ACLF相关AKI患者的血清集聚蛋白多糖C端片段水平及其诊断价值

摘要/Abstract

摘要： 目的探讨并发急性肾损伤(acute kidney injury,AKI)的慢加急性肝功能衰竭(acute-chronic liver failure,ACLF)患者血清集聚蛋白多糖C端片段(C-terminal agrin fragment,CAF)水平用于AKI诊断的价值。方法 HBV相关ACLF患者347例,其中AKI患者165例,无AKI患者182例。记录患者一般信息及常规实验室指标,检测血清CAF水平。分析CAF与各项指标的相关性,ROC曲线分析CAF用于ACLF患者AKI诊断的效能。结果 AKI组CAF水平[1243.3(678.4,2105.9) pg/mL]显著高于无-AKI组[250.2(135.7,436.5) pg/mL],差异有统计学意义(P<0.01);不同AKI分期CAF水平由高至低依次为:AKI-3期＞AKI-2期＞AKI-1期。AKI组患者血清CAF水平与MAP呈显著负相关(R=-0.242,P=0.004)、eGFR(R=-0.480,P<0.01),与ALT(R=0.222,P=0.004)、WBC(R=0.212,P=0.006)、sCr(R=0.392,P<0.01)及MELD评分(R=0.272,P<0.01)。CAF用于诊断ACLF并发AKI的AUC为0.859(95%CI:0.819～0.898),而CAF联合sCr的AUC为0.923(95%CI:0.894～0.951)。结论 CAF反映ACLF患者并发AKI时的肾功能损害严重程度,并可与sCr联合用于提高AKI的诊断效能。

关键词: 慢加急性肝衰竭, 急性肾损伤, 集聚蛋白多糖C端片段, 诊断

Abstract: Objective To investigate serum C-terminal agrin fragment (CAF) level and its clinical diagnostic value in acute kidney injury (AKI) patients with acute-on-chronic liver failure (ACLF).Methods A total of 347 patients with hepatitis B virus (HBV) related ACLF from April 2012 to February 2015 in our center were enrolled retrospectively, and then divided into AKI group (n=165) and non-AKI group (n=182). The general information and routine laboratory parameters were recorded, and the serum CAF level was detected. The correlation between CAF and parameters was analyzed, and diagnostic efficiency of CAF for AKI in patients with ACLF was evaluated by receiver operating characteristic (ROC) curve. Results The level of CAF in AKI group (1243.3(678.4-436.5) pg/mL) was significantly higher than that in non-AKI group (250.2 (2105.9 ~ 135.7) pg/mL, P<0.001), and increased with different stage of AKI, in order from AKI-1 to AKI-2 to AKI-3. In addition, the CAF levels were significantly negatively correlated with mean arterial pressure (MAP) (R=-0.242, P=0.004) and glomerular filtration rate (R=-0.480, P<0.001), while positively correlated with alanine aminotransferase level (R=0.222, P=0.004), white blood cell count (R=0.212, P=0.006), serum creatinine (sCr) level (R=0.272, P<0.001) and model for end stage liver disease score (R=0.392, P<0.001). Area under the curve (AUC) of CAF used for the diagnosis of AKI in patients with ACLF was 0.859 (95%CI: 0.819-0.898), and the AUC of CAF with sCr was 0.923 (95%CI: 0.894-0.951).Conclusion CAF can reflect the severity of renal damage of AKI in patients with ACLF, and it can be combined with sCr to improve the diagnosis efficiency of AKI.

Key words: Acute-on-chronic liver failure, Acute kidney injury, C-terminal agrin fragment, Diagnosis

游国琼, 王丽, 段萌. ACLF相关AKI患者的血清集聚蛋白多糖C端片段水平及其诊断价值[J]. 肝脏, 2016, 21(4): 248-252.

YOU Guo-qiong, WANG Li, DUAN Meng. Serum C-terminal agrin fragment level in AKI patients with ACLF and its clinical diagnostic value[J]. Chinese Hepatolgy, 2016, 21(4): 248-252.

参考文献

[1] Bernal W, Jalan R, Quaglia A, et al. Acute-on-chronic liver failure. Lancet, 2015, 386:1576-1587.
[2] Angeli P, Rodriguez E, Piano S, et al. Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis. Gut, 2015, 64:1616-1622.
[3] Moore JK, Love E, Craig DG, et al. Acute kidney injury in acute liver failure: a review. Expert Rev Gastroenterol Hepatol, 2013, 7:701-712.
[4] Garsen M, Rops AL, Rabelink TJ, et al. The role of heparanase and the endothelial glycocalyx in the development of proteinuria. Nephrol Dial Transplant, 2014, 29:49-55.
[5] Steubl D, Hettwer S, Dahinden P, et al. C-terminal agrin fragment (CAF) as a serum biomarker for residual renal function in peritoneal dialysis patients. Int Urol Nephrol, 2015, 47:391-396.
[6] Sarin SK, Kedarisetty CK, Abbas Z, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int, 2014, 8:453-471.
[7] Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis, 2013, 61:649-672.
[8] European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol, 2010, 53:397-417.
[9] Kamath PS, Kim WR, Advanced Liver Disease Study G. The model for end-stage liver disease (MELD). Hepatology, 2007, 45:797-805.
[10] Belcher JM, Parikh CR, Garcia-Tsao G. Acute kidney injury in patients with cirrhosis: perils and promise. Clin Gastroenterol Hepatol, 2013, 11:1550-1558.
[11] Zarjou A, Agarwal A. Sepsis and acute kidney injury. J Am Soc Nephrol, 2011, 22:999-1006.
[12] Mayeux PR, MacMillan-Crow LA. Pharmacological targets in the renal peritubular microenvironment: implications for therapy for sepsis-induced acute kidney injury. Pharmacol Ther, 2012, 134:139-155.
[13] Brochard L, Abroug F, Brenner M, et al. An official ATS/ERS/ESICM/SCCM/SRLF statement: prevention and management of acute renal failure in the ICU patient: an international consensus conference in intensive care medicine. Am J Respir Crit Care Med, 2010, 181:1128-1155.
[14] Cordoba J, Ventura-Cots M, Simon-Talero M, et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol, 2014, 60:275-281.
[15] Drey M, Behnes M, Kob R, et al. C-terminal agrin fragment (CAF) reflects renal function in patients suffering from severe sepsis or septic shock. Clin Lab, 2015, 61:69-76.
[16] Steubl D, Hettwer S, Vrijbloed W, et al. C-terminal agrin fragment-a new fast biomarker for kidney function in renal transplant recipients. Am J Nephrol, 2013, 38:501-508.