Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury.

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2019-07
Authors
Pais, Gwendolyn M
Avedissian, Sean N
O'Donnell, J Nicholas
Rhodes, Nathaniel J
Lodise, Thomas P
Prozialeck, Walter C
Lamar, Peter C
Cluff, Cameron
Gulati, Anil
Fitzgerald, Julie C
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Abstract
Urinary biomarkers are superior to serum creatinine for defining onset and extent of kidney injury. This study classifies the temporal predictive ability of biomarkers for vancomycin-induced kidney injury (VIKI) as defined by histopathologic damage. Male Sprague-Dawley rats (n = 125) were randomized to receive 150 to 400 mg/kg of body weight/day vancomycin via once or twice daily intraperitoneal injection over 1, 3, or 6 days. Urine was collected once during the 24 h prior to euthanasia or twice for rats treated for 6 days. Receiver operating characteristic (ROC) curves were employed to assess the urinary biomarker performances of kidney injury molecule 1 (KIM-1), clusterin, osteopontin (OPN), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) to predict histopathologically defined VIKI (using a national standard pathological assessment scheme from hematoxylin and eosin stained kidneys). Urinary KIM-1, clusterin, and OPN outperformed cystatin C and NGAL with regard to sensitivity and specificity. For the earliest injury, urinary KIM-1 (area under the receiver operating characteristic curve [AUC], 0.662; P < 0.001) and clusterin (AUC, 0.706; P < 0.001) were the most sensitive for predicting even low-level histopathologic damage at 24 h compared to NGAL. KIM-1 and clusterin are the earliest and most sensitive predictors of VIKI. As injury progresses, KIM-1, clusterin, and OPN best define the extent of damage.
Citation
Pais GM, Avedissian SN, O'Donnell JN, Rhodes NJ, Lodise TP, Prozialeck WC, Lamar PC, Cluff C, Gulati A, Fitzgerald JC, Downes KJ, Zuppa AF, Scheetz MH. Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury. Antimicrob Agents Chemother. 2019 Jun 24;63(7):e00079-19. doi: 10.1128/AAC.00079-19. PMID: 30988153; PMCID: PMC6591602.
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K23 HD091365/HD/NICHD NIH HHS/United States , R15 AI105742/AI/NIAID NIH HHS/United States