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1.  Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery 
Kidney international  2013;85(2):431-438.
Biomarkers for acute kidney injury (AKI) have been used to predict the progression of AKI but a systematic comparison of the prognostic ability of each biomarkers alone or in combination has not been performed. In order to assess this, we measured the concentration of 32 candidate biomarkers in the urine of 95 patients with AKIN stage 1 after cardiac surgery. Urine markers were divided into eight groups based on the putative pathophysiologic mechanism they reflect. We then compared the ability of the markers alone or in combination to predict the primary outcome of worsening AKI or death (23 patients) and the secondary outcome of AKIN stage 3 or death (13 patients). IL-18 was the best predictor of both outcomes (AUC of 0.74 and 0.89). L-FABP (AUC of 0.67 and 0.85), NGAL (AUC of 0.72 and 0.83) and KIM-1 (AUC of 0.73 and 0.81) were also good predictors. Correlation between most of the markers was generally related to their predictive ability but KIM-1 had a relatively weak correlation with other markers. The combination of IL-18 and KIM-1 had a very good predictive value with an AUC of 0.93 to predict AKIN 3 or death. Thus, combination of IL-18 and KIM-1 would result in improved identification of high risk patients for enrollment in clinical trials.
doi:10.1038/ki.2013.333
PMCID: PMC3880389  PMID: 24005224
Kidney; renal failure; Outcomes; Postoperative care; Risk assessment; predictive modeling; biomarker discovery; Surgery; complications; Interleukin 18; Interleukin 6; Vascular endothelial growth factor; Monocyte chemotactic protein-1; Interleukin 1 receptor antagonist; Interleukin 8; Growth related oncogene alpha; Leukemia inhibitory factor; Interleukin 10; Eotaxin; Vascular cell adhesion molecule-1; RANTES; Regulated on activation; normal T cell expressed and secreted; Tumor necrosis factor alpha; Macrophage inflammatory protein-1alpha; Neutrophil gelatinase associated lipocalin; Kidney injury molecule-1; Liver type fatty acid binding protein; Hepatocyte growth factor; Netrin-1; Clusterin; Fetuin-A; Cystatin C; Albumin; Beta-2-microglobulin; Retinol binding protein; Alpha-1 antitrypsin; 8-Isoprostane; Trefoil factor 3; N-acetyl-beta-D-glucosaminidase; TRAIL; TNF-related apoptosis-inducing ligand
2.  Overcoming the Effects of Matrix Interference in the Measurement of Urine Protein Analytes 
Biomarker Insights  2012;7:1-8.
Using multiplex bead assays to measure urine proteins has a great potential for biomarker discovery, but substances in urine (the matrix) can interfere with assay measurements. By comparing the recovery of urine spiked with known quantities of several common analytes, this study demonstrated that the urine matrix variably interfered with the accurate measurement of low abundance proteins. Dilution of the urine permitted a more accurate measure of these proteins, equivalent to the standard dilution technique when the diluted analytes were above the limits of detection of the assay. Therefore, dilution can be used as an effective technique for over-coming urine matrix effects in urine immunoassays. These results may be applicable to other biological fluids in which matrix components interfere with assay performance.
doi:10.4137/BMI.S8703
PMCID: PMC3290108  PMID: 22403482
biomarkers; body fluids urine; analysis/urine; standard addition; assay validation

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