尿肾损伤分子-1对药物肾毒性诊断性能的研究

目的 在庆大霉素诱导大鼠急性肾损伤模型中评价尿肾损伤分子-1(Kim-1)作为肾毒性生物标志物的诊断性能。方法 ip 60和120 mg/kg庆大霉素,每天给药1次,连续10 d,制备大鼠急性肾损伤模型。在给药第2、4、8、11天,进行肾脏组织病理分析,检测尿液Kim-1、血清尿素氮(BUN)和肌酐(Cr)水平。结果 病理学结果显示,庆大霉素组大鼠出现典型肾损伤变化,呈明显的剂量及时间相关性;与对照组比较,庆大霉素低、高剂量组尿液Kim-1浓度在给药第4天即开始出现显著升高(P<0.05),增幅程度明显高于传统指标BUN和Cr,并且呈显著剂量和时间相关性;受试者操作特性曲线(ROC)结果表明,尿Kim-1的曲线下面积(AUC)明显优于BUN和Cr。结论 尿Kim-1的肾毒性诊断性能优于传统肾功能评价指标,可作为一种药物肾毒性的候选生物标志物。

Urinary biomarker Kim-1 analysis on drug-induced renal injury model

Objective To evaluate the performance of Kim-1 as nephrotoxicity biomarker on rat acute kidney injury induced by gentamicin. Methods A rat model of acute kidney injury was developed by daily ip injection of 60 or 120 mg/kg gentamicin for consecutive 10 d. The histopathological analysis of kidneys was performed. The level of Kim-1 in urine, BUN and Cr in serum from different time points were determined. Results Histopathological analysis demonstrated that traditional renal injury findings were found in gentamicin-treated animals. The number of animals with tubular cell necrosis injury appeared to increase and the severity of renal damage had been aggravated over time. Urinary biomarker analysis showed that urine Kim-1 began to increase largely in animal from low- and high-dose groups since day 4, which were higher than BUN and Cr. Obvious time- and dose-response were found. ROC analysis also demonstrated that AUCs of Kim-1 was superior to BUN and Cr. Conclusion Performance of Kim-1 is better than traditional renal function markers, suggesting that it could be served as a candidate biomarker for detection of drug-induced nephrotoxicity.