Kidney biomarkers in MCPA-induced acute kidney injury in rats: reduced clearance enhances early biomarker performance

Wunnapuk, Klintean, Liu, Xin, Gobe, Glenda C., Endre, Zoltan H., Peake, Philip W., Grice, Jeffrey E., Roberts, Michael S. and Buckley, Nicholas A. (2014) Kidney biomarkers in MCPA-induced acute kidney injury in rats: reduced clearance enhances early biomarker performance. Toxicology Letters, 225 3: 467-478. doi:10.1016/j.toxlet.2014.01.018


Author Wunnapuk, Klintean
Liu, Xin
Gobe, Glenda C.
Endre, Zoltan H.
Peake, Philip W.
Grice, Jeffrey E.
Roberts, Michael S.
Buckley, Nicholas A.
Title Kidney biomarkers in MCPA-induced acute kidney injury in rats: reduced clearance enhances early biomarker performance
Journal name Toxicology Letters   Check publisher's open access policy
ISSN 0378-4274
1879-3169
Publication date 2014-03-21
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.toxlet.2014.01.018
Open Access Status Not Open Access
Volume 225
Issue 3
Start page 467
End page 478
Total pages 12
Place of publication Shannon, Co. Clare, Ireland
Publisher Elsevier
Language eng
Abstract For improved early detection and assessment of severe acute kidney damage following accidental or intentional ingestion of the herbicide MCPA, we compared a panel of 14 novel kidney injury biomarkers with plasma creatinine. Male Wistar rats received four different oral doses of MCPA and plasma and urine biomarker levels were measured at 8, 24 and 48 h after MCPA exposure. Diagnostic performances using absolute levels, urine levels normalized to urine creatinine or urinary excretion rate were determined by ROC analysis. Plasma creatinine remained the best early biomarker for predicting histological changes at 48 h. The performance of plasma cystatin C in mirroring kidney function was similar to that of plasma creatinine. While urine concentrations were generally less predictive, normalization by urine creatinine greatly improved the performance of several biomarkers. This may be due to an apparent amplification of the biomarker signal on normalizing to creatinine, in the presence of a declining glomerular filtration rate prior to reaching steady state. Normalized 8 h osteopontin and albumin concentrations outperformed other normalized biomarkers in predicting histological changes at later times. Normalized urinary kidney injury molecule-1 at 48 h also correlated well with the degree of kidney damage.
Keyword 4-Chloro-2-methylphenoxyacetic acid
MCPA
Acute kidney injury
Kidney injury molecule-1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
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