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

doi:10.3969/j.issn.1673-8640.2013.05.007

Abstract

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

HU Leiguang 1，ZHU Liyue 1，XIE Fang 2，CHEN Jian 1，WANG Xinlei 1. Clinical significance of urinary NGAL determination in tumor patients with renal tubular injury by cisplatin chemotherapy[J]. , 2013, 28(5): 374-378.

References

[1]须静，胡晓波. 中性粒细胞明胶酶相关脂质运载蛋白的研究进展[J]. 检验医学，2012，27(10)：871-876.
[2]Mishra J，Ma Q，Prada A，et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury[J]. J Am Soc Nephrol，2003，14(10)：2534-2543.
[3]Schmidt-Ott KM，Mori K，Li JY，et al. Dual action of neutrophil gelatinase-associated lipocalin[J]. J Am Soc Nephrol，2007，18(2)：407-413.
[4]蔡雷鸣，厉倩，金才峰，等. 血清中性粒细胞明胶酶相关脂质运载蛋白检测在急性肾功能损伤早期诊断中的临床意义[J]. 检验医学，2012，27(4)：287-290.
[5]Ma Q，Devarajan P. Induction of proapoptotic Daxx following ischemic acute kidney injury[J]. Kidney Int，2008，74(3)：310-318.
[6]Srichai MB，Hao C，Davis L，et al. Apoptosis of the thick ascending limb results in acute kidney injury[J]. J Am Soc Nephrol，2008，19(8)：1538-1546.
[7]Haase M，Devarajan P，Haase-Fielitz A，et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury： a multicenter pooled analysis of prospective studies[J]. J Am Coll Cardiol，2011，57（17）：1752-1761.
[8]Ramesh G，Reeves WB. Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha[J]. Kidney Int，2004，65(2)：490-499.
[9]Mishra J， Mori K， Ma Q，et al. Neutrophil gelatinase-associated lipocalin： a novel early urinary biomarker for cisplatin nephrotoxicity[J]. Am J Nephrol，2004，23（3）：307-315.
[10]Devireddy LR， Gazin C， Zhu X，et al. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake[J]. Cell，2005，123（7）：1293-1305.
[11]托马斯.临床实验诊断学[M].上海：上海科技出版社，2004：357-375.
[12]梁永正，史伟，刘双信，等．肾小管功能检测在IgA肾病中的意义[J]．广东医学，2004，25(2)：185-186．
[13]Gonzales-Vitale JC， Hayes DM， Cvitkovic E，et al . The renal pathology in clinical trials of cis-platinum(Ⅱ) diamminedichloride[J]. Cancer，1997，39（4）：1362-1371.
[14]曾健，劳山.顺铂肾毒性机制及其防护的研究进展[J]. 中国实用医药，2008，3(10)：194-195.
[15]Gaspari F， Cravedi P， Mandalà M，et al. Predicting cisplatin-induced acute kidney injury by urinary neutrophil gelatinase-associated lipocalin excretion： a pilot prospective case-control study[J]. Nephron Clin Pract，2010，115（2）：c154-c160.