Siska William D, Meyer Dennis J, Schultze Albert E, Brandoff Catherine
Charles River Laboratories, Reno, NV, USA.
Lilly Research Laboratories, Department of Pathology, A Division of Eli Lilly and Company, Indianapolis, IN, USA.
Vet Clin Pathol. 2017 Mar;46(1):85-90. doi: 10.1111/vcp.12427. Epub 2016 Nov 7.
A high incidence of unexplained positive urine reagent test strip reactions was observed in healthy, untreated laboratory-housed nonhuman primates, Beagle dogs, and Sprague-Dawley rats. Exposure of urine to cage pan contaminants was the suspected cause of the positive reactions.
The objective of this study was to identify cage pan contaminants which could cause positive reagent test strip reactions.
Contaminated urine was simulated by exposing water samples to cage pan contaminants, including cleaning solutions, feces from nonhuman primates, Beagle dogs, and Sprague-Dawley rats, certified laboratory animal diets, and dietary enrichments (vegetables, fruits, and food treats). Ten samples were prepared for each contaminant and analyzed for blood, glucose, bilirubin, ketones, pH, protein, urobilinogen, nitrite, and leukocyte esterase using commercially available urine reagent test strips and an automated urine chemistry analyzer.
Positive reactions were common for all but one analyte and frequently associated with multiple contaminants. Blood, glucose, and protein reactions had the highest incidence and/or strongest positive reactions. Positive reactions for other reagent test strip analytes were observed, but generally of lower incidence and magnitude.
We identified a high incidence of contaminant interferences in a water matrix causing positive reagent test strip reactions, primarily for the blood, glucose, and protein reactions. These findings highlight the potential limited value of urine reagent test strip assays as reliable biomarkers for detecting kidney toxicity in nonclinical studies, and imply that urine collection methods that minimize exposure to contaminants will likely improve the diagnostic validity of reagent test strip assays.
在健康、未经治疗的实验室内饲养的非人灵长类动物、比格犬和斯普拉格-道利大鼠中,观察到尿试剂试纸条反应呈阳性且原因不明的情况发生率较高。尿液接触笼底污染物被怀疑是导致阳性反应的原因。
本研究的目的是确定可能导致试剂试纸条反应呈阳性的笼底污染物。
通过将水样暴露于笼底污染物来模拟受污染的尿液,这些污染物包括清洁溶液、非人灵长类动物、比格犬和斯普拉格-道利大鼠的粪便、经认证的实验动物饲料以及膳食补充剂(蔬菜、水果和零食)。每种污染物制备10个样本,并使用市售尿试剂试纸条和自动尿液化学分析仪分析血液、葡萄糖、胆红素、酮体、pH值、蛋白质、尿胆原、亚硝酸盐和白细胞酯酶。
除一种分析物外,所有分析物的阳性反应都很常见,并且经常与多种污染物相关。血液、葡萄糖和蛋白质反应的发生率最高和/或阳性反应最强。观察到其他试剂试纸条分析物的阳性反应,但发生率和强度通常较低。
我们发现水基质中污染物干扰导致试剂试纸条反应呈阳性的情况发生率较高,主要是血液、葡萄糖和蛋白质反应。这些发现突出了尿试剂试纸条检测在非临床研究中作为检测肾脏毒性可靠生物标志物的潜在有限价值,并表明尽量减少污染物暴露的尿液收集方法可能会提高试剂试纸条检测的诊断有效性。