Evaluation of novel renal biomarkers with a cisplatin model of kidney injury: gender and dosage differences.

Pinches M, Betts C, Bickerton S, Burdett L, Thomas H, Derbyshire N, Jones HB, Moores M.
Journal   Toxicol Pathol.
Species  
Analytes Measured   Albumin , GSTYb1 , HAVCR1 KIM-1 , Osteopontin , RPA-1
Matrix Tested   Urine
Year   2012
Volume   40
Page Numbers   522-533
Application   Toxicology
Abstract
A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We use two novel multiplex assays to quantify biomarker concentration in multiple urine collections made prior to and following administration of cisplatin, a common nephrotoxicant, to rats. We investigate the correlation of the magnitude of biomarker changes with the severity of histopathological observations and explore the relationship of these to both dose and sex. The novel biomarkers evaluated are urinary albumin, alpha glutathione s-transferase (α-GST), glutathione S-transferase-yb1 (GSTYb1), lipocalin-2, kidney injury molecule-1 (KIM-1), osteopontin, and renal papillary antigen 1 (RPA-1) and plasma cystatin C, alongside the traditional biomarkers of plasma urea, creatinine, and urinary n-acetyl-beta-d-glucosaminidase (NAG), total protein, and glucose. We show for all time points, and for almost all doses, that male rats consistently had either more severely graded or a higher incidence of histologically observed lesions than females; that changes in urinary glucose, total urinary protein, NAG, and the novel urinary biomarkers albumin, osteopontin, and KIM-1 are clearly temporally associated; and that changes are related to the severity of injury. We also found that receiver operating characteristic curve analysis and area under the curve are significantly higher than urea or creatinine for all new biomarkers except aGST, GSTYb1, cystatin c, and total protein in both sexes.

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