Harrill2: Drug study: Survey of kidney injury due to DB289 treatment in females of 34 inbred strains of mice (2012)

Harrill AH, Desmet KD, Wolf KK, Bridges AS, Eaddy JS, Kurtz CL, Hall JE, Paine MF, Tidwell RR, Watkins PB. A Mouse Diversity Panel Approach Reveals the Potential for Clinical Kidney Injury Due to DB289 Not Predicted by Classical Rodent Models. Toxicol Sci. 2012 Dec;130(2):416-26. doi: 10.1093/toxsci/kfs238. Epub 2012 Aug 31.   PubMed 22940726     FullText


         
Notes
"Difference" measurements were computed by MPD from the strain means (fold change, D289 over control) and are available for download in a separate supplementary file.

MPD curation note: DB289 was previously tested in clinical trials to treat African trypanosomiasis. However, the trial was terminated when subjects developed severe kidney injury, an effect not predicted from preclinical testing. This project (Harrill2) highlights the utility of inbred strains to predict clinically relevant toxicities to drugs prior to clinical trials.


Harrill2 downloads
• Download Harrill2 project data set     one row per animal, one column per trait
• Download Harrill2 strain means, SD, N, etc.     one row per strain/sex/measure
• Harrill2 supplementary data
Participants Alison Harrill       University of Arkansas for Medical Sciences Little Rock, AR
ContactAlison Harrill     AHHarrill@uams.edu     Lab web site
AcknowledgementsFunding provided by the Bill and Melinda Gates Foundation.
Project type Phenotype strain survey data set
MPD identifiersHarrill2     MPD:441
Data changelog No updates/corrections.       Initial release date: 12/2012.
Formatted citation
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Mice received ten days of oral treatment with DB289 (pafuramidine) or vehicle. Blood chemistry and urinalysis were performed. Urine biomarkers of kidney injury were measured and organs weighed.



Summary of procedures that were conducted
• body weight DB289-treated vs. control.
• metabolic panel Blood urea nitrogen, alanine transaminase, creatinine. DB289-treated vs. control.
• urinalysis Urine volume, creatinine. DB289-treated vs. control.
• organ weights Kidney and liver weights. DB289-treated vs. control.
• biomarker quantification Kidney injury molecule 1 (KIM-1). DB289-treated vs. control.
• drug and metabolite quantification Kidney metabolite (DB75) concentration. DB289-treated vs. control.
Mice: inbred   34 strains   ♀   age 6-8wks   2 cohorts

Select table page: First Prev Next Last
Data set MPD ID Procedure / Protocol Drug or Challenge Phenotype Measure Panel No. of Strains Sex Age Sample Size (Avg)
    Harrill2 44101 body weight DB289 body weight at start of testing   [g]     control    DB289 inbred 34 f 6-8wks N=5
    Harrill2 44103 body weight DB289 body weight at end of testing   [g]     control    DB289 inbred 34 f 6-8wks N=5
    Harrill2 44105 body weight DB289 fold change in body weight over testing period   [ratio]     control    DB289    difference inbred 34 f 6-8wks N=5
    Harrill2 44111 metabolic panel DB289 alanine transaminase (serum ALT)   [IU/L]     control    DB289    difference inbred 34 f 6-8wks N=5
    Harrill2 44115 metabolic panel DB289 blood urea nitrogen (serum BUN)   [mg/dL]     control    DB289    difference inbred 34 f 6-8wks N=5
    Harrill2 44121 metabolic panel DB289 creatinine (serum CREA)   [mg/dL]     control    DB289    difference inbred 34 f 6-8wks N=5
    Harrill2 44125 urinalysis DB289 urine volume   [mL]     control    DB289    difference inbred 33 f 6-8wks N=5
    Harrill2 44131 urinalysis DB289 creatinine (urine CREA)   [mg/mL]     control    DB289    difference inbred 31 f 6-8wks N=5
    Harrill2 44135 biomarker quantification DB289 urine kidney injury molecule 1 (KIM-1)   [pg]     control    DB289    difference inbred 32 f 6-8wks N=5
    Harrill2 44141 organ weights DB289 kidney (left) weight   [g]     control    DB289 inbred 34 f 6-8wks N=5
    Harrill2 44144 organ weights DB289 kidney (right) weight   [g]     control    DB289 inbred 34 f 6-8wks N=5
    Harrill2 44148 organ weights DB289 kidney (both) weight   [g]     control    DB289 inbred 34 f 6-8wks N=5
    Harrill2 44151 organ weights DB289 total kidney weight as percent of body weight   [%]     control    DB289    difference inbred 34 f 6-8wks N=5
    Harrill2 44155 drug and metabolite quantification DB289 kidney metabolite (DB75) concentration   [µM]     control    DB289 inbred 23 f 6-8wks N=4
    Harrill2 44161 organ weights DB289 liver weight at sacrifice   [g]     control    DB289 inbred 34 f 6-8wks N=5
    Harrill2 44165 organ weights DB289 liver weight as percent of body weight   [%]     control    DB289    difference inbred 34 f 6-8wks N=5
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