Elevation of asymmetric dimethylarginine (ADMA) in patients developing hepatic failure after major hepatectomy.
BACKGROUND
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the arginine-nitric oxide pathway. It is conceivable that its concentration is tightly regulated by urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver. In rats, we showed a high net hepatic uptake of ADMA. Therefore, we aimed to confirm the role of the liver in humans and hypothesized elevated ADMA levels after major liver resection by a reduction of functional liver mass and injury to the remnant liver.


METHODS
Patients undergoing a major hepatic resection (HEP, n = 17) or major abdominal surgery (MAS, n = 12) were included and followed in time. In addition, ADMA levels were measured in 4 patients having severe hepatic failure after a liver resection. Plasma ADMA concentration was measured by high-performance liquid chromatography.


RESULTS
Preoperatively and on days 1, 3, and 5, plasma levels of ADMA were higher in HEP patients when compared with MAS patients. In HEP patients with prolonged (>7 days) hepatic injury, ADMA levels were especially elevated. On the first postoperative day, ADMA significantly correlated to bilirubin concentration (r = .528, p < .05) as a marker of postoperative hepatic function. Besides, in patients with severe hepatic failure, ADMA levels were highly elevated.


CONCLUSIONS
In the present study, evidence was found for the role of the liver in the elimination of ADMA in humans. Increased levels of ADMA occur in the postoperative course after a major hepatic resection, especially when liver function is severely impaired. Further studies need to assess the role of ADMA in the development of complications after liver surgery.
Nijveldt
Robert J
RJ
Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. rj.nijveldt@vumc.nl
Teerlink
Tom
T
Siroen
Michiel P C
MP
van der Hoven
Ben
B
Prins
Hubert A
HA
Wiezer
Marinus J
MJ
Meijer
Catharina
C
van der Sijp
Joost R M
JR
Cuesta
Miguel A
MA
Meijer
Sybren
S
van Leeuwen
Paul A M
PA
D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001663:Bilirubin / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008099:Liver / Q000201:enzymology*; D017093:Liver Failure / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period
C487735:dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase; D001663:Bilirubin