Wnuk Zuzanna, Kokot Franciszek, Kunsdorf-Wnuk Anna
St. Barbara's Hospital, Sosnowiec, Poland.
Pol Arch Med Wewn. 2012;122(7-8):367-73. doi: 10.20452/pamw.1355. Epub 2012 Jun 11.
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.
一氧化氮是肝硬化发病机制中的一个重要因素。其合成取决于L-精氨酸的可用性,并受到不对称二甲基精氨酸(ADMA)的抑制。对称二甲基精氨酸(SDMA)似乎是多器官功能衰竭尤其是肾衰竭的一个良好标志物。
本研究的目的是评估二甲基精氨酸在肝移植患者中的诊断意义。
该研究纳入了30例尸体肝脏供体和30例肝硬化受体。在供体以及肝受体移植前、移植后第1天和第3天评估以下参数:血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和γ-谷氨酰转肽酶(GGT)活性、国际标准化比值(INR)、胆红素、白蛋白、肌酐、电解质、ADMA、SDMA和L-精氨酸的浓度。
与供体相比,移植前肝硬化患者的胆红素浓度更高、ALT和GGT活性更高,而钠和白蛋白水平更低。移植后第3天,我们观察到ALT、AST、肌酐、钠、ADMA、SDMA和L-精氨酸显著升高,胆红素水平降低。在供体(P<0.001)、移植前受体(P<0.0005)以及移植后第1天(P<0.004)和第2天(P<0.0005),发现SDMA与肌酐之间存在显著正相关。在移植前ADMA与胆红素浓度之间(P = 0.0264)、移植后第1天ADMA与白蛋白浓度之间(P = 0.02)也观察到显著正相关,而在受体移植前(P = 0.008)和移植后第3天(P = 0.03),ADMA与INR之间观察到负相关。
肝移植后二甲基精氨酸水平升高似乎不仅归因于移植肝脏的功能障碍,还归因于手术本身和/或使用肾毒性钙调神经磷酸酶抑制剂——他克莫司导致的肾功能损害。肝供体和受体中血清肌酐与SDMA浓度之间的显著相关性表明,SDMA肾清除率可能对评估这些患者的肾小球滤过率具有诊断价值。