Evaluation of clinically available renal biomarkers in critically ill adults: a prospective multicenter observational study

Deng, Yulin; Chi, Ruibin; Chen, Shenglong; Ye, Heng; Yuan, Jing; Wang, Lin; Zhai, Yi; Gao, Lu; Zhang, Danqing; Hu, Linhui; Lv, Bo; Lv, Yi; Sun, Cheng; Yang, Xiao; Zou, Xia; Chen, Chunbo

doi:10.1186/s13054-017-1626-0

Cited by 41 publications

(57 citation statements)

References 49 publications

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“…87 In a recent large prospective observational study performed in critically ill adult intensive care unit (ICU) patients, urine NAG levels alone allowed weak to moderate prediction of AKI, severe AKI, and ICU mortality (AUCs, 0.65, 0.71, and 0.79, respectively). 88 α-1-microglobulin (A1M) is a 27-kDa plasma protein produced by the liver. It has an immunoregulatory role and is considered to be an anti-oxidant that can scavenge pro-oxidant heme groups.…”

Section: Q18mentioning

confidence: 99%

Proteomics and Metabolomics for AKI Diagnosis

Marx

Metzger

Pejchinovski

et al. 2018

Seminars in Nephrology

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Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI. The detection of AKI in hospitalized patients implies the need for early, accurate, robust, and easily accessible biomarkers of AKI evolution and outcome prediction because only a narrow window exists to implement the earlier-described measures. Even more challenging is the multifactorial origin of AKI and the fact that the changes of molecular expression induced by AKI are difficult to distinguish from those of the diseases associated or causing AKI as shock or sepsis. During the past decade, a considerable number of protein biomarkers for AKI have been described and we expect from recent advances in the field of omics technologies that this number will increase further in the future and be extended to other sorts of biomolecules, such as RNAs, lipids, and metabolites. However, most of these biomarkers are poorly defined by their AKI-associated molecular context. In this review, we describe the state-of-the-art tissue and biofluid proteomic and metabolomic technologies and new bioinformatics approaches for proteomic and metabolomic pathway and molecular interaction analysis. In the second part of the review, we focus on AKI-associated proteomic and metabolomic biomarkers and briefly outline their pathophysiological context in AKI.

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Section: Q18mentioning

confidence: 99%

Proteomics and Metabolomics for AKI Diagnosis

Marx

Metzger

Pejchinovski

et al. 2018

Seminars in Nephrology

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“…The reason for this result may be that indicators with different characteristics have different sensitivities and specificities, and a reasonable combination between them can improve the diagnostic performance. This shared similar mechanism with Deng's research [30], in which the investigator combined a panel of a functional marker (sCysC) and a tubular injury marker (uNAG) to predict outcomes in patients with severe AKI, demonstrating superior discriminating performance compared to sCysC and uNAG alone.…”

Section: Discussionmentioning

confidence: 59%

Dysbiosis of intestinal microbiota to predict in-hospital mortality in critically ill patients: results of a prospective observational cohort study

Hu³

et al. 2020

Preprint

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Background: Despite the essential functions of the intestinal microbiota in human physiology, little research has been reported on the gut microbiota alteration in intensive care patients. This investigation aimed to explore the dysbacteriosis of intestinal flora in critically ill patients, and evaluate the prognostic performance of this dysbiosis to predict in-hospital mortality. Methods: A prospective cohort of patients were consecutively recruited at Intensive Care Units (ICUs) in Guangdong Provincial People's Hospital from March 2017 through October 2017. Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were assessed, and fecal samples were taken for examination within 24 hours of ICU admission. The taxonomic composition of intestinal microbiome was determined using 16S rDNA gene sequencing. Patients were divided into survival and death group based on the outcomes in hospital. The two groups were statistically compared using the independent samples t test and Metastats analysis. Genera of bacteria showing significantly different abundance between groups were assessed for predictors of in-hospital death. The prognostic value of bacterial abundance alone and in combination with APACHE II or SOFA score were evaluated using the area under the receiver operating characteristic curve (AUROC). Results: Among the 61 patients that were examined, a total of 12 patients (19.7%) died during hospital stay. Bifidobacterium differed significantly in abundance between survival and death group ( P =0.031). The AUROC of Bifidobacterium abundance identifying in-hospital death at a cut-off probability of 0.0041 was 0.718 (95% confidence interval [CI], 0.588-0.826). The panel of Bifidobacterium abundance plus SOFA (AUROC, 0.882; 95% CI, 0.774-0.950) outperformed SOFA (AUROC, 0.649; 95% CI, 0.516-0.767; P =0.012) and Bifidobacterium abundance alone ( P =0.007). The panel of Bifidobacterium abundance plus APACHE II (AUROC, 0.876; 95% CI, 0.766-0.946) outperformed APACHE II (AUROC, 0.724; 95% CI, 0.595-0.831; P =0.035) and Bifidobacterium abundance alone ( P =0.012). Conclusions: Dysbiosis of intestinal microbiota with variable degree of reduction in Bifidobacterium abundance exhibits promising performance in predicting in-hospital mortality, and provides incremental prognostic value to existing scoring systems in the adult intensive care unit (ICU) setting.

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“…Here we have found for the first time that higher plasma cystatin C concentrations measured early in the course of ARDS are associated with higher mortality and that this association persists after adjustment for AKI defined by creatininebased criteria. Earlier studies reported that elevated cystatin C is associated with higher mortality in heterogenous cohorts of critically-ill patients (5,7,8), but prior to this study, this finding had not been validated in a large cohort of patients with ARDS. Additionally, to the best of our knowledge, this is the first study to test the association of cystatin C and mortality among critically ill patients cared for in North America.…”

Section: Discussionmentioning

confidence: 61%

“…Furthermore, plasma cystatin C measurements are clinically available in many institutions. Elevated cystatin C is associated with higher mortality in heterogenous cohorts of critically-ill patients (5,7,8), but this finding has not been studied in a large cohort of patients with ARDS.…”

mentioning

confidence: 99%

Higher Plasma Cystatin C is associated with Mortality after Acute Respiratory Distress Syndrome: Findings from a Fluid and Catheter Treatment Trial (FACTT) Substudy

Hendrickson

Kwong

Belzer

et al. 2020

Preprint

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Background: Cystatin C is a well validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous critically-ill populations and may be superior to creatinine in identifying kidney injury in critically-ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with Acute Respiratory Distress Syndrome (ARDS) would be associated with mortality. Methods: In a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by Acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results : Cystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9 – 1.9) mg/L vs. 0.8 (0.6 – 1.2) mg/L, p <0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2-2.6), p =0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0-2.4), p =0.048] and those without AKI [OR 2.4 (1.2-5.0), p =0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality. Conclusions : Higher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60-days in patients with ARDS with and without AKI identified by creatinine-based definitions . Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.

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Evaluation of clinically available renal biomarkers in critically ill adults: a prospective multicenter observational study

Cited by 41 publications

References 49 publications

Proteomics and Metabolomics for AKI Diagnosis

Proteomics and Metabolomics for AKI Diagnosis

Dysbiosis of intestinal microbiota to predict in-hospital mortality in critically ill patients: results of a prospective observational cohort study

Higher Plasma Cystatin C is associated with Mortality after Acute Respiratory Distress Syndrome: Findings from a Fluid and Catheter Treatment Trial (FACTT) Substudy

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