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      The Level of the Biomarkers at the Time of Nephrology Consultation Might Predict the Prognosis of Acute Kidney Injury in Hospitalized Patients

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          Introduction: The value of biomarkers at the time of nephrology consultation in predicting the prognosis of acute kidney injury (AKI) in hospitalized patients has not been well described. This study aimed to evaluate the possibility of biomarkers at the time of nephrology consultation in predicting the prognosis of AKI. Methods: We prospectively enrolled 103 hospitalized patients who developed AKI. Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL), IL-6, IL-18, N-Acetyl-F-D-Glucosaminidase (NAG), and serum Cystatin C (CysC) were measured at the time of nephrology consultation. Baseline values of serum creatinine (bScr), serum creatinine on consultation (cScr) and the peak level of serum creatinine (pScr) were recorded. All the patients were followed-up till 28 days since consultation. Serum and urinary levels of the biomarkers were compared according to the patient or kidney prognosis. Each marker was assessed for its predictive value using receiver operator characteristic (ROC) curves to predict AKI prognosis. Results: Patients were aged 54.28 w 19.05. Male patients constituted 65% of the study group and baseline Scr was 93.54 w 35.98 Vmol/l. The mortality rate of the patients was 25.2% and kidney loss rate was 18.8% at 28 days after consultation. The level of urinary NGAL was significantly higher in death patients than that in survival patients [147.00 (31.59, 221.87) Vg/ml vs. 22.43 (6.48, 89.77) Vg/ml, p = 0.001], while the level of bScr, cScr, pScr, urinary IL-6 and NAG were similar in both these groups. The AUC of urinary NGAL for predicting patients' death was 0.723 (p = 0.001). Serum CysC and urinary IL-18 concentration was higher in the death patients with a marginal p value (p = 0.065 and 0.059 respectively). All the urinary markers, including NAG, NGAL, IL-6 and IL-18 were significantly higher in patients with kidney loss than in those with kidney survival, while no difference was found in Scr and serum CysC levels. The AUCs of these urinary biomarkers for predicting kidney survival were 0.663, 0.655, 0.705 and 0.663 respectively (p < 0.05). The concentrations of cScr, pScr, serum CysC, urinary IL-6 and NGAL were significantly higher in RRT patients (p < 0.05). The AUCs for predicting RRT were 0.628, 0.781, 0.768, 0.672 and 0.775 respectively. Conclusions: The level of biomarkers at the time of nephrology consultation might predict the prognosis of AKI in hospitalized patients. Further studies should be done to understand the role of the serum and urinary markers in the prognosis of AKI. i 2014 S. Karger AG, Basel

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          Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.

          The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.
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            Is Open Access

            Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study

            Introduction Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers has impaired our ability to intervene in a timely manner. We previously showed in a small cohort of patients that plasma neutrophil gelatinase-associated lipocalin (NGAL), measured using a research enzyme-linked immunosorbent assay, is an early predictive biomarker of AKI after CPB. In this study we tested whether a point-of-care NGAL device can predict AKI after CPB in a larger cohort. Methods First, in a cross-sectional pilot study including 40 plasma samples (NGAL range 60 to 730 ng/ml) and 12 calibration standards (NGAL range 0 to 1,925 ng/ml), NGAL measurements by enzyme-linked immunosorbent assay and by Triage® NGAL Device (Biosite Inc., San Diego, CA, USA) were highly correlated (r = 0.94). Second, in a subsequent prospective uncontrolled cohort study, 120 children undergoing CPB were enrolled. Plasma was collected at baseline and at frequent intervals for 24 hours after CPB, and analyzed for NGAL using the Triage® NGAL device. The primary outcome was AKI, which was defined as a 50% or greater increase in serum creatinine. Results AKI developed in 45 patients (37%), but the diagnosis using serum creatinine was delayed by 2 to 3 days after CPB. In contrast, mean plasma NGAL levels increased threefold within 2 hours of CPB and remained significantly elevated for the duration of the study. By multivariate analysis, plasma NGAL at 2 hours after CPB was the most powerful independent predictor of AKI (β = 0.004, P < 0.0001). For the 2-hour plasma NGAL measurement, the area under the curve was 0.96, sensitivity was 0.84, and specificity was 0.94 for prediction of AKI using a cut-off value of 150 ng/ml. The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine (r = 0.46, P < 0.001), duration of AKI (r = 0.57, P < 0.001), and length of hospital stay (r = 0.44, P < 0.001). The 12-hour plasma NGAL strongly correlated with mortality (r = 0.48, P = 0.004) and all measures of morbidity mentioned above. Conclusion Accurate measurements of plasma NGAL are obtained using the point-of-care Triage® NGAL device. Plasma NGAL is an early predictive biomarker of AKI, morbidity, and mortality after pediatric CPB.
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              Plasma cytokine levels predict mortality in patients with acute renal failure.

              Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF. The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness. When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients. There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                December 2014
                17 October 2014
                : 38
                : 2
                : 89-95
                Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
                Author notes
                *Yucheng Yan, Renal Division, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127 (China), E-Mail
                362865 Blood Purif 2014;38:89-95
                © 2014 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 4, Pages: 7
                Original Paper

                Cardiovascular Medicine, Nephrology

                IL-6, Acute kidney injury, NGAL, Prognosis, IL-18, NAG, Cystatin C


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