Diagnostic value of plasma asymmetric and symmetric dimethylarginine levels in liver transplant recipients

Abstract

Nitric oxide is an important factor in the pathogenesis of liver cirrhosis. Its synthesis depends on the availability of L‑arginine and is inhibited by asymmetric dimethylarginine (ADMA). Symmetric dimethylarginine (SDMA) seems to be a good marker of multiorgan failure, especially renal failure. The aim of the present study was to evaluate the diagnostic significance of dimethylarginines in patients after liver transplantation. The study included 30 cadaver liver donors and 30 recipients with liver cirrhosis. The following parameters were estimated in donors and in liver recipients before and at days 1 and 3 after transplantation: serum alanine transaminase (ALT), aspartate transaminase (AST), and γ‑glutamyltranspeptidase (GGT) activity, international normalized ratio (INR), concentrations of bilirubin, albumin, creatinine, electrolytes, ADMA, SDMA, and L‑arginine. Before transplantation cirrhotic patients showed higher bilirubin concentrations, higher ALT and GGT activity, and lower sodium and albumin levels compared with donors. At day 3 after transplantation, we observed a significant increase in ALT, AST, creatinine, sodium, ADMA, SDMA, and L‑arginine, and a decrease in bilirubin levels. A significant positive correlation between SDMA and creatinine was found in donors (P <0.001), recipients before transplantation (P <0.0005), and at days 1 (P <0.004) and 2 after transplantation (P <0.0005). A significant positive correlation was also observed before transplantation between ADMA and bilirubin concentrations (P = 0.0264), ADMA and albumin concentrations at day 1 after transplantation (P = 0.02), while a negative correlation was observed between ADMA and INR before transplantation (P = 0.008) and at day 3 after transplantation (P = 0.03) in recipients. An increase in dimethylarginine levels after liver transplantation seems to be due not only to the dysfunction of the transplanted liver, but also to impaired kidney function caused by the surgery itself and/or the use of a nephrotoxic calcineurin inhibitor--tacrolimus. A significant correlation between serum creatinine and SDMA concentrations both in liver donors and recipients suggests that SDMA renal clearance may have diagnostic value to evaluate the glomerular filtration rate in these patients.