Gautier Jean-Charles, Gury Thierry, Guffroy Magali, Khan-Malek Richard, Hoffman David, Pettit Syril, Harpur Ernie
Sanofi R&D, Paris, France
Sanofi R&D, Paris, France.
Toxicol Pathol. 2014 Oct;42(7):1092-104. doi: 10.1177/0192623313520352. Epub 2014 Mar 26.
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, β2-microglobulin, clusterin, cystatin-C, glutathione-S-transferase (GST-α), 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 β2-microglobulin, GST-α, 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.
研究了雄性和雌性Sprague-Dawley大鼠在多种尿液生物标志物基础水平上的差异，其中包括7种最近获批的生物标志物。这些数据来自于在一项关于庆大霉素肾毒性对尿液肾脏生物标志物影响的研究中，从未经治疗的大鼠身上三次采集的尿液样本，该研究在本期刊的一篇相关文章中有所报道（Gautier等人，2014年）。评估了多种检测方法（9种单重检测方法以及来自基于规则医学公司[RBM]和梅索尺度发现公司[MSD]的2种多重检测平台）的性能，并得出了正常范围和变异性估计值。虽然RBM平台上的变异性通常比其他检测方法更大，但不同检测方法结果中更显著的差异在于数值大小。对于单个生物标志物，在不同检测方法之间观察到差异时，在两性中均可见，并且在不同时间点采集的样本中具有一致性。某些生物标志物的值在不同检测方法之间观察到高达15倍的差异，这表明不应比较使用不同检测方法产生的结果。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。在总蛋白、β2-微球蛋白、簇集蛋白、胱抑素-C、谷胱甘肽-S-转移酶（GST-α）、金属蛋白酶组织抑制剂（TIMP-1）和血管内皮生长因子（VEGF）方面，雄性的基线值显著高于雌性；白蛋白方面，雌性的值显著高于雄性。β2-微球蛋白、GST-α和TIMP-1的性别差异最大（雄性比雌性高2至11倍）。这些数据极大地丰富了该领域有限的知识体系，并为评估这些生物标志物诊断性能中性别差异的潜在相关性提供了有用的框架。
