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.     

Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60?ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6?h of injury, and between 12 and 36?h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60?ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6?h of injury, and between 6 and 12?h, all AUCs except AP were between 0.68 and 0.78. Beyond 12?h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.     

Longitudinal patterns of urine biomarkers in infants across gestational ages

Background

Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age.

Methods

Fifty-two infants ranging from 24 to 41 weeks’ GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD).

Results

Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m² with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p?=?0.002. When factored by urine creatinine CysC/cr?+?ALB/cr were the most significant functional markers with AUC?=?0.79; p?=?0.004; sensitivity 96 %; specificity 58 %.

Conclusions

Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury.

     

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.     

Evaluation of serum cysteine-rich protein 61 and cystatin C levels for assessment of acute kidney injury after cardiac surgery

Objective The occurrence of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) can lead to morbidity and mortality. We hypothesized that cysteine-rich protein 61 (CYR61) and cystatin C (CysC) may be potential novel biomarkers of AKI after cardiopulmonary bypass. Methods Patients were classified into AKI and non-AKI group depending on serum creatinine. Levels of creatinine, CysC, and CYR61 were measured at five time-points before and within 48?h after the surgery. Results Fifty patients were included in the study. Serum creatinine pre-operative values were 74.0?±?43.3?μmol/L in AKI group vs. 64.8?±?17.9?μmol/L in non-AKI group. During 48?h, the values increased to 124.6?±?67.2?μmol/L in AKI group (p?<?0.001) but in non-AKI group they did not change significantly. Serum CysC values were significantly increased already 2?h after CBP in AKI group (949?±?557?μg/L, p?<?0.05) compared to non-AKI group (700?±?170?μg/L). Pre-operative serum CYR61 tended to be lower in AKI group (12.4?μg/L) than in non-AKI group (20.3?μg/L), but 24?h after the surgery, the levels in AKI group tended to be higher than non-AKI group. Conclusion Serum CYR61 does not seem to be an early predictor of AKI in patients after cardiac surgery with CPB, but it might possibly identify patients at risk of developing more severe kidney injury. Serum CysC could be a promising biomarker of AKI, differentiating patients at risk of developing AKI after cardiac surgery as early as 2?h after surgery.     

Urinary netrin-1 and KIM-1 as early biomarkers for septic acute kidney injury

Background: Acute kidney injury (AKI) during sepsis is associated with poor outcome. However, diagnosis of AKI with serum creatinine (SCr) level change is neither highly sensitive nor specific. Therefore, identification of novel biomarkers for early diagnosis of AKI is desirable. Aims: To evaluate the capacity of combining urinary netrin-1 and human kidney injury molecule type 1 (KIM-1) in the early diagnosis of septic AKI. Methods: We prospectively recruited 150 septic patients from Jun 2011 to Jun 2013 at Zhejiang Provincial People's Hospital, China. SCr, urinary netrin-1, and KIM-1 levels were recorded at 0, 1, 3, 6, 24, and 48?h of ICU admission and compared between AKI and non-AKI patients. In addition, we investigated the prognostic value of netrin-1 and KIM-1 between non-survivors and survivors in septic AKI patients. Results: SCr levels started to show elevation after 24?h of ICU admission. However, netrin-1 levels increased significantly as early as 1?h, peaked at 3–6?h and remained elevated up to 48?h of ICU admission in septic AKI patients. KIM-1 increased significantly by 6?h, peaked at 24?h and remained significantly elevated until 48?h of ICU admission. Furthermore, we observed significant higher urinary KIM-1 levels at 24?h and 48?h in non-survivors compared to survivors in AKI patients. Conclusions: Our results suggest that both netrin-1 and KIM-1 are clinically useful as early biomarkers in the diagnosis of septic AKI. In addition, persistent elevation of urinary KIM-1 level may be associated with poor prognosis.     

Potential biomarkers for the early detection of acute kidney injury after percutaneous nephrolithotripsy

This study aims to investigate the role of urinary biomarkers in the determination of the potential risks of renal parenchymal tubular damage in adult patients who underwent percutaneous nephrolithotomy (PNL) with the indication of renal stone. A randomized and prospective controlled study was performed between June and December 2013. We enrolled 29 consecutive patients with renal calculi?>?2?cm and who underwent PNL, as well as 47 healthy control subjects. Urine samples, including 2 h before surgery, 2 and 24 h after surgery were collected from the patient group. Freshly voided urine samples were collected from the control group. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-glucosaminidase (NAG), and liver-type fatty acid binding protein (LFABP) levels were measured from these urine samples. The mean KIM-1/Cr value that measured 24 h after the operation was statistically significant, higher than its preoperative (preop) level (p?= 0.045). A significant difference was detected between the mean preop and postoperative (postop) 24 h NAG/Cr values (p?< 0.001). Also, postop 24 h NGAL/Cr levels were statistically significant, higher than its preop levels (p?= 0.013). According to the comparison of preop and postop levels, an increase in LFABP/Cr values secondary to surgical intervention was observed without any statistically significant difference. Besides the LFABP/Cr levels do not change after percutaneous kidney surgery, KIM-1/Cr, NAG/Cr, and NGAL/Cr levels increase postop period, especially at 24 h. Further studies with a larger series and repeated measurements should be performed to clarify if they can be used to demonstrate renal damage after percutaneous surgery or not.     

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.     

