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      • KCI등재

        Predictive Value of Plasma NGAL:Hepcidin-25 for Major Adverse Kidney Events After Cardiac Surgery with Cardiopulmonary Bypass: A Pilot Study

        Albert Christian,Haase Michael,Albert Annemarie,Ernst Martin,Kropf Siegfried,Bellomo Rinaldo,Westphal Sabine,Braun-Dullaeus Rüdiger C.,Haase-Fielitz Anja,Elitok Saban 대한진단검사의학회 2021 Annals of Laboratory Medicine Vol.41 No.4

        Background: Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery. Methods: We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI >48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses. Results: At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC <0.70). Only plasma NGAL:hepcidin-25 correctly reclassified patients according to their MAKE and AKI status (category-free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25 ≥0.9 independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P=0.014). Conclusions: Plasma NGAL:hepcidin-25 is a promising marker for predicting postoperative MAKE.

      • KCI등재

        Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation?

        Albert Christian,Haase Michael,Albert Annemarie,Zapf Antonia,Braun-Dullaeus Rüdiger Christian,Haase-Fielitz Anja 대한진단검사의학회 2021 Annals of Laboratory Medicine Vol.41 No.1

        Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis. In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as “preclinical-” and “subclinical AKI” have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

      • KCI등재

        Neutrophil Gelatinase-Associated Lipocalin Cutoff Value Selection and Acute Kidney Injury Classification System Determine Phenotype Allocation and Associated Outcomes

        Albert Annemarie,Radtke Sebastian,Blume Louisa,Bellomo Rinaldo,Haase Michael,Stieger Philipp,Hinkel Ulrich Paul,Braun-Dullaeus Rüdiger C.,Albert Christian 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.6

        Background: We explored the extent to which neutrophil gelatinase-associated lipocalin (NGAL) cutoff value selection and the acute kidney injury (AKI) classification system determine clinical AKI-phenotype allocation and associated outcomes. Methods: Cutoff values from ROC curves of data from two independent prospective cardiac surgery study cohorts (Magdeburg and Berlin, Germany) were used to predict Kidney Disease: Improving Global Outcome (KDIGO)- or Risk, Injury, Failure, Loss of kidney function, End-stage (RIFLE)-defined AKI. Statistical methodologies (maximum Youden index, lowest distance to [0, 1] in ROC space, sensitivity≈specificity) and cutoff values from two NGAL meta-analyses were evaluated. Associated risks of adverse outcomes (acute dialysis initiation and in-hospital mortality) were compared. Results: NGAL cutoff concentrations calculated from ROC curves to predict AKI varied according to the statistical methodology and AKI classification system (10.6–159.1 and 16.85–149.3 ng/mL in the Magdeburg and Berlin cohorts, respectively). Proportions of attributed subclinical AKI ranged 2%–33.0% and 10.1%–33.1% in the Magdeburg and Berlin cohorts, respectively. The difference in calculated risk for adverse outcomes (fraction of odds ratios for AKI-phenotype group differences) varied considerably when changing the cutoff concentration within the RIFLE or KDIGO classification (up to 18.33- and 16.11-times risk difference, respectively) and was even greater when comparing cutoff methodologies between RIFLE and KDIGO classifications (up to 25.7-times risk difference). Conclusions: NGAL positivity adds prognostic information regardless of RIFLE or KDIGO classification or cutoff selection methodology. The risk of adverse events depends on the methodology of cutoff selection and AKI classification system.

      • KCI등재

        Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study

        Christian Albert,Michael Haase,Annemarie Albert,Siegfried Kropf,Rinaldo Bellomo,Sabine Westphal,Mark Westerman,Rüdiger Christian Braun-Dullaeus,Anja Haase-Fielitz 대한진단검사의학회 2020 Annals of Laboratory Medicine Vol.40 No.2

