title: The transplanted liver graft is capable of clearing asymmetric dimethylarginine.
abstract: Asymmetric dimethylarginine (ADMA) has been recognized as an endogenous inhibitor of the arginine-nitric oxide (NO) pathway. Its concentration is tightly regulated by urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which is highly expressed in the liver. Considering the liver as a crucial organ in the clearing of ADMA, we hypothesized increased ADMA levels during hepatic failure and, consequently, a decline of ADMA concentrations after successful liver transplantation. The aim of the present study was to investigate the role of the liver in the metabolism of ADMA in patients undergoing liver transplantation. In this prospective study, we investigated the course of ADMA concentrations in 42 patients undergoing liver transplantation and results showed that preoperative ADMA concentrations were higher in patients with acute (1.26 micromol/L, P < .001) and in patients with chronic (.69 micromol/L, P < .001) hepatic failure compared with healthy volunteers (.41 micromol/L). In addition, ADMA concentrations decreased from the preoperative day to the first postoperative day in both the acute (Delta(ADMA): -.63 micromol/L, P = .005) and the chronic hepatic failure group (Delta(ADMA): -0.15 micromol/L, P < .001). Furthermore, in patients who experienced acute rejection, ADMA concentrations were higher during the whole first postoperative month compared with nonrejectors (P = .012). Moreover, in 11 of 13 rejectors (85%) a clear increase in ADMA concentration preceded the onset of the first episode of rejection, which was confirmed by liver biopsy. In conclusion, our results indicate that the transplanted liver graft is quickly capable of clearing ADMA, suggesting preservation of DDAH. In addition, increased ADMA concentrations in the posttransplantation period reflect serious dysfunction of the liver graft during acute rejection.
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. mpc.siroen@vumc.nl <mpc.siroen@vumc.nl>
authors.forename: Michiel P C
authors.initials: MP
authors.lastname: Siroen
authors.forename: Michiel C
authors.initials: MC
authors.lastname: Warlé
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nijveldt
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Kuik
authors.forename: Joost R M
authors.initials: JR
authors.lastname: van der Sijp
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: Ben
authors.initials: B
authors.lastname: van der Hoven
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
mesh_terms: D000208:Acute Disease; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D006084:Graft Rejection / Q000097:blood; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D017093:Liver Failure / Q000097:blood; D016031:Liver Transplantation; D009994:Osmolar Concentration; D011184:Postoperative Period; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine