Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

Liu, Kathleen D.; Siew, Edward D.; Reeves, W. Brian; Himmelfarb, Jonathan; Go, Alan S.; Hsu, Chi-yuan; Bennett, Michael; Devarajan, Prasad; İkizler, T. Alp; Kaufman, James S.; Kimmel, Paul L.; Chinchilli, Vernon M.; Parikh, Chirag R.

doi:10.1371/journal.pone.0164832

Cited by 20 publications

(15 citation statements)

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“…S100 proteins also possess some practical properties of an ideal biomarker. S100 proteins seem to be quite stable for measurement, both in serum and in urine, even after prolonged storage, in line with prior findings for NGAL [ 36 ]. Several studies have also documented that immunosuppressive drugs do not affect S100A8/9 expression [ 11 , 29 ].…”

Section: Discussionsupporting

confidence: 87%

Urine S100 proteins as potential biomarkers of lupus nephritis activity

et al. 2017

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BackgroundImproved, noninvasive biomarkers are needed to accurately detect lupus nephritis (LN) activity. The purpose of this study was to evaluate five S100 proteins (S100A4, S100A6, S100A8/9, and S100A12) in both serum and urine as potential biomarkers of global and renal system-specific disease activity in childhood-onset systemic lupus erythematosus (cSLE).MethodsIn this multicenter study, S100 proteins were measured in the serum and urine of four cSLE cohorts and healthy control subjects using commercial enzyme-linked immunosorbent assays. Patients were divided into cohorts on the basis of biospecimen availability: (1) longitudinal serum, (2) longitudinal urine, (3) cross-sectional serum, and (4) cross-sectional urine. Global and renal disease activity were defined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K renal domain score. Nonparametric testing was used for statistical analysis, including the Wilcoxon signed-rank test, Kruskal-Wallis test, Mann-Whitney U test, and Spearman’s rank correlation coefficient.ResultsAll urine S100 proteins were elevated in patients with active LN compared with patients with active extrarenal disease and healthy control subjects. All urine S100 protein levels decreased with LN improvement, with S100A4 demonstrating the most significant decrease. Urine S100A4 levels were also higher with proliferative LN than with membranous LN. S100A4 staining in the kidney localized to mononuclear cells, podocytes, and distal tubular epithelial cells. Regardless of the S100 protein tested, serum levels did not change with cSLE improvement.ConclusionsHigher urine S100 levels are associated with increased LN activity in cSLE, whereas serum S100 levels do not correlate with disease activity. Urine S100A4 shows the most promise as an LN activity biomarker, given its pronounced decrease with LN improvement, isolated elevation in urine, and positive staining in resident renal cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1444-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 87%

Urine S100 proteins as potential biomarkers of lupus nephritis activity

et al. 2017

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“…Mixed effects models were used to determine the effect of storage time on biomarker levels (Supplemental Figure 1, Supplemental Table 1). 26 We performed multivariate analyses to examine the association between the covariates of age, sex, race, preoperative GFR, RACHS-1, and CPB time with the outcome of AKI progression. We determined the adjusted odds ratio (using logistic regression) for biomarkers to predict AKI progression.…”

Section: Statistical Analysesmentioning

confidence: 99%

Biomarkers of AKI Progression after Pediatric Cardiac Surgery

Greenberg

Zappitelli

Jia

et al. 2018

JASN

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As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass. On the first day of serum creatinine-defined AKI, we measured urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (≥2 consecutive days). In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively. If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.

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“…Mixedeffects models were used to determine the effect of storage time on biomarker levels (Supplemental Table 1 and Supplemental Figures 1a, 1b, 1c). 13 Because 95% of AKI occurred in the first 2 postoperative days, we evaluated associations between preoperative and first postoperative biomarker measurements with AKI. 1 From our prior work on other biomarkers in this cohort and the understanding that kidney function continues to mature up to 2 years of age, we suspected significant differences in biomarker concentrations for children <2 vs !2 years old.…”

Section: Discussionmentioning

confidence: 99%