Serum NGAL and copeptin levels as predictors of acute kidney injury in asphyxiated neonates

Background

Acute kidney injury (AKI) is the most common complication of perinatal asphyxia. Recent research indicates that serum neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI, but there are the lacks of data about its use in term neonates with perinatal asphyxia.

Methods

A prospective cohort study was conducted on 43 term neonates. Umbilical cord blood and 24 h after birth serum NGAL, copeptin, creatinine, and molality were measured in all asphyxiated and controls neonates.

Results

During the study period, 8 of asphyxiated nenates (18.6 %) suffered from AKI, while 35 newborns have no signs of AKI and 30 healthy infants. We did not observe any differences in creatinine and copeptin levels, as well as serum osmolality in all three investigated groups (AKI, no-AKI, and controls) in cord blood, and 24 h after birth. Serum NGAL levels in umbilical cord blood were significantly higher in the AKI group (174.3 ng/mL) compared with no-AKI (88.5 ng/mL, p = 0.01) and control groups (28.5 ng/mL, p < 0.001), and 24 h after birth (respectively, AKI 152.5 ng/mL vs no-AKI 74.9 ng/mL, p = 0.02 vs controls 39.1 ng/mL, p < 0.001). NGAL concentration showed a strong negative correlation to umbilical artery pH (Rho = ?0.42, p = 0.04), base excess (Rho = ?0.31, p = 0.03), and Apgar score in 1st min (Rho = ?0.41, p = 0.02) and 5th min of life (Rho = ?0.20, p = 0.001). ROC curve analysis demonstrated a good predictive value for NGAL levels (>140.7 ng/mL) which allows to diagnose AKI in asphyxiated patients with 88.9 % sensitivity (95 % CI 75–95 %) and 95.0 % specificity (95 % CI 76–99 %).

Conclusion

NGAL seems to be a promising marker, even in subclinical AKI in neonates, due to its high specificity, but copeptin did not meet expectations.

     

Some biomarkers of acute kidney injury are increased in pre-renal acute injury

Pre-renal acute kidney injury (AKI) is assumed to represent a physiological response to underperfusion. Its diagnosis is retrospective after a transient rise in plasma creatinine, usually associated with evidence of altered tubular transport, particularly that of sodium. In order to test whether pre-renal AKI is reversible because injury is less severe than that of sustained AKI, we measured urinary biomarkers of injury (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyl transpeptidase, IL-18, and kidney injury molecule-1 (KIM-1)) at 0, 12, and 24?h following ICU admission. A total of 529 patients were stratified into groups having no AKI, AKI with recovery by 24?h, recovery by 48?h, or the composite of AKI greater than 48?h or dialysis. Pre-renal AKI was identified in 61 patients as acute injury with recovery within 48?h and a fractional sodium excretion <1%. Biomarker concentrations significantly and progressively increased with the duration of AKI. After restricting the AKI recovery within the 48?h cohort to pre-renal AKI, this increase remained significant. The median concentration of KIM-1, cystatin C, and IL-18 were significantly greater in pre-renal AKI compared with no-AKI, while NGAL and γ-glutamyl transpeptidase concentrations were not significant. The median concentration of at least one biomarker was increased in all but three patients with pre-renal AKI. Thus, the reason why some but not all biomarkers were increased requires further study. The results suggest that pre-renal AKI represents a milder form of injury.     

Neutrophil gelatinase associated lipocalin as an indicator of acute kidney injury and inflammation in burned children

Introduction

Neutrophil gelatinase associated lipocalin (NGAL) is a novel predictor of acute kidney injury (AKI), which increases with inflammation. We aimed to assess whether serum NGAL (SNGAL) and urine NGAL (UNGAL) can predict AKI in burned children.

Methods

Patients were referred within the 12 h of burn to our center. Serum samples for SNGAL, C-reactive protein (CRP), procalcitonin (PCT) and urine for UNGAL, microalbumine (Umalb), creatinine (Ucr) were obtained at both admission and the 5th day after burn. Blood urea nitrogen (BUN) and serum creatinine (Scr) were examined daily.

