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.     

Urine neutrophil gelatinase-associated lipocalin in septic patients with and without acute kidney injury

Introduction: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a rapidly emerging biomarker for early detection of acute kidney injury (AKI). We aimed to investigate the prevalence and prognostic value of the early uNGAL in patients with AKI induced by sepsis. Methods: In this prospective cohort study, we analyzed the case records of 126 septic patients with and without AKI and evaluated the uNGAL for early prediction and risk stratification of septic patients with AKI. Results: Of 126 patients analyzed, 58 (46%) developed septic AKI. Men comprised more than half (68%) of the sample population, the mean age (SD) was 57 years. The prognostic accuracy of uNGAL, as quantified by the area under the receiver-operating-characteristic curve (AU-ROC), was highest with peak uNGAL (AU-ROC: 0.86; 95% CI: 0.81–0.93), as compared with the admission uNGAL (AU-ROC: 0.81; 95% CI: 0.73–0.89). The peak uNGAL correlated with the levels of peak blood urea nitrogen (r?=?0.674) and serum creatinine (r?=?0.608), the length of hospital stay (r?=?0.602) and weakly correlated with the number of hemodialysis sessions that each patient received during hospital stay (r?=?0.405). By multivariate analysis, increased peak uNGAL remained independently associated with the development of septic AKI (odds ratio: 32.12; 95% CI: 6.21–90.37; p?Conclusions: uNGAL is independently associated with subsequent AKI among patients with sepsis.     

Serum and urine acute kidney injury biomarkers in asphyxiated neonates

Background

We evaluated serum (s) cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) and urine (u) CysC, NGAL and kidney injury molecule-1 (KIM-1) as markers of acute kidney injury (AKI) in asphyxiated neonates.

Methods

AKI biomarkers were measured in 13 asphyxiated neonates born at ≥36?weeks gestational age (eight with AKI and five without AKI) and 22 controls. AKI was defined as serum creatinine ≥1.5?mg/dl for >24?h or rising values >0.3?mg/dl from day of life (DOL) 1. Biomarkers were measured on DOL 1, 3, and 10.

Results

Asphyxiated neonates had significantly higher sCysC on DOL 1 as well as sNGAL and uCysC and uNGAL (standardized to urine creatinine and absolute values) than controls at all time points. Compared to controls, significantly higher sNGAL, uCysC, and uNGAL values were observed in the asphyxia-AKI and asphyxia–no AKI subgroups. Regarding uKIM-1, only the absolute values were significantly higher in asphyxiated neonates (DOL 10). sNGAL, uCyst, and uNGAL had a significant diagnostic performance as predictors AKI on DOL 1.

Conclusions

sNGAL, uCysC, and uNGAL are sensitive, early AKI biomarkers, increasing significantly in asphyxiated neonates even in those not fulfilling AKI criteria. Their measurement on DOL 1 is predictive of post-asphyxia-AKI.     

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.     

Serum NGAL and FGF23 may have certain value in early diagnosis of CIN

Aims: This study aimed to assess whether neutrophil gelatinase-associated lipocalin (NGAL) and fibroblast growth factor 23 (FGF23) could be reliable biomarkers for early diagnosis of contrast-induced nephropathy (CIN).

Methods: 202 patients who underwent percutaneous coronary intervention (PCI) were included in the research. All subjects were divided into CIN group and non-CIN group. Serum NGAL and FGF23 were evaluated before and 0, 1, and 2 days after PCI. Serum levels of these two markers were compared intra-group and among groups. Receiver-operating characteristic (ROC) analysis and logistic regression models were conducted to assess the diagnostic performance of NGAL and FGF23 in detecting CIN.

