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Strain-related Differences in Urine Composition of Male Rats of Potential Relevance to Urolithiasis

¹ Bristol-Myers Squibb Research & Development, Department of Drug Safety Evaluation, Mount Vernon, Indiana, USA
² Bristol-Myers Squibb Research & Development, Department of Global Biometric Sciences, Wallingford, Connecticut, USA
³ Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
⁴ SABIC Innovative Plastics, Mount Vernon, Indiana, USA

Correspondence: Sarah Tannehill-Gregg, Drug Safety Evaluation, Bristol-Myers Squibb, 2400 West Lloyd Expressway, P3, Evansville, IN 47721; e-mail:sarah.tannehill-gregg{at}bms.com.

In carcinogenicity studies with PPAR and / agonists, urinary bladder tumors have been reported in Harlan Sprague-Dawley (HSD) and Charles River Sprague-Dawley (SD) but not Wistar (WI) rats, with urolithiasis purported to be the inciting event. In two 3-month studies, the authors investigated strain-related differences in urine composition by sampling urine multiple times daily. Urine pH, electrolytes, creatinine, protein, citrate and oxalate levels, and serum citrate were assessed; urine sediment was analyzed by scanning electron microscopy and energy dispersive x-ray spectroscopy. HSD rats had significantly higher urine calcium than SD or WI rats, primarily as calcium phosphate-containing precipitate. When compared to SD rats, HSD rats had lower urine volume, higher urine protein, and a comparable (week 4) to lower (week 13) burden of MgNH₄PO₄ aggregates. Relative to WI rats, HSD rats had higher urine protein and magnesium and lower serum and urine citrate. Overall, the susceptibility to urolithiasis in male rats was HSD > SD > WI; this was likely due to strain-related differences in the amount of urine protein (a nidus for crystal formation), lithogenic ions, citrate (an inhibitor of lithogenesis), and/or volume. Strain-related differences in urine composition need to be considered when interpreting the outcome of studies with compounds that alter urine composition.

Key Words: urine • composition • rat • urolithiasis • strain • urinalysis

Abbreviations: HSD, Harlan Sprague-Dawley • PPAR, peroxisome proliferator-activated receptor • SD, Charles River Sprague-Dawley • WI, Wistar

Toxicologic Pathology, Vol. 37, No. 3, 293-305 (2009)
DOI: 10.1177/0192623309332990


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