Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
Pediatr Res. 2013 May;73(5):585-91. doi: 10.1038/pr.2013.34. Epub 2013 Feb 14.
Aminoglycoside exposure is a common cause of acute kidney injury (AKI). Delay in the diagnosis of AKI using conventional biomarkers has been one of the important obstacles in applying early effective interventions. We tested the hypothesis that urinary metabolomics could identify novel early biomarkers for toxic renal injury.
Three-day-old rats were divided into three groups; they received a single daily injection of vehicle (0.9% NaCl solution) or gentamicin at a dose of 10 or 20 mg/kg/d for 7 d. Urine and blood were collected after 3 and 7 d of injections. Urinary metabolites were evaluated using high-performance liquid chromatography and gas chromatography/mass spectrometry.
A distinct urinary metabolic profile characterized by glucosuria, phosphaturia, and aminoaciduria was identified preceding changes in serum creatinine. At both the gentamicin doses, urinary tryptophan was significantly (P < 0.05) increased (fold change: 1.91 and 2.31 after 3 d; 1.81 and 1.93 after 7 d). Similarly, kynurenic acid, a tryptophan metabolite, showed a significant (P < 0.05) decrease (fold change: 0.26 and 0.24 after 3 d; 0.21 and 0.52 after 7 d), suggesting an interruption of the normal tryptophan metabolism pathway.
We conclude that urinary metabolomic profiling provides a robust approach for identifying early and novel markers of gentamicin-induced AKI.
氨基糖苷类药物暴露是急性肾损伤（AKI）的常见原因。使用传统生物标志物诊断 AKI 的延迟是应用早期有效干预措施的重要障碍之一。我们检验了这样一个假设，即尿代谢组学可以识别出毒性肾损伤的新型早期生物标志物。
将 3 日龄大鼠分为 3 组；它们分别接受每日单次注射载体（0.9%生理盐水溶液）或庆大霉素 10 或 20mg/kg/d，连续 7d。在注射后 3d 和 7d 采集尿液和血液。使用高效液相色谱法和气相色谱/质谱法评估尿液代谢物。
在血清肌酐发生变化之前，确定了一种以糖尿、磷尿和氨基酸尿为特征的明显的尿代谢特征。在两种庆大霉素剂量下，尿色氨酸均显著增加（3d 后增加 1.91 和 2.31；7d 后增加 1.81 和 1.93）。同样，色氨酸代谢产物犬尿氨酸也显著降低（3d 后降低 0.26 和 0.24；7d 后降低 0.21 和 0.52），提示正常色氨酸代谢途径中断。
我们的结论是，尿代谢组学分析为鉴定庆大霉素诱导的 AKI 的早期和新型标志物提供了一种强有力的方法。