Results

Twenty-two subjects were enrolled and six (27.2%) of them developed AKI within the 48 h of injury. Burn size and abbreviated burn severity index (ABSI) were significantly increased in patients with AKI. CRP, PCT, SNGAL and UNGAL levels at admission and day 5 were significantly higher in patients with AKI than in those without AKI and controls. Scr was not significant between AKI and non-AKI groups at hospital days 1 and 5. A SNGAL level of 315 ng/ml and a UNGAL level of 100 ng/ml were determined as predictive cut-off values of AKI at admission (sensitivity and specificity: 71.4%, 83.3% and 93.3%, 93.7%, respectively). SNGAL and UNGAL were positively correlated with CRP, PCT, ABSI and Umalb/Ucr.

Conclusion

SNGAL and UNGAL are good early predictors of AKI in children with severe burn. NGAL might reflect the severity of burn insult and also could be used as an indicator of inflammation in burn children.     

A combination of SOFA score and biomarkers gives a better prediction of septic AKI and in-hospital mortality in critically ill surgical patients: a pilot study

Background

Sepsis is a syndrome characterized by a constellation of clinical manifestations and a significantly high mortality rate in the surgical intensive care unit (ICU). It is frequently complicated by acute kidney injury (AKI), which, in turn, increases the risk of mortality. Therefore, it is of paramount importance to identify those septic patients at risk for the development of AKI and mortality. The objective of this pilot study was to evaluate several different biomarkers, including NGAL, calprotectin, KIM-1, cystatin C, and GDF-15, along with SOFA scores, in predicting the development of septic AKI and associated in-hospital mortality in critically ill surgical patients.

Methods

Patients admitted to the surgical ICU were prospectively enrolled, having given signed informed consent. Their blood and urine samples were obtained and subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of various novel biomarkers. The clinical data and survival outcome were recorded and analyzed.

Results

A total of 33 patients were enrolled in the study. Most patients received surgery prior to ICU admission, with abdominal surgery being the most common type of procedure (27 patients (81.8%)). In the study, 22 patients had a diagnosis of sepsis with varying degrees of AKI, while the remaining 11 were free of sepsis. Statistical analysis demonstrated that in patients with septic AKI versus those without, the following were significantly higher: serum NGAL (447.5?±?35.7 ng/mL vs. 256.5?±?31.8 ng/mL, P value 0.001), calprotectin (1030.3?±?298.6 pg/mL vs. 248.1?±?210.7 pg/mL, P value 0.049), urinary NGAL (434.2?±?31.5 ng/mL vs. 208.3?±?39.5 ng/mL, P value <?0.001), and SOFA score (11.5?±?1.2 vs. 4.4?±?0.5, P value <?0.001). On the other hand, serum NGAL (428.2?±?32.3 ng/mL vs. 300.4?±?44.3 ng/mL, P value 0.029) and urinary NGAL (422.3?±?33.7 ng/mL vs. 230.8?±?42.2 ng/mL, P value 0.001), together with SOFA scores (10.6?±?1.4 vs. 5.6?±?0.8, P value 0.003), were statistically higher in cases of in-hospital mortality. A combination of serum NGAL, urinary NGAL, and SOFA scores could predict in-hospital mortality with an AUROC of 0.911.

Conclusions

This pilot study demonstrated a promising panel that allows an early diagnosis, high sensitivity, and specificity and a prognostic value for septic AKI and in-hospital mortality in surgical ICU. Further study is warranted to validate our findings.