Serum NGAL,cystatin C and urinary NAG measurements for early diagnosis of contrast-induced nephropathy in children

Aim: The study investigated a number of biomarkers for the early diagnosis of contrast-induced nephropathy (CIN), which is an important cause of acute kidney injury (AKI). Material and methods: The study included 91 children scheduled for elective cardiac angiography and 50 healthy controls. Biomarkers including serum (s) and urinary (u) sodium, serum and u-creatinine, s-cystatin-C, serum neutrophil gelatinase-associated lipocalin (NGAL) and urinary N-acetyl beta glucosaminidase (u-NAG)/creatinine ratio were measured 4 times sequentially in the patients and once in the controls. Results: The patient group comprised 40 males (44%) and 51 females (56%) while the control group comprised 16 males (32%) and 34 females (68%). Age, gender, s-creatinine, estimated-glomerular filtration rate (eGFR), s-cystatin-C and fractional-excretion of sodium did not differ significantly between the groups. Serum sodium and s-NGAL were found to be lower in the patients than those of in the controls, while their u-NAG/creatinine ratio was found to be higher. Sequential data analysis revealed that s-NGAL and u-NAG/creatinine ratio increased in the first 6?h after radiocontrast media (RCM) administration and decreased at 12 and 24?h. Serum BUN and s-cystatin-C levels also showed a significant difference during the 24-h follow-up. eGFR, s-sodium and s-creatinine levels did not change in the following period. Serum cystatin-C levels revealed a significant negative correlation with eGFR. Administered RCM doses showed a positive correlation only with u-NAG/creatinine ratios. Conclusion: In the first 24?h, s-cystatin-C, s-NGAL and especially u-NAG/creatinine ratio showed promise as biomarkers, but eGFR is not adequate for early diagnosis of CIN. Sequential measurement of biomarkers may contribute to more accurate diagnosis of AKI.     

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.     

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.     

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.

     

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.     

A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study

Background

The goal of this study was to assess the value of a urinary biomarker profile comprised of neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates.

Methods

We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n?=?25) or extracorporeal membrane oxygenation (ECMO) (n?=?10). Urine was collected at baseline, 48 h of illness, and?>?24 h post-recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 h and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50 % post-recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data.

Results

Fifteen at-risk newborns had AKI. In the first 48 h of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74 % and specificity of 84 %. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery identified critically ill neonates with AKI.

Conclusions

These findings require validation in larger prospective studies.     

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.     

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.     

尿肝型脂肪酸结合蛋白及其与尿中性粒细胞明胶酶相关脂质运载蛋白联合应用在成人心脏手术后急性肾损伤诊断中的作用

目的 探讨尿肝型脂肪酸结合蛋白( L-FABP)及其与尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)联合应用在预测成人心脏手术后急性肾损伤(AKI)的发生及严重程度中的价值,以期能为临床AKI的早期诊断提供方便可靠的方法.方法 前瞻性收集心脏手术患者术前、术后即刻及术后2h的血和尿标本,分别检测Scr、尿L-FABP和NGAL水平,比较AKI和非AKI患者术后各标志物的动态变化情况.运用受试者工作特征(ROC)曲线及曲线下面积(AUC)评估标志物单独及联合应用时诊断AKI的准确性.结果 总共109例患者中26例(23.9％)发生了AKI,其中AKIN Ⅰ、Ⅱ和Ⅲ期分别占46.2％ 、34.6％和19.2％.尿L-FABP 和NGAL水平在AKI组术后即刻及术后2h均显著高于非AKI组,其浓度变化明显早于Scr.两时间点各标志物单独预测AKI的发生及Ⅱ和Ⅲ期AKI的AUC均在0.81～0.87.用Logistic 回归方程联合术后同一时间点的尿NGAL和尿L-FABP,则术后即刻和术后2h预测术后AKI 及严重程度的精确性进一步提高( AUC=0.911～0.927).结论 尿L-FABP和尿NGAL在心脏术后AKI早期即显著升高,比Scr能更早地预测AKI的发生和严重程度,两者联合应用则可使诊断的精确性进一步提高.     

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.     

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.     

Early detection of acute kidney injury by serum cystatin C in critically ill children

Background

We prospectively evaluated whether serum cystatin C (CysC) detected acute kidney injury (AKI) earlier than basal serum creatinine (Cr).

Methods

In 107 pediatric patients at high risk of developing AKI, serum Cr and serum CysC were measured upon admission. Baseline estimated creatinine clearance (eCCl) was calculated using a CysC-based glomerular filtration rate (GFR) equation from a serum Cr measured at the pediatric intensive care unit (PICU) entrance.

Results

The median age was 10 months (interquartile range, 3–36 months). Serum Cr, serum CysC, and eCCl (mean ± standard deviation [range]) were 0.5?±?0.18 mg/dl (0.2–1.1 mg/dl), 0.53?±?0.78 (0.01–3.7 mg/l), and 72.55 ± 28.72 (20.6–176.2) ml/min per 1.73 m², respectively. The serum CysC level in patients with AKI was significantly higher than children with normal renal function (p?<?0.001). The values for the cut-off point, sensitivity, specificity, and the area under curve (AUC) were determined for CysC as 0.6 mg/l, 73.9 %, 78.9 %, and 0.92 [95 % confidence interval (0.82–1)], respectively, and for Cr the values were 0.4 mg/dl, 68 %, 46.2 %, and 0.39, [95 % confidence interval (0.24–0.54)], respectively. The receiver operating characteristics (ROC) curve analysis revealed that CysC had a significantly higher diagnostic accuracy than eCCl (p?<?0.001).

Conclusions

Our results identify that the sensitivity of serum CysC for detecting AKI is higher than that of serum Cr in a heterogeneous pediatric intensive care unit (PICU) population.