misoprostol and Ascites

Non-steroidal anti-inflammatory drugs (NSAIDs) often cause renal dysfunction in cirrhotic patients with ascites through inhibition of prostaglandin synthesis. However, their renal effects in cirrhotic patients without ascites are controversial. In addition, the role of prostaglandins in cirrhotic patients with ascites and in non-ascitic cirrhotic patients receiving NSAIDs also remains elusive. Thus we evaluated the chronic renal effects of indomethacin and misoprostol in 9 cirrhotic patients with ascites (protocol 1) and 21 cirrhotic patients without ascites (protocol 2).. The patients of protocol 1 received 200 micrograms of misoprostol every 6 h for 7 consecutive days. In protocol 2, 11 patients received 25 mg indomethacin three times a day for 7 consecutive days. The other 10 patients received 25 mg indomethacin three times a day plus 200 micrograms misoprostol every 6 h for 7 consecutive days. Renal function tests, plasma renin activity, and plasma aldosterone concentration were measured before and after treatment.. In protocol 1, misoprostol tended to reduce the urinary sodium excretion (p = 0.08). In protocol 2, indomethacin alone greatly impaired renal plasma flow (p < 0.05), creatinine clearance (p < 0.05), blood urea nitrogen (p < 0.05), and serum creatinine (p = 0.06) in 11 patients. Similar magnitudes of renal dysfunction were observed in the other 10 patients despite the concomitant misoprostol treatment.. Chronic administration of misoprostol may have caused a negative natriuretic effect in cirrhotic patients with ascites. In cirrhotic patients without ascites chronic administration of indomethacin may induce a renal dysfunction that cannot be reversed by misoprostol.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Ascites; Drug Therapy, Combination; Female; Humans; Indomethacin; Kidney; Kidney Function Tests; Liver Cirrhosis; Male; Middle Aged; Misoprostol; Time Factors

Prostaglandins play an important role in the maintenance of renal hemodynamics and water excretion in cirrhosis. To investigate whether the administration of prostaglandins improves renal function in cirrhotic patients with ascites, 16 patients with functional renal failure and/or dilutional hyponatremia were given oral misoprostol, a prostaglandin E1 analogue (200 micrograms/6 h for 4 days; n = 9) or intravenous prostaglandin E2 (0.5 microgram/min for 1 h followed by 1 microgram/min for another hour; n = 7). The administration of misoprostol did not induce significant changes in the glomerular filtration rate (59 +/- 11 vs. 54 +/- 11 ml/min), sodium excretion (4.0 +/- 1.3 vs. 4.1 +/- 2.1 microEq/min), and free water clearance (2.4 +/- 0.8 vs. 2.1 +/- 0.9 ml/min), nor did it improve the natriuretic response to an intravenous bolus of 40 mg of furosemide (486 +/- 124 vs. 406 +/- 88 microEq/min). Similarly, an infusion of prostaglandin E2 did not induce significant changes in the glomerular filtration rate (baseline: 33 +/- 6; 0.5 microgram/min: 31 +/- 5; 1 microgram/min: 31 +/- 6 ml/min) and sodium excretion (5.7 +/- 2.7; 3.2 +/- 1.4; and 1.5 +/- 0.7 microEq/min, respectively), whereas free water clearance decreased significantly (1.1 +/- 0.7; 0.5 +/- 0.5; and -0.1 +/- 0.2 ml/min, respectively, p < 0.05). These results indicate that oral misoprostol or the intravenous infusion of prostaglandin E2 do not improve renal function in cirrhosis with ascites.

Topics: Administration, Oral; Adult; Aged; Ascites; Dinoprostone; Diuresis; Female; Glomerular Filtration Rate; Humans; Hyponatremia; Infusions, Intravenous; Kidney; Liver Cirrhosis; Male; Middle Aged; Misoprostol; Natriuresis; Renal Circulation; Renal Insufficiency