     

Assessment of fractional excretion of urea for early diagnosis of cardiac surgery associated acute kidney injury

Abstract

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine, but it is not widely used in clinical practice. Fractional excretion of urea (FeU) has been referred to as a useful tool to discriminate between prerenal and established AKI. The aim of our study is to evaluate the sensitivity and specificity of FeU, in the early diagnosis of AKI in patients undergoing CS. Methods: We performed a prospective study on adults undergoing CS. AKI was defined by AKIN criteria. Individuals suffering from CKD, were excluded. Sensitivity and specificity of FeU, fractional excretion of sodium (FeNa) and urine NGAL, measured at 1, 6 and 24?h following CS, were assessed. Results: We included 66 patients (26% female) aging 68?±?11 years. AKI prevalence was 24% and mortality was 3.28%. Patients with AKI had a significantly lower FeU compared to those without AKI (23.89?±?0.67% vs. 34.22?±?0.58%; p?<?0.05) 6?h after CS, but not at the 1- and 24-h time points. NGAL was also statistically significant between both groups. FeU showed a 75% sensitivity and 79.5% specificity; the AUC was 0.786. ROC analysis of FeU and NGAL yielded similar values (p?=?NS). Conclusion: FeU is useful as an early biomarker to predict AKI after CS and it is comparable to the new biomarker NGAL.     

Urinary markers of acute kidney injury in newborns with perinatal asphyxia*

Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA). Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria. Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p?<?0.001, p?<0.001, p <0.02, p <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p?=?0.002, p <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p?=?0.004) compared to those without AKI. Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients.     

Urine neutrophil gelatinase associated lipocalin as an early marker of acute kidney injury in hematopoietic stem cell transplantation patients

Abstract

Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation (HSCT) patients with an incidence of 21–73%. Prevention and early diagnosis reduces the frequency and severity of this complication. Predictive biomarkers are of major importance to timely diagnosis. Neutrophil gelatinase associated lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. We performed further analyses on gathered data from our recent trial to evaluate the performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT patients. AKI diagnosis and severity were assessed using Risk–Injury–Failure–Loss–End-stage renal disease and AKI Network criteria. We assessed uNGAL on days ?6, ?3, +3, +9 and +15. Time-dependant Cox regression analysis revealed a statistically significant relationship between uNGAL and AKI occurrence. (HR?=?1.04 (1.008–1.07), p?=?0.01). There was a relation between uNGAL day?+?9 to baseline ratio and incidence of AKI (unadjusted HR?=?1.047 (1.012–1.083), p?<?0.01). The area under the receiver-operating characteristic curve for day?+?9 to baseline ratio was 0.86 (0.74–0.99, p?<?0.01) and a cut-off value of 2.62 was 85% sensitive and 83% specific in predicting AKI. Our results indicated that increase in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations from baseline could be of value for predicting AKI in HSCT patients. Additionally uNGAL changes preceded serum Cr raises by nearly 2 days.     

Urinary MMP-9/NGAL complex in children with acute cystitis

The matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase associated lipocalin (NGAL) are shown to increase in an inflammatory situation. Based on our previous reports that NGAL can be detected in the urine of children with urinary tract infection (UTI), we also asked whether MMP-9/NGAL complex could be detected in the urine of children with UTI. This multicenter, prospective study was conducted between October 2009 and October 2010. Seventy-one patients with symptomatic culture proven UTI, 37 asymptomatic children with contaminated urine and 37 healthy children were recruited. Mean uMMP-9/NGAL/Cr levels were significantly higher in the UTI group than in the control group (p < 0.0001). According to ROC analysis, the optimal cut-off level was 0.08 ng/mg to predict UTI. Using a cut-off value, sensitivity and specificity were 98.6 and 97.3%, respectively. The mean levels of uMMP-9/NGAL/cr in the UTI group were also significantly higher than those in the contamination group (p < 0.0001). There was no statistically significant difference between contamination group and the control group (p = 0.21). The mean uMMP-9/NGAL/Cr in the UTI group were significantly higher before treatment than after treatment (p < 0.0001). The area under the curve was 0.997 (SE: 0.002, 95% CI: 0.993 to 1.001) for uMMP-9/NGAL/Cr. Urinary MMP-9/NGAL/Cr level was also correlated with positive urine nitrite test, positive urine leukocyte esterase reaction and renal scarring (p = 0.0001, p = 0.0001, p = 0.04, respectively) whereas was not correlated to leukocytosis and positive CRP level in serum. Urine MMP-9/NGAL/cr can be used as a diagnostic biomarker for UTI in children. Identification of NGAL-MMP-9/cr levels in the urine of suspected UTI patients may also be useful to differentiate between contamination and infection and for monitoring of treatment response in children.     

