Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal function is known to be abnormal in patients with cirrhosis. Diminished cortical blood flow due to active renal vasoconstriction is present. Renal prostaglandins, potent vasodilators, could be released by the kidney in an attempt to maintain renal blood flow. This possibility was investigated by measuring the effect of indomethacin, an inhibitor of prostaglandin synthetase, in patients with alcoholic liver disease. Administration of indomethacin reduced the effective renal plasma flow (ERPF) and creatinine clearance by 23% and 19%, respectively (P less than 0.001), and increased serum creatinine by 29% (P less than 0.001). The response to indomethacin was variable (fall in ERPF (+)7.8% to (-)67%), but was greatest in patients with ascites. Eighty percent of ascitic patients had a greater than 15% fall in ERPF after administration of indomethacin compared with 20% of nonascitic patients (P less than 0.025). An infusion of prostaglandin A1 in 13 patients corrected the decrease in ERPF and creatinine clearance that had followed the administration of indomethacin. The administration of indomethacin caused a significant fall in plasma renin activity, 8.2 +/- 2.5 to 3.6 +/- 1.4 ng/ml/hr (P less than 0.025). The fall in plasma renin activity occurred when ERPF was depressed maximally, suggesting that endogenous prostaglandins exert more control over renin release than does ERPF. Prostaglandins appear to be an important factor in maintaining renal blood flow in patients with cirrhosis and sodium retention.
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PMID:Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease. 44 34

To assess the effect of renal prostaglandins on the prognosis of liver cirrhosis, we studied the relationship between the effect of prostaglandin synthetase inhibition by indomethacin on glomerular filtration rate (GFR) and effective renal plasma flow (RPF) and survival in 30 patients with liver cirrhosis. After indomethacin administration, GFR dropped significantly from 86 +/- 2 ml/min to 73 +/- 3 ml/min (p less than 0.01) and RPF from 421 +/- 10 to 349 +/- 14 ml/min (p less than 0.01). Survival was not correlated with baseline GFR or RPF, but was correlated with changes in both GFR and RPF after indomethacin administration (p less than 0.01). The cumulative survival rate from 1 to 7 yr was significantly higher (p less than 0.01) in patients with a decrease in GFR of less than or equal to 15% after indomethacin administration than in patients with a decrease in GFR of more than 15%. Findings for changes in RPF after indomethacin administration were similar. These results suggest that the augmentation of prostaglandin inhibition by indomethacin is associated with a poor prognosis of liver cirrhosis. It may be involved in the depletion of renal prostaglandins to maintain renal hemodynamics in patients with liver cirrhosis.
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PMID:Effect of renal prostaglandins on survival in patients with liver cirrhosis. 291 84

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.
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PMID:Characterization of renal prostaglandin E responsiveness in decompensated cirrhosis: implications for renal sodium handling. 712 24

The paper summarizes the results of in-depth study of the prostaglandin system in healthy individuals and in patients with chronic hepatic diseases. Radioimmunological, gas chromatographic, enzyme immunoassays, and other biochemical studies have first provided evidence for the relationship between the impaired endogenous biological synthesis of prostaglandins (PG) E, F2 alpha, I2, thromboxane A2, the development of metabolic and hormonal disorders and the severity of hepatic failure in chronic hepatitis and cirrhosis of varying etiology, which leads to the conclusion that PGs play an important role in the regulation of liver function and in the pathogenesis of chronic damages. Previously unknown biochemical mechanisms of decreased PGE, PGF2 alpha, and PGI2 in this diseased organ have been revealed, which trigger the deficiency of their precursors (essential fatty acids), the impairment of lipid metabolism and the activity decline of prostaglandin synthetase and adenylate cyclase, etc. A concept on the multiplicity of the biochemical mechanisms responsible for systemic PG action, whose impairments are essential in the pathogenesis of chronic hepatic diseases has been forwarded. The findings are discussed by comparing recent data published in the literature on this problem.
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PMID:[Prostaglandins in chronic liver diseases]. 866