Results: When compared with baseline values, serum levels of both NGAL and FGF23 in all subjects increased after PCI, and the values peaked 1?day after PCI, but the changing was greater in CIN group. There were obvious differences between two groups in serum NGAL after 1, 2 days, and similar differences present in serum FGF23 after 1?day. ROC analysis showed that the area under the curve (AUC) of relative values (percent change from the baseline) in NGAL after 1?day was 0.899 (95% CI: 0.834–0.964, p?=?.000), the optimum cutoff was 49% (sensitivity?=?80%, specificity?=?92.4%). And the AUC in FGF23 was 0.814 (95% CI: 0.733–0.894, p?=?.000), the optimum cutoff was 20% (sensitivity?=?73.3%, specificity?=?87.6%). Both serum NGAL and serum FGF23 could improve the clinical models in identifying CIN.

Conclusions: NGAL and FGF23 may have certain value in early diagnosis of CIN.     

Urine neutrophil gelatinase-associated lipocalin levels predict acute kidney injury in acute decompensated heart failure patients

Abstract

Background: Acute heart failure (HF) syndromes are frequently complicated with cardiorenal syndromes. The aim of this study was to evaluate the performance of admission neutrophil gelatinase associated lipocalin (NGAL) levels to predict diuretic dose requirement and to predict the occurrence of acute kidney injury (AKI) in patients presenting with acute decompensated HF. Methods: Patients admitted with HF symptoms between December 2010 and October 2011 were prospectively enrolled. Samples were obtained for NGAL and brain natriuretic peptide. Patients were followed up until discharge or for three days, whichever happened first. They were grouped either to have AKI according to “Acute Kidney Injury Network” criteria or not (“no-AKI”). Results: One hundred patients were enrolled. Urine NGAL levels were higher in AKI group (median 31.3 vs. 16.2 ng/mL) (p?<?0.001). Oral furosemide using rates on admission was 60.5% in AKI group, 31.6% in no-AKI group. More AKI developed in patients using less furosemide orally on admission (p?=?0.023). Although the mean furosemide doses were similar on the first day (80?mg), diuretic dose increment was less on the following days in AKI group. Urine NGAL levels with 12?ng/mL cut-off value had sensitivity of 79% and specificity of 67% for predicting AKI. Multiple logistic regression analysis yielded an odds ratio of 10.9 for NGAL levels to predict AKI. Conclusion: Urine NGAL level in decompensated HF patients was not a significant predictor of diuretic dose requirement, but was a good marker for predicting AKI at 12?ng/mL cut-off value.     

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.     

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.     

Combination of renal biomarkers predicts acute kidney injury in critically ill adults

Objective: Most studies so far have focused on the performance of individual biomarkers to detect early acute kidney injury (AKI) in the adult intensive care unit (ICU) patients; however, they have not determined the predictive ability of their combinations. The aim of this study was to compare the predictive abilities of plasma neutrophil gelatinase-associated lipocalin (pNGAL), urine neutrophil gelatinase-associated lipocalin (uNGAL), plasma cystatin C (pCysC), serum creatinine (sCr), and their combinations in detecting AKI in an adult general ICU population. Methods: A total of 100 consecutive ICU patients were included in the analysis. AKI was defined according to RIFLE criteria. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassi?cation improvement (NRI), and integrated discrimination improvement (IDI). Results: AKI occurred in 36% of patients 7 days post-admission. All three novel biomarkers as well as sCr had moderate predictive abilities for AKI occurrence. The most efficient combinations (pNGAL?+?sCr and pNGAL?+?uNGAL?+?sCr) were selected to participate in the subsequent analyses. Both combinations, when added to a reference clinical model, increased its AUC significantly (0.858, p?=?0.04). Their NRI (0.78, p?=?0.0002) was equal to that of pNGAL, but higher than that of the other three biomarkers, whereas their IDI was higher than that of any individual biomarker (0.23, p?=?0.0001). Both combinations had better specificities, positive likelihood ratios, and positive predictive values than those of any individual biomarker. Conclusion: The biomarker combinations had better predictive characteristics compared with those of each biomarker alone.     

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.     