Admission hypomagnesemia and hypermagnesemia increase the risk of acute kidney injury

Abstract

Background: The association between admission serum magnesium (Mg) levels and risk of in-hospital acute kidney injury (AKI) is limited. The aim of this study was to assess the risk of developing AKI in all hospitalized patients with various admission Mg levels. Methods: This is a single-center retrospective study conducted at a tertiary referral hospital. All hospitalized adult patients who had admission Mg available from January to December 2013 were analyzed in this study. Admission Mg was categorized based on its distribution into six groups (less than 1.5, 1.5–1.7, 1.7–1.9, 1.9–2.1, 2.1–2.3 and greater than 2.3?mg/dL). The primary outcome was in-hospital AKI occurring after hospital admission. Logistic regression analysis was performed to obtain the odds ratio of AKI of various admission Mg levels using Mg with lowest AKI incidence (1.9–2.1?mg/dL) as the reference group. Results: Of 9241 patients enrolled, AKI occurred in 1124 patients (12.2%). The lowest incidence of AKI was when serum Mg was within 1.7–1.9 and 1.9–2.1?mg/dL. A U-shaped curve emerged demonstrating higher incidences of AKI associated with both hypoMg (<1.7) and hyperMg (>2.1). After adjusting for potential confounders, both hypoMg (<1.5?mg/dL) and hyperMg (>2.3?mg/dL) were associated with an increased risk of developing AKI with odds ratios of 1.70 (95% CI 1.31–2.18) and 1.42 (95% CI 1.11–1.81), respectively. Conclusion: Both admission hypoMg and hyperMg were associated with an increased risk for in-hospital AKI.     

Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery

Aim: To test whether short‐term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury (AKI) in cardiac surgical patients. Methods: We conducted a double‐blind, randomized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI. Patients were randomized to atorvastatin (40 mg once daily for 4 days starting preoperatively) or identical placebo capsule. Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy. Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification (RIFLE R, I or F), change in urinary neutrophil gelatinase‐associated lipocalin (NGAL) concentration, requirement for renal replacement therapy, length of stay in intensive care, length of stay in hospital and hospital mortality. Results: Study groups were well matched. For each patient maximal increase in creatinine during the 5 days after surgery was assessed; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group (P = 0.62). RIFLE R or greater occurred in 26% of patients with atorvastatin and 32% with placebo (P = 0.65). Postoperatively urine NGAL changes were similar (median NGAL : creatinine ratio at intensive care unit admission: atorvastatin group 1503 ng/mg, placebo group 1101 ng/mg; P = 0.22). Treatment was well tolerated and adverse events were similar between groups. Conclusion: Short‐term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL. (ClinicalTrials.gov NCT00910221).     

