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.

     

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.     

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.     

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 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.     

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.     

Urinary kidney injury molecules in children with febrile seizures

Objective: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time.

Methods: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons.

Results: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p?>?0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9?±?9.8; 6.7?±?4.0, respectively; p?p?p?Conclusion: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.     

Utility of fractional excretion of urea in the differential diagnosis of acute kidney injury in children

Introduction

The fractional excretion of sodium (FE_Na) has been used as an index for the differential diagnosis of acute tubular necrosis (ATN) and prerenal acute kidney injury (AKI). The reliability of this index, however, decreases with the use of the diuretic agent furosemide. The fractional excretion of urea nitrogen (FE_UN) has been shown to be useful in such settings in adults. The objective of this study was to examine whether FE_UN is also useful in these settings in children.

Methods

We assessed 102 episodes of AKI in 74 children, classifying these into three groups based on history, physical examination, urine examination and subsequent clinical course: (1) prerenal AKI without furosemide (N?=?37), (2) prerenal AKI with furosemide (N?=?32) and (3) ATN (N?=?33).

Results

Of the 37 prerenal AKI episodes without furosemide, 35 showed low FE_Na of <1 %, with an overall average of 0.35?±?0.11 %, whereas prerenal AKI with furosemide (1.63?±?0.37 %) and ATN (8.76?±?2.11 %) were associated with a higher FE_Na. FE_UN in the clinical setting of prerenal AKI was lower than that in ATN (27.9?±?2.1 vs. 51.6?±?3.8 %, respectively) and, in contrast to FE_Na, not significantly different between the categories of prerenal AKI with and without furosemide (29.2?±?3.1 vs. 25.1?±?2.9, respectively). The sensitivity of FE_UN <35 % was 75 % in prerenal AKI with furosemide, whereas that of FE_Na was 53 %.

Conclusions

FE_UN is useful in detecting prerenal AKI in children administered furosemide.

     

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.     

Amelioration of cisplatin-induced acute kidney injury by recombinant neutrophil gelatinase-associated lipocalin

We investigated the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) in a murine model of cisplatin-induced nephrotoxicity. Male Swiss-Webster mice were assigned to four groups (n?=?10 in each group). Control mice received vehicle only. Mice in the experimental group were given a single intraperitoneal injection of cisplatin (20?mg/kg) to induce nephrotoxicity, and were divided into three groups. The first group received 100?μL of saline only via tail vein at the time of cisplatin administration. The second group was given biologically active recombinant NGAL via tail vein (250?μg/100?μL solution). The third group was injected with a 250?μg/100μL solution of inactivated NGAL. After 4 days, we measured serum creatinine and urinary N-acetyl-β-d-glucosaminidase (NAG), and performed histologic studies. Biologically active NGAL significantly blunted the rise in serum creatinine (NGAL plus cisplatin 1.33?±?0.31 versus cisplatin alone 2.43?±?0.31?mg/dL, p?<?.001) as well as the increase in urine NAG (NGAL plus cisplatin 60.7?±?14.2 versus cisplatin alone 120.5?±?22.5 units/gm creatinine, p?<?.005). In addition, NGAL conferred a marked reduction in tubule cell necrosis and apoptosis (NGAL plus cisplatin 6.9?±?1.2 versus cisplatin alone 15.1?±?3.4 TUNEL positive nuclei per 100 cells, p?<?.001). These beneficial effects were completely abolished when heat-inactivated NGAL was administered instead of the biologically active form. Since induction of NGAL in kidney tubules is a known physiologic response to cisplatin, the pharmacologic use of NGAL to prevent cisplatin nephrotoxicity is likely to be safe and effective.     

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.     

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.     

