Nephrology Section, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Investig Med. 2013 Mar;61(3):564-8. doi: 10.2310/JIM.0b013e31828233a8.
Several biomarkers are becoming available for the early detection of acute kidney injury (AKI), but few have been directly compared.
To compare urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl glucosaminidase (NAG) against serum creatinine and renal histological score in the initiation, maintenance, and recovery phases of cisplatin (CP)-induced AKI.
Sprague-Dawley rats (300-350 g) were injected once through their tail veins with CP (CP group) at 5.5 mg/kg or with same volume of normal saline vehicle (Control group). Rats were euthanized at 2, 4, 6, 12, and 24 hours, and on days 2, 3, 6, and 10 (n = 12 in the CP group and n = 6 in the Control group at each time point), and urine, blood, and kidney samples were analyzed.
A significant increase in serum creatinine was noted by day 3 in the CP group versus Control group [1.46 (0.12) vs 0.28 (0.03) mg/dL; mean (SE); P < 0.05]. The renal histology scores for brush border loss and tubular necrosis were significantly higher at 12 and 24 hours, respectively, in the CP group. Urinary kidney injury molecule-1 levels were significantly higher at 24 hours in the CP group than in the Control group [48.26 (13.13) vs 8.21 (3.31) pg/mg creatinine; P < 0.05] and remained elevated through day 10. Both urine NAG and NGAL levels were significantly higher by day 2 in the CP than in the Control group [NAG, 8.19 (0.82) vs 3.48 (0.40) pg/mg creatinine, P G 0.05; NGAL, 2911.80 (368.10) vs 1412.60 (250.20) pg/mg creatinine, P < 0.05]. Urinary NAG remained elevated for 6 days and NGAL for 3 days.
Our study suggests a temporal hierarchy in the ability of certain urinary protein-based biomarkers to detect AKI after a well-defined tubular injury. Comparative analyses of urinary biomarkers are warranted in clinical settings such as patients receiving CP to discern the time course and pattern of expression.
目前已有多种生物标志物可用于急性肾损伤（AKI）的早期检测，但很少有研究直接对这些标志物进行比较。
本研究旨在比较顺铂（CP）诱导 AKI 起始、维持和恢复阶段尿液肾损伤分子 1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和 N-乙酰氨基葡萄糖苷酶（NAG）与血清肌酐和肾组织学评分的相关性。
300-350 g 的 Sprague-Dawley 大鼠经尾静脉单次注射 CP（CP 组，5.5 mg/kg）或等体积生理盐水（对照组）。大鼠分别于 2、4、6、12 和 24 小时以及第 2、3、6 和 10 天（CP 组各时间点 n = 12，对照组 n = 6）安乐死，分析尿液、血液和肾脏样本。
CP 组大鼠血清肌酐在第 3 天明显高于对照组[1.46（0.12）比 0.28（0.03）mg/dL；均数（SE）；P < 0.05]。CP 组大鼠在 12 和 24 小时时肾小管刷状缘丢失和肾小管坏死的肾组织学评分明显更高。CP 组大鼠在 24 小时时尿液 KIM-1 水平明显高于对照组[48.26（13.13）比 8.21（3.31）pg/mg 肌酐；P < 0.05]，且在第 10 天仍持续升高。CP 组大鼠在第 2 天的尿液 NAG 和 NGAL 水平均明显高于对照组[NAG，8.19（0.82）比 3.48（0.40）pg/mg 肌酐，P G 0.05；NGAL，2911.80（368.10）比 1412.60（250.20）pg/mg 肌酐，P < 0.05]。尿液 NAG 升高持续 6 天，尿液 NGAL 升高持续 3 天。
本研究提示在检测特定的肾小管损伤后 AKI 方面，某些基于尿液蛋白的生物标志物的检测能力存在时间上的差异。在 CP 治疗患者等临床环境中，有必要对尿液生物标志物进行比较分析，以辨别其表达的时间过程和模式。