Diuretics associated acute kidney injury: clinical and pathological analysis

Objective: In order to evaluate the clinical and pathological characteristics of diuretics associated acute kidney injury (AKI) and its management. Methods: We performed a retrospective study including 131 cases that diagnosed as diuretics associated AKI from 1 January 1999 to 1 January 2010 in Ruijin Hospital affiliated to Shanghai Jiao Tong University. Drug applications and its related clinical, laboratory and histological data were collected. Results: The male to female ratio was 2:1. The proportion of ages <20 years, 20–40 years, 40–60 years and ≥60 years were 6.9%, 17.6%, 27.5% and 48.1% respectively. Most patients (96.2%) had at least one complication of which chronic kidney disease (CKD) occurred most frequently (72 in 131, 55.0%). We divided all the patients to diuretic group (N?=?131) and non-diuretic group (N?=?185) based on diuretics history. We found patients in diuretic group had higher rates of CVD (38.9% vs. 18.4%), hypertension (42.0% vs. 29.2%), CKD (55.0% vs. 27.0%) and DM (17.6% vs. 4.3%) than non-diuretic group. Of 131 diuretics associated AKI, 36 cases (27.5%) were caused by diuretics only, 39 cases (29.8%) were caused by the combination of diuretics and other drugs like antibiotics, contrast media, ACEI or NSAIDs, and 56 cases (42.7%) had other AKI risk factors such as operation, infection, acute heart failure or hepatorenal syndrome. In addition, our data suggested the severity of RIFLE classification and pathological injury of glomerular basement membrane was higher in large-dosage furosemide group (>?=?120?mg/d) than in low-dosage group (<120?mg/d). The most common lesion induced by diuretics was vacuolar degeneration of tubular epithelial cell. Logistic regression analysis showed predictors of all-cause mortality were age, gender, RIFLE classification when AKI onset. Age and RIFLE classification were predictive factor of non-complete recovery. Conclusion: This article firstly focuses on diuretics associated AKI, whose onset was related to aging, primary diseases and diuretic dosage. The combination of diuretics with other drugs such as antibiotics, contrast media, ACEI, NSAIDs, etc. would synergistically induced AKI. The pathological lesion of diuretics associated AKI may be mostly manifested vacuolar degeneration of tubular epithelial cell. Aging, gender, severity of RIFLE classification may be predictive factors of all-cause mortality of diuretics associated AKI.     

The efficacy of theophylline in preventing cisplatin-related nephrotoxicity in patients with cancer

Objective: Cisplatin is a potent antineoplastic agent used and its major limiting side effect is nephrotoxicity. The aims of the study are early detection of acute kidney injury (AKI) with biomarkers and investigation of the potential nephron-protective effects of theophylline. Methods: Glomerular filtration rates (GFR), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C were measured at 5th day of treatment in all of the patients. In addition, these parameters were measured repeatedly after the administration of cisplatin, at 2nd hour, 5th and 20th days. Patients: Sixty patients who are planned to receive cisplatin for the first time were included in the study. Patients were divided into two groups as Group 1 (n?=?30) (standard treatment arm) and Group II (n?=?30) (theophylline arm). Results: In both groups after the administration of cisplatin, GFR showed a significant decrease within time (p?=?0.006). Urine NGAL levels were significantly high after 2?h of cisplatin administration (p?p?=?0.025). After 5 days of cisplatin administration, urine protein levels were significantly higher in both groups (p?Conclusion: Results showed that urine NGAL level is a superior biomarker compared to serum creatinine and serum cystatin C in the detection of early AKI. Theophylline was found not to bring a complete protection for the kidneys, but less nephrotoxicity was developed when compared to the group not receiving theophylline.     

A pilot study of urinary fibroblast growth factor-2 and epithelial growth factor as potential biomarkers of acute kidney injury in critically ill children

Background

Acute kidney injury (AKI) increases the morbidity of critically ill children. Thus, it is necessary to identify better renal biomarkers to follow the outcome of these patients. This prospective case–control study explored the clinical value of a urinary biomarker profile comprised of neutrophil gelatinase lipocalin (uNGAL), fibroblast growth factor-2 (uFGF-2), and epidermal growth factor (uEGF) to follow these patients.

Methods

Urine samples were collected from 21 healthy children, and 39 critically ill children (mean age 7.5 years?±?6.97 SD) admitted to a pediatric intensive care unit with sepsis or requiring extra corporeal membrane oxygenation (ECMO). uNGAL, uFGF-2, and uEGF levels were measured using ELISA kits during the first 24 h of admission to PICU, at peak of illness, and upon resolution of the critical illness.