NGAL and NT-proBNP levels in diabetic patients with macroproteinuria

Abstract

Background: In patients with heart failure plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are correlated to urine neutrophil gelatinase-associated lipocalin (NGAL) levels. We prospectively evaluated the relationship among glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), urine and serum NGAL and NT-proBNP levels in 20 type II diabetic patients with macroalbuminuria at 4-month intervals. Results: Compared with 20 age, gender-matched healthy controls, diabetic patients had higher urine and serum NGAL, serum NT-proBNP and lower eGFR. The eGFR of the patients at the baseline, the 4th and the 8th month were 29.6?±?12.0, 27.8?±?13.7 and 22.9?±?10.4?mL/min/1.73?m², respectively. No significant change in urine NGAL levels was detected (p?>?0.05), whereas there were significant increases in NT-proBNP, serum NGAL and urine ACR and significant decrease in eGFR as the study progressed (p?<?0.05). Both the baseline and the 4th month urine ACR were positively correlated to NT-proBNP levels measured at the same periods (r: 0.451; p: 0.046; r: 0.489; p: 0.029 respectively). In all measurements, urine ACR was negatively correlated to serum albumin levels measured at the same periods (r: ?0.792; p: 0.000; r: ?0.716; p: 0.000; r: ?0.531; p: 0.016 respectively). None of eGFR measurements was correlated with NT-proBNP (p?>?0.05). Neither serum NGAL nor urinary NGAL levels are associated with NT-proBNP (p?>?0.05). Conclusion: Our findings show an association between NT-proBNP and proteinuria in type II diabetic patients with macroalbuminuria but not with serum and urine NGAL.     

Low levels of high-density lipoproteins are associated with acute kidney injury following revascularization for chronic limb ischemia

Abstract

Objectives: Perioperative acute kidney injury (AKI) is not uncommon, following revascularization. HDL has been shown to reduce organ injury in animal models. The aim of the study is to examine the association of HDL on AKI in patients undergoing revascularization for chronic limb ischemia. Methods: All patients who underwent revascularization between June 2001 and December 2009 were analyzed. Patients on dialysis and with incomplete data were excluded. Patients were grouped for HDL < or ≥40?mg/dL. Univariate and multivariate analysis were used to identify factors associated with AKI. Results: A total of 684 patients were included. Eighty-two (12.0%) patients developed postoperative AKI (15.7% in low HDL group vs. 6.3% in high HDL group, p?<?0.001). The AKI group were more likely to be older (71.5?±?10.1 vs. 68.0?±?10.8, p?=?0.01), ASA 4 class (26% vs. 14%, p?<?0.001), to have albumin <3?g/dL (59% vs. 32%, p?<?0.001), low HDL levels (79% vs. 58%, p?<?0.001), DM (61% vs. 44%, p?=?0.005), CAD (67% vs. 55%, p?=?0.003), preoperative chronic kidney disease (CKD) stage III–IV (55% vs.39%, p?<?0.001), to present with critical limb ischemia (82% vs. 63%, p?=?0.001), and to be on ACEI (67% vs. 51%, p?=?0.006). Multivariate logistic regression analysis showed low HDL (Odds Ratio (OR) 1.66 [1.23–2.24]) and serum albumin levels <3?g/dL (OR 1.66 [1.29–2.13], p?<?0.001) were independently associated with increased odds for developing AKI. Propensity score analyses showed low HDL was independently associated with increased odds of AKI (OR 2.4 (1.4–4.2)). Conclusions: AKI following revascularization is not uncommon (12.0%), and lower concentrations of HDL and serum albumin are associated with increased odds of postoperative AKI. There was also a trend of higher prevalence of AKI among those with pre-existing CKD.     

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.

     

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.     

The expression of response gene to complement 32 on renal ischemia reperfusion injury in rat

To investigate the expression of response gene to complement 32 (RGC32) in rat with acute kidney injury (AKI) and to explore the role of RGC32 in renal injury and repair induced by ischemia reperfusion. Rats were randomly divided into two groups, including sham operation group (n?=?48) and acute ischemia reperfusion injury (IRI) group (n?=?48). Rats were sacrificed following reperfusion 2?h, 6?h, 24?h, 48?h, 72?h, 1 week (w), 2 w, and 4 w. The distribution and expression of RGC32 in renal tissue were observed by means of immunohistochemistry. The mean density of the images detected by Image-Pro Plus 6 was designated as the representative RGC32 expression levels. Meanwhile, RGC32 mRNA expression was measured by qPCR. RGC32 mainly expressed in cytoplasm of proximal tubular epithelial cells. However, RGC32 did not express in renal interstitium and vessels. The expression levels of RGC32 measured by immunohistochemistry at different reperfusion time were 0.0168?±?0.0029, 0.0156?±?0.0021, 0.0065?±?0.0013, 0.0075?±?0.0013, 0.0096?±?0.0014, 0.0132?±?0.0016, 0.0169?±?0.0014, 0.0179?±?0.0022, respectively. Compared with the sham group, the level of RGC32 expression in IRI group was significant lower at 24?h, 48?h, 72?h after IRI (p?in vitro experiments show the expression of α-SMA and extracellular matrix expression increased signification when the RGC32 was silenced. Our data showed that the RGC32 expression in AKI rat decreased significantly reduces with different reperfusion time and performs a time-dependent manner. RGC32 may play an important role in the pathogenesis of AKI following IRI and repair in rat.     

