Identification of contaminant interferences which cause positive urine reagent test strip reactions in a cage setting for the laboratory-housed nonhuman primate, Beagle dog, and Sprague–Dawley rat

Abstract

Background: 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. Objectives: The objective of this study was to identify cage pan contaminants which could cause positive reagent test strip reactions. Methods: 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. Results: 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. Conclusions: 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.