Results

On admission, the uNGAL and uFGF-2 levels were increased, and the uEGF levels were decreased, in critically ill children with AKI (n?=?19) compared to those without AKI (n?=?20), and healthy controls. A biomarker score using the combined cut-off values of uNGAL, uFGF-2, and uEGF (AUC?=?0.90) showed the highest specificity to identify children with AKI, relative to each biomarker alone. uNGAL and uFGF-2 on admission showed high sensitivity and specificity to predict mortality (AUC?=?0.82).

Conclusions

The biomarker profile comprised of uNGAL, uFGF-2, and uEGF increased the specificity to detect AKI in critically ill children, when compared to each biomarker used alone. uNGAL and uFGF-2 may also predict the risk of death. Further validation of these findings in a large sample size is warranted.     

Urine Neutrophil Gelatinase-Associated Lipocalin and Interleukin-18 Predict Acute Kidney Injury after Cardiac Surgery

Background. About 30–50% patients develop acute kidney injury (AKI) after cardiac surgery, which is still diagnosed by serum creatinine on clinic. However, the increase of serum creatinine is insensitive and delayed. The aim of this study is to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are early biomarkers for AKI in patients after cardiac surgery. Methods. Thirty-three cases undergoing cardiac surgery were classified into an AKI group and non-AKI group, according to the AKI definition (> 26.5 μmol/L increase of serum creatinine, more than or equal to 50% increase of serum creatinine within 48 h, or a reduction in urine output < 0.5 mL/Kg per hour for more than six hours). The concentrations of serum NGAL, urine NGAL, and urine IL-18 at different time-points were measured. Results. Nine cases (27.27%) developed postoperative AKI, but diagnosis with serum creatinine was 12–48 h postoperation. The concentrations of serum NGAL were not significantly increased postoperation. The concentrations of urine NGAL and IL-18 were significantly increased in the AKI group, which reached the peak at 2–4 h postoperation, and a more significant difference could be seen after correction for urine creatinine. The concentrations of urine NGAL and IL-18 2 h postoperation, either corrected for urine creatinine or not, showed good sensitivity and specificity. Increased levels of urine NGAL and IL-18 2 h postoperation were significantly correlated with increased level of serum creatinine 12 h postoperation. Logistic regression analysis showed that urine NGAL corrected for urine creatinine 2 h postoperation and urine IL-18 2 h postoperation emerged as powerful independent predictors of AKI after cardiac surgery. Conclusions. The concentrations of urine NGAL and IL-18 could be useful biomarkers for AKI in patients after cardiac surgery, especially after correction for urine creatinine.     

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

Abstract

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24?h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC?=?0.75), lower urine Hepcidin:Creatine ratio at 24?h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24?h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24?h?+?post-operative π-GST (AUC?=?0.86, p?=?0.01), Hepcidin:Cr 24?h?+?NGAL:Cr post-op (0.84, p?=?0.03) and CysC 24?h?+?post-operative π-GST (0.83, p?=?0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver–operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24?h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.     

