoconstrictors, many of which have been shown to cause prostaglandin formation in vitro or in vivo.…”

Mineralocorticoid receptor antagonists as diuretics: Can congestive heart failure learn from liver failure?

“…1). In an attempt to normalize EABV, plasma levels of renin, aldosterone, angiotensin II, norepinephrine and vasopressin will be elevated, resulting in an increase in cardiac output [25–27]. These hemodynamic alterations will lead to renal sodium and water retention and ultimate critical plasma volume expansion and edema formation [24].…”