Transjugular intrahepatic portosystemic shunt-placement increases arginine/asymmetric dimethylarginine ratio in cirrhotic patients

Abstract

AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt (TIPS). METHODS: To determine arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and nitric oxide (NO) plasma levels, blood samples were collected from the superior cava, hepatic, and portal vein just before, directly after, and 3 mo after TIPS-placement. RESULTS: A significant increase in the arginine/ADMA ratio after TIPS placement was shown. Moreover, TIPS placement enhanced renal function and thereby decreased systemic SDMA levels. In patients with renal dysfunction before TIPS placement, both the arginine/ ADMA ratio and creatinine clearance rate increased significantly, while this was not the case in patients with normal renal function before TIPS placement. Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured. CONCLUSION:The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability. In addition, this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase (DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.

Asymmetric dimethylarginine is strongly associated with cognitive dysfunction and brain MR spectroscopic abnormalities in cirrhosis

“…Similar to prior published experience, there was no significant change in ADMA levels after TIPS placement in the entire group[21]. We also did not find a difference in the baseline ADMA levels between those who did or did not develop HE ultimately.…”

The dimethylarginine (ADMA)/nitric oxide pathway in the brain and periphery of rats with thioacetamide-induced acute liver failure: Modulation by histidine

“…Several studies have shown that ADMA levels are increased in plasma of patients with severe acute alcoholic hepatitis and ALF (Mookerjee et al, 2007a(Mookerjee et al, , 2007b. Recent evidence indicates that the l-arginine/ ADMA ratio in plasma is increased in cirrhotic patients with transjugular intrahepatic portosystemic shunt (TIPS) (Bajaj et al, 2013;Siroen et al, 2008), which implicates an increase in intracellular NO bioavailability. Moreover, higher ADMA concentration is related to worsened outcome of cognition tests in TIPS patients and predict the transition from asymptomatic to overt HE (Bajaj et al, 2013).…”

Estimation of Glomerular Filtration Rate in Patients With Cirrhosis by Using New and Conventional Filtration Markers and Dimethylarginines

“…Siroen et al . 17 demonstrated a significant negative correlation between SDMA levels and creatinine clearance in patients with alcoholic cirrhosis undergoing transjugular intrahepatic porto-systemic shunt placement (P<0.001). Lluch et al .…”

“…20 showed that (SDMA+ADMA) was significantly elevated in patients with acute alcoholic hepatitis plus cirrhosis compared to those who had cirrhosis alone. The results of these two studies in subjects with cirrhosis suggested that dimethylarginines might be a useful GFR marker in cirrhosis 17–20 .…”