title: Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.
abstract: Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning.
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka; Clinical Pharmacology and Toxicology Group, Professorial Medicine Unit, The Prince of Wales Clinical School, University of New South Wales, New South Wales, Australia; Department of Pharmacy, Faculty of Allied Health Sciences, University of Peradeniya, Sri Lanka; Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia; Department of Pharmacology, SOMS, Sydney Medical School, University of Sydney, New South Wales, Australia. Electronic address: fahim.cader@gmail.com.
authors.forename: Fahim
authors.initials: F
authors.lastname: Mohamed
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka; Clinical Pharmacology and Toxicology Group, Professorial Medicine Unit, The Prince of Wales Clinical School, University of New South Wales, New South Wales, Australia; Department of Pharmacology, SOMS, Sydney Medical School, University of Sydney, New South Wales, Australia. Electronic address: nicholas.buckley@sydney.edu.au.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Buckley
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. Electronic address: shalukajaya@yahoo.com.
authors.forename: Shaluka
authors.initials: S
authors.lastname: Jayamanne
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand; Emergency Department, Christchurch Hospital, Christchurch, New Zealand. Electronic address: john.pickering@icloud.com.
authors.forename: John W
authors.initials: JW
authors.lastname: Pickering
authors.affiliation: Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia. Electronic address: phyllip.peake@sesiahs.health.nsw.gov.au.
authors.forename: Philip
authors.initials: P
authors.lastname: Peake
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. Electronic address: chathura7@yahoo.com.
authors.forename: Chathura
authors.initials: C
authors.lastname: Palangasinghe
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. Electronic address: thilini.wijerathna@gmail.com.
authors.forename: Thilini
authors.initials: T
authors.lastname: Wijerathna
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. Electronic address: rmiu.ratnayake@yahoo.com.
authors.forename: Indira
authors.initials: I
authors.lastname: Ratnayake
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. Electronic address: fathimashihana@gmail.com.
authors.forename: Fathima
authors.initials: F
authors.lastname: Shihana
authors.affiliation: Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia; Department of Medicine, University of Otago, Christchurch, New Zealand. Electronic address: z.endre@unsw.edu.au.
authors.forename: Zoltan H
authors.initials: ZH
authors.lastname: Endre
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis* / Q000401:mortality; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D015415:Biomarkers; D051152:Clusterin / Q000652:urine; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D010269:Paraquat / Q000506:poisoning*; D011518:Proto-Oncogene Proteins / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C495242:CLU protein, human; D051152:Clusterin; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine; D010269:Paraquat
keywords: Acute kidney injury; Biomarker thresholds; Paraquat poisoning; Structural biomarkers; Urinary clusterin