Preoperative serum cystatin C combined with dipstick proteinuria predicts acute kidney injury after cardiac surgery

Background: Acute kidney injury (AKI) is common following cardiac surgery and is associated with poor outcomes. However, the detection of those preoperative patients who will develop AKI is still difficult. In this study, we compared serum cystatin C combined with dipstick proteinuria as early markers to predict AKI available before surgery. Methods: We prospectively followed 616 patients undergoing cardiac surgery and identified 179 that developed AKI, defined as an increase in serum creatinine (SCr) of ≥?0.3?mg/dL or ≥?50% increase in creatinine level. Preoperative values for cystatin C were categorized into quartiles. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2?+?to 4+). Univariate as well as multivariate regression was performed. Cystatin C combined with dipstick proteinuria before surgery was assessed for its' predictive value of AKI using receiver operating characteristic (ROC) curves. Results: The final cohort consisted of 616 patients aged 60.7?±?13.2 years, and baseline SCr was 75.8?±?26.4?μmol/L, estimated glomerular filtration rate (eGFR) 96.3?±?29.0?mL/min/1.73?m² and cystatin C 1.05?±?0.33?mg/L. Patients in higher cystatin C quartiles were older (p?p?=?0.021), hyperuricemia (p?p?p?=?0.002). Those with heavy proteinuria were more often to have diabetes mellitus (p?=?0.010), hyperuricemia (p?=?0.043), worse cardiac function (p?p?p?p?p?p?p?p?Conclusion: These data suggest that preoperative serum cystatin C combined with dipstick proteinuria may improve prediction of AKI among patients 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.     

Do neutrophil gelatinase-associated lipocalin and interleukin-18 predict renal dysfunction in patients with familial Mediterranean fever and amyloidosis?

Background: The aim of this study was to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) predict renal disfunction in patients with familial Mediterranean fever (FMF). Methods: This prospective study consisted of 102 patients with FMF in attack-free period, and 40 matched healthy controls. Of the patients, nine were diagnosed as amyloidosis. The patients were divided into two groups according to eGFR as below 120?mL per minute and above 120?mL per minute. Also, patients were divided into three groups according to the degree of urinary albumin excretion as normoalbuminuric, microalbuminuric, and macroalbuminuric. The serum levels of IL-18 (sIL-18) and NGAL (sNGAL), and urinary levels of IL-18 (uIL-18) and NGAL (uNGAL) were measured by using ELISA kits. Results: The levels of sIL-18, sNGAL, uIL-18, and uNGAL were detected significantly higher in FMF patients, particularly in patients with amyloidosis, when compared to controls. sNGAL, uIL-18, and uNGAL were significantly higher in patients with eGFR?Conclusions: The results of this study suggest that sIL-18, uIL-18, sNGAL, and uNGAL are reliable markers of early renal disfunction in FMF patients, and may let us take measures from the early stage of renal involvement.     

尿NGAL、NAG及KIM-1联合检测在高龄老年急性肾损伤早期诊断中的价值

目的探讨尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)、尿N-乙酰β-D氨基葡萄糖苷酶(uNAG)及尿肾损伤分子-1(uKIM-1)的联合检测老年急性肾损伤中的诊断价值。方法选择2016年6月至2018年6月在泰山疗养院住院的老年患者184例,根据急性肾损伤网络(AKIN)标准为诊断标准,诊断AKI组116例(1期55例、2期39例、3期24例),非AKI组68例,检测并比较各组尿NGAL、NAG、KIM-1水平,用受试者工作特征曲线(ROC)及曲线下面积(AUC)分析3项生物学标志物对AIK的诊断价值。结果①AKI组尿NGAL、NAG、KIM-1明显高于对照组(P<0.05),3期尿NGAL、NAG、KIM-1明显高于2期和1期,2期明显高于1期(P<0.05);②尿NGAL、NAG、KIM-1单独诊断AKI的AUC分别为0.734、0.804、0.705;③3项标志物联合诊断AKI的灵敏度、特异度分别为84.9%、90.7%,高于各单项诊断。结论尿NGAL、NAG、KIM-1是诊断AKI的较好指标,联合诊断对高龄老年急性肾损伤的早期诊断有着更重要的价值。     

