Gomaa Salwa H, Shamseya Mohammed M, Madkour Marwa A
Departments of Chemical Pathology.
Experimental and Clinical Internal Medicine, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
Eur J Gastroenterol Hepatol. 2019 Jun;31(6):692-702. doi: 10.1097/MEG.0000000000001347.
This study aimed to assess urinary neutrophil gelatinase-associated lipocalin (uNGAL) and serum cystatin C (sCys C) in liver cirrhosis patients with renal dysfunction and to evaluate their role in the diagnosis of the hepatorenal syndrome (HRS).
Forty-five liver cirrhosis patients were enrolled in the study and they were divided into three groups; the first group included 15 patients with normal renal function, the second group included 15 patients with HRS; and the third group included 15 patients with chronic kidney disease (CKD). There was a fourth group, which included 15 healthy controls. Liver and renal function tests, as well as the estimated glomerular filtration rate were determined. uNGAL was measured using the enzyme-linked immunosorbent assay, and the uNGAL/urinary creatinine concentration (UCC) ratio was calculated. sCys C was measured using the particle-enhanced immunoturbidimetric assay.
The ratios of uNGAL and uNGAL/UCC were the highest among HRS patients. The combined uNGAL/UCC ratio and sCys C improved the sensitivity of diagnosis to 93.33% and specificity to 76.67%, with the highest area under the curve of 0.944, 95% confidence interval of 0.879-1.0 (P<0.001). The three biomarkers could successfully identify HRS at the following cutoffs: 84.94 ng/ml, 0.6 ng/mg, and 1.6 mg/l, respectively. Significant positive correlations were found between uNGAL, uNGAL/UCC ratios as well as sCys C and KDIGO stage in liver cirrhosis patients with CKD.
uNGAL and a better uNGAL/UCC ratio can be used alone or together with serum cystatin C as early biomarkers for HRS among patients with decompensated liver cirrhosis. Moreover, uNGAL, uNGAL/UCC as well as serum cystatin C could aid the prognostic assessment of cirrhotic patients with CKD.
本研究旨在评估肾功能不全的肝硬化患者的尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）和血清胱抑素C（sCys C），并评估它们在肝肾综合征（HRS）诊断中的作用。
45例肝硬化患者纳入本研究，分为三组；第一组包括15例肾功能正常的患者，第二组包括15例HRS患者；第三组包括15例慢性肾脏病（CKD）患者。第四组为15名健康对照者。测定肝功能和肾功能指标以及估算肾小球滤过率。采用酶联免疫吸附测定法检测uNGAL，并计算uNGAL/尿肌酐浓度（UCC）比值。采用颗粒增强免疫比浊法检测sCys C。
HRS患者的uNGAL和uNGAL/UCC比值最高。联合uNGAL/UCC比值和sCys C可将诊断敏感性提高至93.33%，特异性提高至76.67%，曲线下面积最高为0.944，95%置信区间为0.879 - 1.0（P<0.001）。这三种生物标志物在以下临界值时可成功识别HRS：分别为84.94 ng/ml、0.6 ng/mg和1.6 mg/l。在患有CKD的肝硬化患者中，uNGAL、uNGAL/UCC比值以及sCys C与KDIGO分期之间存在显著正相关。
uNGAL和更佳的uNGAL/UCC比值可单独使用，或与血清胱抑素C一起作为失代偿期肝硬化患者HRS的早期生物标志物。此外，uNGAL、uNGAL/UCC以及血清胱抑素C有助于对患有CKD的肝硬化患者进行预后评估。
