Normal Ranges and Variability of Novel Urinary Renal Biomarkers in Sprague-Dawley Rats: Comparison of Constitutive Values between Males and Females and across Assay Platforms
Normal Ranges and Variability of Novel Urinary Renal Biomarkers in Sprague-Dawley Rats: Comparison of Constitutive Values between Males and Females and across Assay Platforms
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DOI：
10.1177/0192623313520352
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发表时间：
2014-10-01
影响因子：
1.5
通讯作者：
Harpur, Ernie
中科院分区：
文献类型：
--
作者：
Gautier, Jean-Charles;Gury, Thierry;Harpur, Ernie
检查了雄性和雌性Sprague-Dawley大鼠在各种尿液生物标志物（包括7种最近合格的生物标志物）基础水平方面的差异。该数据来自3次从未给药大鼠中采集的尿液样本，该样本包含在庆大霉素肾毒性对尿液肾脏生物标志物影响的研究中，该研究在该期刊的一篇伴随文章中报告（Gautier et al. 2014）。评价了多种检测试剂盒（来自Rules Based Medicine [RBM]和Meso Scale Discovery [MSD]的9种单重检测试剂盒和2种多重平台）的性能，并推导出正常范围和变异性估计值。虽然RBM平台上的变异性通常大于其他检测试剂盒，但不同检测试剂盒的结果差异更显著。如果在单个生物标志物的测定之间观察到差异，则在两种性别中均观察到差异，并且在不同时间点采集的样本中一致。在检测试剂盒之间观察到一些生物标志物值的差异高达15倍，表明不应比较使用不同检测试剂盒生成的结果。对于8种生物标志物，有令人信服的证据表明存在性别差异。男性的总蛋白、β 2-微球蛋白、丛生蛋白、胱抑素-C、谷胱甘肽-S-转移酶（GST-）、金属蛋白酶组织抑制剂（TIMP-1）和血管内皮生长因子（VEGF）的基线值显著高于女性;女性的白蛋白值显著高于男性。β 2-微球蛋白、GST-和TIMP-1的性别差异最大（男性大于女性2- 11倍）。这些数据大大增加了在这一领域的知识有限的身体，并提供了一个有用的框架，这些生物标志物的诊断性能的性别差异的潜在相关性的评价。
Differences were examined between male and female Sprague-Dawley rats in basal levels of a wide range of urinary biomarkers, including 7 recently qualified biomarkers. The data were generated from urine samples collected on 3 occasions from untreated rats included in a study of the effect of gentamicin nephrotoxicity on urinary renal biomarkers, reported in a companion article in this journal (Gautier et al. 2014). The performance of multiple assays (9 singleplex assays and 2 multiplex platforms from Rules Based Medicine [RBM] and Meso Scale Discovery [MSD]) was evaluated, and normal ranges and variability estimates were derived. While variability was generally greater on the RBM platform than other assays, the more striking difference in the results from different assays was in magnitude. Where differences were observed between assays for an individual biomarker, they were seen in both sexes and consistent across samples collected at different time points. Differences of up to 15-fold were observed for some biomarker values between assays indicating that results generated using different assays should not be compared. For 8 biomarkers, there was compelling evidence for a sex difference. Baseline values in males were significantly higher than in females for total protein, 2-microglobulin, clusterin, cystatin-C, glutathione-S-transferase (GST-), tissue inhibitor of metalloproteinases (TIMP-1), and vascular endothelial growth factor (VEGF); female values were significantly higher than that of males for albumin. The largest sex differences (male greater than female by 2- to 11-fold) were seen with 2-microglobulin, GST-, and TIMP-1. These data add substantially to the limited body of knowledge in this area and provide a useful framework for evaluation of the potential relevance of sex differences in the diagnostic performance of these biomarkers.