Acute kidney injury in the elderly hospitalized patients

Objective: We aimed to evaluate acute kidney injury (AKI), occurrence of recovery and risk factors associated with permanent kidney injury and mortality in the elderly individuals. Design: Evidence for this study was obtained from retrospective cohort study from our center. Patients: A total of 193 patients (>65 years, mean age: 79.99?±?6.93) with acute kidney injury were enrolled in this study between 2011 and 2012. Patients with kidney failure or renal replacement therapy (RRT) history at admission were excluded. Intervention: Main outcome measurements: serum creatinine (SCr), estimated GFR (with CKD-Epi) and complete blood counts were evaluated at baseline and daily basis thereafter. The AKI was defined based on Kidney Disease Improving Global Outcomes (KDIGO) classification. Results: Among 193 patients, 43 (22%) patients required RRT. Mortality rate was 18% (n?=?36) SCr levels were restored within 9.9?±?6.7days on average (8–39 days). Sixteen patients (12.7%) required RRT after discharge. The mean hospital stay was 10.1?±?8.6 days (7–41 days). Mortality rate of patients who have no renal recovery was higher (44.8% vs. 4.8%) than renal recovery group (p?0.01). Conclusion: The AKI represents a frequent complication in the elderly patients with longer hospital stay and increased mortality and morbidity. Our results show that dialytic support requirement is an independent predictor of permeant kidney injury in the elderly AKI patients. Older age, low diastolic blood pressure, high CRP and low hemoglobin levels were independent risk factors for mortality.     

L-Carnitine inhibits eryptosis induced by uremic serum and the related mechanisms

Abstract

Objective: To investigate whether L-carnitine (LC) inhibits eryptosis induced by uremic serum and the related mechanism. Methods: One percent erythrocyte suspension was cultured by three kinds of mediums in vitro, which was included in the control group (Group C, phosphate buffered saline [PBS]), the uremic serum group (Group U, 30% uremic serum?+?70% PBS) and the LC group (Group L, 30% uremic serum?+?70% PBS?+?200?umol/L LC), respectively. Erythrocytes were collected at 24 and 48?h, respectively. Phosphatidylserine (PS) was estimated from Annexin-V-binding and reactive oxygen species (ROS) by flow cytometry, glutathione (GSH) was estimated from Enzyme linked immunosorbent assays (ELISA) by Microplate reader. Results: Eryptosis in Group C increased as the incubating time extended (3.43?±?0.37 at 24?h, 4.21?±?0.44 at 48?h). Eryptosis increased in Group U compared with Group C (6.5 1?±?0.71 at 24?h, p?<?0.01; 8.55?±?0.76 at 48?h, p?<?0.01), while decreased in Group L compared with Group U (5.80?±?0.69 at 24?h, p?<?0.05; 7.87?±?0.76 at 48?h, p?<?0.05). Meanwhile, ROS of erythrocytes increased in Group U compared with Group C (33.12?±?1.61 versus 14.83?±?2.22 at 24?h, p?<?0.01; 42.06?±?1.81 versus 20.94?±?1.78 at 48?h, p?<?0.01), and GSH decreased in Group U compared with Group C (25.66?±?0.32 versus 31.27?±?0.38 at 24?h, p?<?0.01; 8.53?±?0.59 versus 17.29?±?0.54 at 48?h, p?<?0.01). ROS of erythrocytes decreased in Group L compared with Group C (26.29?±?1.69 at 24?h, p?<?0.01; 36.21?±?2.00 at 48?h, p?<?0.01). GSH increased in Group L compared with Group U (27.54?±?0.60 at 24?h, p?<?0.01; 15.18?±?0.42 at 48?h, p?<?0.01). Conclusions: LC inhibits eryptosis induced by uremic serum, which possibly relates to oxidative stress in part.     

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.