title: Renal biomarkers predict nephrotoxicity after paraquat.
abstract: Paraquat is a widely used herbicide which has been involved in many accidental and intentional deaths. Nephrotoxicity is common in severe acute paraquat poisoning. We examined seven renal injury biomarkers, including cystatin-C, kidney injury molecule-1, β2-microglobulin, clusterin, albumin, neutrophil gelatinase-associated lipocalin and osteopontin, to develop a non-invasive method to detect early renal damage and dysfunction and to compare with the conventional endogenous marker creatinine. Male Wistar rats were dosed orally with four different doses of paraquat, and the biomarker patterns in urine and plasma were investigated at 8, 24 and 48h after paraquat exposure. By Receiver Operating Characteristic analysis, urinary kidney injury molecule-1 was the best marker at predicting histological changes, with areas under the Receiver Operating Characteristic curve of 0.81 and 0.98 at 8 and 24h (best cut-off value>0.000326μg/ml), respectively. Urinary kidney injury molecule-1, urinary albumin and urinary Cystatin-C elevations correlated with the degree of renal damage and injury development. Further study is required to compare biomarkers changes in rats with those seen in human poisoning.
authors: Therapeutics Research Centre, School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors: Klintean
authors: K
authors: Wunnapuk
authors: Xin
authors: X
authors: Liu
authors: Philip
authors: P
authors: Peake
authors: Glenda
authors: G
authors: Gobe
authors: Zoltan
authors: Z
authors: Endre
authors: Jeffrey E
authors: JE
authors: Grice
authors: Michael S
authors: MS
authors: Roberts
authors: Nicholas A
authors: NA
authors: Buckley
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000419:Albuminuria / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015815:Cell Adhesion Molecules / Q000097:blood / Q000652:urine; D051152:Clusterin / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D055316:Cystatin C / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000652:urine; D008297:Male; D053495:Osteopontin / Q000097:blood / Q000652:urine; D010269:Paraquat / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis; D001613:beta 2-Microglobulin / Q000097:blood / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D051152:Clusterin; D003404:Creatinine; D055316:Cystatin C; D000071068:Lipocalin-2; D054834:Lipocalins; D053495:Osteopontin; D010269:Paraquat; D011518:Proto-Oncogene Proteins; D012709:Serum Albumin; D001613:beta 2-Microglobulin; C525032:Cst3 protein, rat; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat
keywords: Acute kidney injury; Creatinine; Cystatin-C; Kidney injury molecule-1; Paraquat; Renal biomarker