Value of joint detection of multiple biomarkers on early diagnosis of acute kidney injury in critical patients

Objective To assess the value of joint detection of serum cysteine proteinase inhibitors C (sCys-C), urinary kidney injury molecule 1 (uKIM-1), urinary neutrophil gelatinase-associated lipocalin(uNGAL) and urinary interleukin 18 (uIL-18) for early diagnosis of acute kidney injury (AKI) in critically ill patients. Methods A total of 256 adult patients who stayed Intensive Care Unit for 24 hours in the Third People's Hospital of Liaocheng between Aug 2011 and Dec 2012 were enrolled. According to Kidney Injury Net(AKIN) work, the patients were divided into non-AKI group and AKI group (including state 1, 2 and 3). The concentrations of urine NGAL, KIM-1, IL-18 and serum sCys-C were measured. The diagnosis value of four biomarkers joint detection and single detection for AKI were analyzed with the receiver operating characteristic (ROC) curve and the area under curve (AUC). Results (1) The levels of uNGAL, uKIM-1, uIL-18 and sCys-C were higher in patients with AKI than the patients with no AKI (P﹤0.01). (2) The area under curves of uNGAL, uKIM-1, uIL-18, sCys-C and joint detection were 0.742, 0.871, 0.803, 0.703, 0.925 respectively. (3) The sensitivity and specificity of parallel tests and serial tests of four biomarkers were 97.9%, 62.8%, 64.3% and 96.2% respectively. There were significant differences of sensitivity or specificity between single test and joint tests. Conclusions The urine NGAL, KIM-1, IL-18 and serum Cys-C are sensitive indexes for the early diagnosis of acute kidney injury. Joint detection has high value for early diagnosis of AKI.     

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.     

Recurrent acute kidney injury in elderly patients is common and associated with 1-year mortality

Background

Acute kidney injury (AKI) is common among elderly patients after a first hospitalized AKI. Patients who recover are at risk for recurrence, but recurrent geriatric AKI is not well-studied.

Methods

This was a retrospective, 12-month cohort study using data from the National Clinical Research Center for Geriatric Diseases. Recurrent AKI was defined as a new spontaneous rise of?≥?0.3 mg/dl (≥?26.5 µmol/L) within 48 h or a 50% increase in serum creatinine (Scr) from the baseline within 7 days after the previous AKI episode. The outcome measured was 12-month mortality.

Results

Among 1711 study patients, 652 developed AKI. Of the 429 AKI survivors in whom recovery could be assessed, 314 patients recovered to their baseline renal function, and 115 patients developed chronic kidney disease (CKD). Of the group that recovered renal function, 90 patients (28.7%) subsequently developed recurrent AKI, while 224 (71.3%) did not. Of the 429 survivors with AKI, 103 patients (24.0%) died within 12 months. Multivariate logistic regression analysis revealed that recurrent AKI was significantly associated with coronary disease (odds ratio [OR?=?2.008; 95% confidence interval [CI] 1.024–3.938; P?=?0.042), a need for mechanical ventilation (OR?=?2.265; 95% CI 1.267–4.051; P?=?0.006) and high blood urea nitrogen levels (OR?=?1.036; 95% CI 1.002–1.072; P?=?0.040) at the first AKI event. Kaplan–Meier curves showed the 12-month survival of patients with non-recurrent AKI was better than that of patients with CKD, and survival of patients with recurrent AKI was worse than that of patients with CKD (log rank P?<?0.001). In the multivariate Cox regression analysis, mortality at 12 month was higher in the patient with recurrent AKI as compared with those with a single episode (HR?=?3.375; 95% CI 2.241–5.083; P?<?0.001).