        Background: The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events. Methods: This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement. Results: NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01–1.14]), Interleukin-6 (1.51 [1.01–2.26]), midkine (1.01 [1.00–1.02]), 1-hepcidin-25 (1.08 [1.00–1.17]), and NGAL/hepcidin-ratio (2.91 [1.30–6.49]) were independent predictors of MAKE and AKI (1.38 [1.03–1.85], 1.08 [1.01–1.15], 1.01 [1.00–1.02], 1.09 [1.01–1.18], and 3.45 [1.54–7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI. Conclusions: NGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The com

      • KCI등재

        Integration and Reanalysis of Four RNA-Seq Datasets Including BALF, Nasopharyngeal Swabs, Lung Biopsy, and Mouse Models Reveals Common Immune Features of COVID-19

        Alberts Rudi,Chan Sze Chun,Meng Qian-Fang,He Shan,Rao Lang,Liu Xindong,Zhang Yongliang 대한면역학회 2022 Immune Network Vol.22 No.3

        Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

      • KCI등재

        Epidemiology of PAH in Korea: An Analysis of the National Health Insurance Data, 2002–2018

        Albert Youngwoo Jang,Hyeok-Hee Lee,Hokyou Lee,Hyeon Chang Kim,Wook-Jin Chung 대한심장학회 2023 Korean Circulation Journal Vol.53 No.5

        Background and Objectives: Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Recent advances in PAH-specific drugs have improved its outcomes, although the healthcare burden of novel therapeutics may lead to a discrepancy in outcomes between developing and developed countries. We analyzed how the epidemiology and clinical features of PAH has changed through the rapidly advancing healthcare infrastructure in South Korea. Methods: PAH was defined according to a newly devised 3-component algorithm. Using a nationwide health insurance claims database, we delineated annual trends in the prevalence, incidence, medication prescription pattern, and 5-year survival of PAH in Korea. Cumulative survival and potential predictors of mortality were also assessed among 2,151 incident PAH cases. Results: Between 2002 or 2004 and 2018, the prevalence and incidence of PAH increased 75-fold (0.4 to 29.9 per million people) and 12-fold (0.5 to 6.3 per million person-years), respectively. The proportion of patients on combination PAH-specific drug therapy has also steadily increased up to 29.0% in 2018. Among 2,151 incident PAH cases (median [interquartile range] age, 50 [37–62] years; 67.2% female), the 5-year survival rate and median survival duration were 71.8% and 13.1 years, respectively. Independent predictors of mortality were age, sex, etiology of PAH, diabetes, dyslipidemia, and chronic kidney disease. Conclusions: This nationwide study delineated that the prevalence and incidence of PAH have grown rapidly in Korea since the early 2000s. The use of combination therapy has also increased, and the 5-year survival rate of PAH in Korea was similar to those in western countries.

      • KCI등재

        From Cakravartin Ideal to Realpolitik: Zanning and the Accommodation of Chinese Buddhism to Neo-Confucianism

        ( Albert Welter ) 한국유교학회 2011 유교사상문화연구 Vol.44 No.-

        轉法輪王의 이상으로부터 현실정치까지-贊寧과 중국불교의 程朱理學과 습합 송나라에서 신유학의 발흥은 중국불교의 입장에서는 새로운 도전이었다. 본 논문에서 필자는 불교역사학자이자 문인인 贊寧 (919-1001)이 제시한 불교와 세속적인 정치, 소위 현실정치와의 통합적인 모델을 제시하려고 한다. 찬녕의 실천과는 달리 전통적으로 불교는 불법의 바퀴를 돌린다는 의미의 轉法輪王의 이상을 가지고 있었다. 본 논문은 불교와 현실정치, 특히 유교국가의 통합에 대한 큰 그림을 그리고 현대 불교의 가능성을 보고자 한다. The rise of Neo-Confucianism in the Song dynasty presented new challenges for Buddhism in China. In this presentation, I discuss the model proposed by the Buddhist historian and literatus Zanning 贊寧 (919-1001) for the integration of Buddhism into the Confucian secular state in terms of realpolitik 現實政治, contrasting it with the traditional Buddhist model of a Dharma-Wheel turning monarch, the cakravartin 轉法輪王. The presentation is framed within larger concerns relating to the integration and accommodation of Buddhism into a Confucian state, and its implications for contemporary China.

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