检验医学 ›› 2013, Vol. 28 ›› Issue (5): 374-378.DOI: 10.3969/j.issn.1673-8640.2013.05.007

• 临床应用研究.论著 • 上一篇    下一篇

尿NGAL在顺铂化疗肿瘤患者肾小管损伤中的临床意义探讨

胡雷光   

  1. 1.复旦大学附属华山医院静安分院检验科,上海 200040;2.复旦大学附属华山医院静安分院肿瘤科,上海 200040
  • 收稿日期:2012-12-31 修回日期:2013-03-09 出版日期:2013-05-15 发布日期:2013-05-14
  • 作者简介:胡雷光,男,1963年生,学士,副主任技师,主要从事临床检验和实验室管理工作。
  • 基金资助:

    上海市卫生局课题基金资助项目(2010065)

Clinical significance of urinary NGAL determination in tumor patients with renal tubular injury by cisplatin chemotherapy

  1. 1.Department of Clinical Laboratory, Jing′an Branch of Huashan Hospital,Fudan University,Shanghai 200040,China; 2.Department of Oncology, Jing′an Branch of Huashan Hospital,Fudan University,Shanghai 200040,China
  • Received:2012-12-31 Revised:2013-03-09 Online:2013-05-15 Published:2013-05-14

摘要: 目的 探讨尿中性粒细胞明胶酶相关载脂蛋白(NGAL)检测在肿瘤化疗患者肾小管损伤的临床应用价值。 方法 选择58例接受顺铂(DDP)化疗的住院肿瘤患者(包括肺癌、乳腺癌、宫颈癌和腮腺癌等),收集其DDP化疗前24 h和/或DDP化疗后24 h的随机尿标本。化疗前收集57份样本并根据是否初次入院接受化疗分为已化疗组(32份)和未化疗组(25份);化疗后收集54份标本,其中53份与化疗前的标本相配对。另选取51名体检正常者作为对照组。分别检测所有对象尿NGAL、N-乙酰-β-D氨基葡萄糖苷酶(NAG)、α1-微球蛋白(α1-MG)、微量白蛋白(mAlb)和肌酐(Cr)含量,测定结果以尿Cr(UCr)进行校正(即计算前4项指标与UCr的比值)。以NAG阳性作为肾小管损伤的判断指标,将全部观察对象分为有损伤和无损伤2组,运用受试者工作特征曲线(ROC)评价尿NGAL/UCr对肾小管损伤判断的准确性。 结果 化疗前各组结果比较,除未化疗组NGAL/UCr和NAG/UCr高于对照组(P<0.05)外,已化疗组、未化疗组和对照组的其余项目之间差异均无统计学意义(P>0.05)。化疗前组NGAL/UCr、NAG/UCr、α1-MG/UCr[中位数(25%~75%)]分别为1.37(0.76~2.16)mg/mmol、1.30(0.76~2.56)U/mmol、0.21(0.04~0.74)mg/mmol,明显低于化疗后组[2.14(1.39~4.08) mg/mmol、2.58(1.75~4.02)U/mmol、1.00(0.30~1.91)mg/mmol](P<0.01),而mAlb/UCr化疗前、后差异无统计学意义(P>0.05)。化疗前组NGAL/UCr异常率与NAG/UCr、α1-MG/UCr及3项指标联合检测的异常率比较差异均无统计学意义(P>0.05);化疗后组NGAL/UCr和3项指标联合检测的异常率明显高于NAG/UCr、α1-MG/UCr(P<0.05)。NGAL/UCr的ROC曲线下面积(AUC)为0.770 1[95%可信区间:0.698 4~0.841 7],诊断切割点为1.15 mg/mol(灵敏度为82.09%,特异性为61.05%)。 结论 尿NGAL/UCr对DDP化疗患者肾小管损伤和功能减退的检出有一定的临床应用价值。对于药物性等肾毒性损伤,尿NGAL可以作为一种较为理想的生物标志物。

关键词: 中性粒细胞明胶酶相关载脂蛋白, 顺铂, 化疗, 肿瘤, 肾小管损伤

Abstract: Objective To investigate the application significance of urinary neutrophil gelatinase-associated lipocalin (NGAL) determination in tumor patients with renal tubular injury by chemotherapy. Methods The random urine specimens were collected within 24 h before and after cisplatin(DDP) chemotherapy in 58 tumor inpatients (including lung, breast, cervical, parotid gland cancers and so on) who were treated by DDP chemotherapy. There were 57 urine specimens that were collected from patients before chemotherapy. They were classified into 2 groups, 25 specimens for the patients without chemotherapy and 32 specimens for the patients with once chemotherapy at least before admission. A total of 53 of 54 urine specimens after chemotherapy paired with ones before chemotherapy. A total of 51 healthy subjects were enrolled as control group. The levels of urinary NGAL, N-acetyl-beta-D-amino glucosidase (NAG), alpha1-microglobulin (α1-MG), urinary microalbumin (mAlb) and urinary creatinine (Cr) were determined. According to urinary Cr(UCr), the 4 indicators were corrected by calculating for NGAL/UCr, NAG/UCr, α1-MG/UCr and mAlb/UCr ratio. According to the NAG positive as renal tubular injury judgment index,the all objectives were classified into 2 groups of injury and non-injury. The accuracy of renal tubular injury judged by urinary NGAL/UCr was assessed by the receiver operating characteristic (ROC)curve.  Results Comparing the results of patients with chemotherapy, patients without chemotherapy before admission and controls, there was no statistical significance (P>0.05), except NGAL/UCr and NAG/UCr of patients without chemotherapy were higher than those of controls (P<0.05). Of the results between patients before chemotherapy and after chemotherapy, when the median was 25%-75%, NGAL/UCr were 1.37(0.76-2.16)mg/mmol and 2.14(1.39- 4.08)mg/mmol, NAG/UCr were 1.30(0.76-2.56) U/mmol and 2.58(1.75-4.02)U/mmol,and α1-MG/UCr were 0.21(0.04-0.74)mg/mmol and 1.00(0.30-1.91)mg/mmol(P<0.01). The difference of mAlb/UCr was no statistically significant before and after chemotherapy(P>0.05). Comparing NGAL/UCr abnormality with NAG/UCr, α1-MG/UCr and the combined result abnormalities of the 3 indicators, the differences of their abnormalities in patients before chemotherapy were not statistically significant (P>0.05). The NGAL/UCr abnormality and the combined result abnormalities of the 3 indicators were higher than those of NAG/UCr and α1-MG/UCr in patients after chemotherapy (P<0.05). The area under the ROC curve (AUC) of NGAL/UCr was 0.770 1, its 95% confidence interval was 0.698 4-0.841 7. The diagnosis cut-off value was 1.15 mg/mol (the sensitivity was 82.09%, and the specificity was 61.05%).  Conclusions Urinary NGAL/UCr have clinical application significance in patients with renal tubular injury and kidney function decline by DDP chemotherapy. To prevent from drug nephrotoxic injury, urinary NGAL determination may become a kind of novel selectable biological marker.

Key words: Neutrophil gelatinase-associated lipocalin, Cisplatin, Chemotherapy, Tumor, Renal tubular injury