Conclusion

Recurrent AKI is common among elderly patients who recovered their renal function post-AKI and is associated with significantly higher 12-month mortality compared with CKD patients.

     

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.     

Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of cyclosporine nephrotoxicity?

The aim of work was to investigate whether serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL, respectively) are potential biomarkers of early cyclosporine A (CsA) nephrotoxicity in steroid-dependent nephrotic children (SDNS). The study group (I) consisted of 19 children with SDNS aged 9.46?±?5.52 years treated with CsA. The children were examined four times: at proteinuria relapse, prior to CsA treatment, then after 3, 6, and 12 months of CsA treatment. The control group (II) consisted of 18 healthy children aged 3–15 years. A commercial enzyme-linked immunosorbent assay method was used to measure NGAL concentration. The sNGAL level in SDNS children prior to the administration of CsA was similar to that in the healthy controls (p?>?0.05), but it increased significantly during the course of treatment (p?<?0.01). The uNGAL/creatinine (cr) ratio in SDNS patients was higher before the withdrawal of CsA therapy (p?<?0.05), and was also increased at the consecutive examinations (p?<?0.01). There was a positive correlation between both sNGAL and uNGAL levels and CsA serum level. However, based on the serum and urinary NGAL/cr receiver operating characteristic curve and area under the curve (AUC) analysis, it remains uncertain whether uNGAL is a good predictor of cyclosporine nephropathy. Both sNGAL and uNGAL concentrations increased during the course of CsA treatment. Further studies in larger groups of patients are therefore necessary to confirm our experimental data that increased NGAL levels may be a non-invasive marker for the early detection of tubulointerstitial damage in CsA nephrotoxicity.     

Effects of the diagnostic window and duration of acute kidney injury on 1-year mortality in elderly patients: a single-center retrospective study

Background

We evaluated the prognostic impact of AKI duration on the 1-year mortality rate in elderly patients diagnosed based on the 48-hour and 7-day changes in serum creatinine (Scr) levels recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.

Methods

This retrospective study was conducted from 2007 to 2018 on elderly patients in the Geriatric Department of the Chinese PLA General Hospital. Based on the two diagnostic criteria in the KDIGO guidelines, the patients were divided into a 48-hour diagnostic window and a 7-day diagnostic window group, and into transient AKI (lasting 1–2 days) and persistent AKI (lasting 3–6 days, and?≥?7 days) based on the time at which the Scr level returned to the baseline value. The primary outcome was the 1-year mortality rate after AKI.

Results

In total, 688 patients were enrolled, including 367 (53.3%) with a 48-hour and 321 (46.7%) with a 7-day diagnostic window. Of the 688 patients, in the 48-hour window group, 12.0% had transient AKI, 31.1% had lasting 3–6 days, and 56.9% had lasting?≥?7 days; in the 7-day window group, 5.3% had transient AKI, 24.0% had lasting 3–6 days, and 70.7% had lasting?≥?7 days. Overall, 332 patients (33.6%) died within 1 year, including 189 (51.5%) in the 48-hour and 143 (44.5%) in the 7-day diagnostic window group. After adjusting for multiple covariates, AKI duration was associated with a significantly higher 1-year mortality rate (3–6 days: HR?=?3.535; 95% CI?=?1.685–7.417, P?=?0.001;?≥?7 days: HR?=?2.400; 95% CI?=?1.152–5.001, P?=?0.019) in the 48-hour diagnostic window group, but it did not differ in the 7-day diagnostic window group (P?=?0.452).

Conclusions

Persistent AKI was common in elderly hospitalized patients, accounting for 88% and 95% of patients with 48-hour and 7-day diagnostic windows, respectively. Moreover, AKI duration was associated with different clinical outcomes depending on the diagnostic window. Further studies should focus on the mechanism underlying the relationship of AKI outcomes with diagnostic criteria.