尿中性粒细胞明胶酶相关载脂蛋白和肝型脂肪酸结合蛋白对肝移植术后急性肾损伤的早期诊断价值

目的 探讨尿中性粒细胞明胶酶相关载脂蛋白（NGAL）和肝型脂肪酸结合蛋白（L-FABP）在肝移植术后急性肾损伤（AKI）中的早期诊断价值。 方法 前瞻性收集2007至2008年间25例肝移植患者术前、门静脉开放后2、4、6、12、24、48、72和120 h的血液和尿液标本,检测Scr和尿NGAL及L-FABP水平。根据急性肾损伤网（AKIN）标准中的Scr标准将患者分为AKI组和非AKI组。观察两组各时间点尿NGAL、尿L-FABP和Scr水平的动态变化;运用受试者工作特征曲线（ROC）评价尿NGAL和L-FABP诊断AKI的精确性。 结果 25例患者中11例发生了术后AKI,两组患者术前、术中及术后情况差异无统计学意义。术后24 h AKI组与非AKI组的Scr差异有统计学意义[(90.48±50.32) 比（59.84±14.72） μmol/L,P < 0.05]。AKI组与非AKI组术后2～120 h尿L-FABP均显著升高,4 h时差异有统计学意义[2361.41（1036.89~4048.93） ng/mgCr比5246.97（2406.33~7688.21） ng/mgCr,P < 0.05]。AKI组术后2、4、6 h尿NGAL均显著高于非AKI组,差异有统计学意义 [69.02（29.79~237.29）比22.94（8.69~46.23） ng/mgCr,29.34（16.06~536.91）比 12.66（8.91~22.78） ng/mgCr和34.23（11.47~81.26）比11.84（6.57~20.10） ng/mgCr,均P < 0.05]。ROC曲线下面积（AUC）结果显示,与尿L-FABP相比（当4 h截断点为3451.75 ng/mgCr时,AUC为0.760）,尿NGAL对早期诊断AKI具有更高的敏感性和特异性（2、4、6 h的截断点分别为43.02、26.97和17.19 ng/mgCr时,AUC分别为0.766、0.773和0.773）。 结论 尿NGAL在肝移植术后早期AKI的诊断上表现出较高的敏感性和特异性,也许能作为肝移植术后AKI早期诊断的生物学标志物,但仍需要大样本的临床研究加以证实。     

Value of levels of biomarkers at the time of nephrologists consultation in predicting the prognosis of acute kidney injury patients

Objective To investigate the value of biomarker levels at the time of nephrologists consultation in predicting the prognosis of acute kidney injury (AKI) patients. Methods A total of 103 hospitalized patients with AKI were enrolled at the time of nephrologists consultation. Blood and urine samples were collected when patients were diagnosed as AKI. ELISA was used to detect the concentration of urinary biomarkers including neutrophil gelatinase?associated lipocalin (NGAL), IL?6 and IL?18. Colorimetric method was used to measure urinary N?acetyl?β?D?glucosaminidase (NAG). Turbidimetry and enzymic method were applied to examine the concentration of serum cystatin C (Cys C), baseline Scr (bScr), Scr at consultation (cScr) and the peak of Scr (pScr) respectively. Patients were followed?up to evaluate the prognosis at 28 days after consultation, including patient survival and kidney survival. The levels of biomarkers between different groups, including patient survival or death, kidney recovery or lose and renal replacement therapy (RRT) or not, were compared. Area under curve (AUC) of receiver operating characteristic (ROC) curve of these biomarkers were used to evaluate the sensitivity and specificity in predicting prognosis. AKI was defined as the Scr at the time of consultation increased more than 50% of baseline Scr within 48 hours. Results (1)Mean age of 103 hospitalized AKI patients was (54.28±19.05) years old and ratio of male to female was 1.86 to 1. (2)Patient mortality was 25.2% at 28 days after consultation. The bScr, cScr and pScr were similar between survival and death group, while the concentration of urinary NGAL in death group was significantly higher than that of survival group [147.00(31.59, 221.87) mg/L vs 22.43(6.48, 89.77) mg/L, P＝0.001]. The serum Cys C, urinary IL?6 and NAG were similar between survival and death group (P＞0.05). Logistic regression analysis showed urinary NGAL was an independent risk factor of patient survival (OR＝1.011, 95%CI 1.004?1.018, P＝0.001) with AUC of 0.723. (3)Kidney lose rate was 20.4% at 28 days after consultation. The bScr, cScr and pScr were similar between patients with kidney survival and lose. The levels of urinary NAG, IL?6, NGAL and IL?18 were significantly higher in patients with kidney lose than those of kidney survival. Logistic regression analysis showed urinary IL?6 was an independent risk factor of renal survival (OR＝1.056, 95%CI 1.009?1.105, P＝0.018) with AUC of 0.705. (4)The median time from consultation to RRT was 2.17 (0?3) days. The concentrations of cScr, pScr, serum Cys C, urinary IL?6 and NGAL were significantly higher in RRT patients than thosein non?RRT patients (P＜0.05). Logistic regression analysis showed urinary NGAL was an independent risk factor of RRT (OR＝1.012, 95%CI 1.005?1.019, P＜0.01) with AUC of 0.775. Conclusions Urinary NGAL can predict the prognosis of AKI patients, including patient prognosis and RRT. Urinary IL?6 may predict kidney prognosis in hospitalized patients with AKI. More study with large samples should be done for further estimation of the results.     

Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery.     

Creatinine,Neutrophil Gelatinase‐Associated Lipocalin,and Cystatin C in Determining Acute Kidney Injury After Heart Operations Using Cardiopulmonary Bypass

Acute kidney injury (AKI) represents frequent complication after cardiac surgery using cardiopulmonary bypass (CPB). In the hope to enhance earlier more reliable characterization of AKI, we tested the utility of neutrophil gelatinase‐associated lipocalin (NGAL) and cystatin C (CysC) in addition to standard creatinine for early determination of AKI after cardiac surgery using CPB. Forty‐one patients met the inclusion criteria. Arterial blood samples collected after induction of general anesthesia were used as baseline, further sampling occurred at CPB termination, 2 h after CPB, on the first and second day after surgery. According to AKIN classification 18 patients (44%) developed AKI (AKI1‐2 groups) and 23 (56%) did not (non‐AKI group). Groups were similar regarding demographics and operative characteristics. CysC levels differed already preoperatively (non‐AKI vs. AKI2; P = 0.045; AKI1 vs. AKI2; P = 0.011), while postoperatively AKI2 group differed on the first day and AKI1 on the second regarding non‐AKI group (P = 0.004; P = 0.021, respectively). NGAL and creatinine showed significant difference already 2 h after CPB between groups AKI2 and non‐AKI and later on the first postoperative day between groups AKI1 and AKI2 (P = 0.028; P = 0.014, respectively). This study shows similar performance of early plasma creatinine and NGAL in patients with preserved preoperative renal function. It demonstrates that creatinine, as well as NGAL, differentiate subsets of patients developing AKI of clinically more advanced grade early after 2 h, also when used single and uncombined.     

Urine neutrophil gelatinase-associated lipocalin to predict acute kidney injury in preterm neonates. A pilot study

Background

The efficacy of urine neutrophil gelatinase-associated lipocalin (uNGAL) as an early acute kidney injury (AKI) biomarker in preterm neonates was evaluated.

Methods

Thirty-five preterm neonates were prospectively evaluated for serum creatinine (sCre)-documented AKI during the first 14 days of life. Urine samples were collected daily throughout the study period. Of the neonates evaluated, we analyzed 11 who developed AKI (cases) and an equal number of neonates without AKI (controls) matched for gestational and postnatal age (case–control study). uNGAL was measured on the day of AKI occurrence (day 0) and on the 2 days preceding the event (day ?1 and day ?2, respectively) using an enzyme-linked immunosorbent assay.

Results

Cases had significantly higher sCre levels than controls on day 0 (1.21?±?0.48 vs. 0.83?±?0.16 mg/dL, p?=?0.031) but not on days ?1 and ?2. Similarly, uNGAL levels (ng/mL) were significantly higher in cases than in controls only on day 0 (19.1?±?3.5 vs. 13.3?±?7.3, p?=?0.017) and not on days ?1 (18.8?±?3.4 vs. 16.3?±?5.9, p?=?0.118) and ?2 (19.3?±?1.8 vs. 19.4?±?0.8, p?=?0.979). The receiver operating characteristic curve analysis showed no significant ability of uNGAL to predict AKI on days ?2 and ?1.

Conclusions

In this pilot study in preterm neonates, although uNGAL detected sCre-based AKI upon its documentation, it failed to predict its development 1–2 days earlier.