Abstract
Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = −0.71; cystatin C, r = −0.70; TNF-R1, r = −0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI.
Highlights
As the first treatment option for methicillin-resistant Staphylococcus aureus (MRSA) infection [1], vancomycin is a commonly used antimicrobial agent whose use has been increasing with the growing prevalence of MRSA infection [2,3]
We evaluated the value of serum concentrations of biomarkers that have been identified as potential urinary biomarkers for Vancomycin-induced kidney injury (VIKI) and other drug-induced kidney injury (trefoil factor-3 (TFF3)) for diagnosis of VIKI [31,32,33]
The serum creatinine (sCr) level was higher in the VIKI group compared with non-VIKI and healthy control (HC) groups; estimated glomerular filtration rate (GFR) was lower in the VIKI group (VIKI vs. non-VIKI vs. HC, 42 mL/min/1.73 m2 vs. 107 mL/min/1.73 m2 vs. 85 mL/min/1.73 m2, p < 0.001)
Summary
As the first treatment option for methicillin-resistant Staphylococcus aureus (MRSA) infection [1], vancomycin is a commonly used antimicrobial agent whose use has been increasing with the growing prevalence of MRSA infection [2,3]. Elevation in sCr concentration is affected by non-renal factors independent of kidney function [9,10] and lags several days behind actual change in kidney function [11] It reflects the downstream effect from a reduction in glomerular filtration rate (GFR) rather than an indicator of VIKI itself. Its value as an indicator of VIKI has yet to be evaluated In this present study, we evaluated the value of serum concentrations of biomarkers that have been identified as potential urinary biomarkers for VIKI (osteopontin, NGAL, clusterin) and other drug-induced kidney injury (trefoil factor-3 (TFF3)) for diagnosis of VIKI [31,32,33]. We aim to identify candidate serum biomarkers for the diagnosis of VIKI
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