TY - JOUR
T1 - Strain-related Differences in Urine Composition of Male Rats of Potential Relevance to Urolithiasis
AU - Tannehill-Gregg, Sarah H.
AU - Dominick, Mark A.
AU - Reisinger, Amy J.
AU - Moehlenkamp, Jeffrey D.
AU - Waites, C. Robbie
AU - Stock, David A.
AU - Sanderson, Thomas P.
AU - Cohen, Samuel M.
AU - Arnold, Lora L.
AU - Schilling, Beth E.
PY - 2009/4
Y1 - 2009/4
N2 - In carcinogenicity studies with PPAR γ and α/γ 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.
AB - In carcinogenicity studies with PPAR γ and α/γ 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.
KW - composition
KW - rat
KW - strain
KW - urinalysis
KW - urine
KW - urolithiasis
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U2 - 10.1177/0192623309332990
DO - 10.1177/0192623309332990
M3 - Article
C2 - 19380840
AN - SCOPUS:67049088308
VL - 37
SP - 293
EP - 305
JO - Toxicologic Pathology
JF - Toxicologic Pathology
SN - 0192-6233
IS - 3
ER -