Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion

• Only functional biomarkers (sCr and sCysC) predicted death following paraquat poisoning.
• Urinary CysC and clusterin were useful early biomarkers (at 8 and 16 h) in diagnosing the later onset of functional AKI.
• Use of urinary CysC and clusterin within the first day after ingestion may guide early intervention for reno-protection.
• The increase in specific renal injury biomarkers was consistent with the mechanistic pathways of paraquat induced-nephrotoxicity.
• Point-of-care biomarker detection would be required to enable early intervention in selected patients in rural Asia.

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 24 h 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 16 h. 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 16–24 h may guide early intervention for reno-protection in less severe paraquat poisoning.