Kidney biomarkers in MCPA-induced acute kidney injury in rats : reduced clearance enhances early biomarker performance
Date
2014
Authors
Wunnapuk, K.
Liu, X.
Gobe, G.C.
Endre, Z.H.
Peake, P.W.
Grice, J.E.
Roberts, M.S.
Buckley, N.A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Toxicology Letters, 2014; 225(3):467-478
Statement of Responsibility
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Data source: Supplementary data, https://ars.els-cdn.com/content/image/1-s2.0-S0378427414000290-mmc1.pdf
Access Status
Rights
Copyright 2014 Elsevier Ireland
Access Condition Notes: Accepted manuscript only available on Open Access