The effects of chronic administration of indomethacin and misoprostol on renal function in cirrhotic patients with and without ascites.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hsia
H C
HC
Dept. of Medicine, National Yang-Ming University, Taipei, Taiwan.
Lin
H C
HC
Tsai
Y T
YT
Lee
F Y
FY
Hwang
C C
CC
Hou
M C
MC
Lee
S D
SD
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001201:Ascites / Q000209:etiology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000009:adverse effects*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016595:Misoprostol; D007213:Indomethacin