Early Biomarker Of Acute Kidney Injury Research Articles

A-309 Multicenter Performance Evaluation of the ProNephro AKITM Assay and Sample Stability in Pediatric Patients

Abstract Background Acute Kidney Injury (AKI), defined by increased serum creatinine or decreased urine volume, is highly prevalent in critically ill pediatric patients. Those who develop AKI experience worsened outcomes, raising the need for accurate and early biomarkers for AKI. Relying in serum creatinine for AKI diagnosis is unreliable due to its diagnostic inaccuracy and delayed rise in the AKI pathophysiology. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a novel and widely studied biomarker for early identification of AKI. During pathological progression, NGAL is elevated in blood and urine within two hours of the insult, making it useful for early diagnosis and management of kidney injury in critically ill children. This study aims at evaluating the performance characteristics of a quantitative test for NGAL in urine intended for use in critically ill pediatric patients, and investigating the stability of NGAL in pediatric urine. Methods The ProNephroAKITM is a particle-enhanced turbidimetric immunoassay on the Roche cobas® c501 analyzer to measure NGAL quantitatively in urine in pediatric patients 3 months to 21 years of age. These studies were approved by the respective institutional review boards. The limits of blank (LOB), detection (LOQ) and quantitation (LOQ) were determined following CLSI EP17A2. Linearity was assessed across the measurement range (MR) of 50-3000 ng/mL. The assay repeatability, between-run, between-day and total imprecision were determined in pediatric urine samples (n=9, covering the MR) and controls (n=2) following CLSI EP5-03 guidelines. Likewise, multisite reproducibility was evaluated in pediatric urine (n=7, covering the MR) and controls (n=2) in 3 laboratories and alternating operators. The assay specificity was assessed in the presence of several endogenous and exogeneous substances (e.g. drugs, contrast agents), potential related cross-reactant molecules, and several pH-values. The stability of NGAL in urine was evaluated using freshly collected pediatric urine samples covering the MR from 16 consented patients after storage at ambient (15-30°C), refrigerated (2-8°C), and frozen temperatures (≤-70°C), and following 3 freeze/thaw cycles. Results The ProNephroAKITM is linear across the MR of 50-3000 ng/mL. The LOB, LOD and LOQ were 9, 14 and 18 ng/mL, respectively. The coefficients of variation (CVs) for repeatability, between-run, between-day and total precision were ≤5.0%, ≤3.1%, ≤1.7% and ≤4.9%, respectively in urine and control samples. The reproducibility across 3 independent laboratories was ≤6.6%. The recovery of NGAL was not significantly affected by endogenous substances, contrast agents, pH (3.3-10.3), and common and special pharmaceutical compounds (exception: very high Cefepime concentrations may decrease NGAL), and potential cross-reactants. Freshly collected urine samples spanning concentrations from 71-2,373 ng/mL were stable (±10% recovery) for 2 days at ambient, 4 days refrigerated and 13 months frozen, and after 3 freeze/thaw cycles. Conclusions We report the performance characteristics of the ProNephroAKITM assay, including excellent precision and adequate reproducibility across 3 laboratories, sensitivity, specificity, and urine sample stability. The test was determined to meet the analytical performance required for clinical use in critically ill pediatric patients at risk of developing or having persistent AKI.

Potential use of Oncostatin M in Critically ill Patients with acute Kidney Injury

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications affecting patients admitted to intensive care unit (ICU) worldwide. In response to injury, both kidneys and liver secrete acute phase reactants as a mechanism of protection. Oncostatin M (OSM) is a member of the interleukin-6 family of cytokines which was found to be elevated during renal injury as in diabetic nephropathy, glomerulonephritis, and obstructive nephropathy. AIM: The study aimed to assess the role of OSM as an early biomarker of AKI in critically ill patients. PATIENTS AND METHODS: We conducted a prospective case–control study that included 202 patients admitted to ICU within Kasr El-Aini University hospitals during the period between January 2022 and August 2022. Eligible patients were divided into two groups according to the occurrence of AKI, and Oncostatin was assessed in the sera of the included patients. RESULTS: Our findings showed that the AKI group had statistically significant lower OSM levels compared to the control group, especially among those patients who had poor clinical outcomes and non-survivors. We also found that OSM is a good predictive tool for the prediction of mortality among patients admitted to ICU with sepsis complicated with AKI (Area under the curve = 0.673, 95% confidence interval: 0.532–0.814) with a sensitivity of 83.8% and specificity of 61.4%. CONCLUSION: OSM plays an important role among critically ill patients who are admitted to the ICU with sepsis, it can significantly predict AKI development and subsequent mortality.

Assessment of urine CCL2 as a potential diagnostic biomarker for acute kidney injury and septic acute kidney injury in intensive care unit patients

Acute kidney injury (AKI) is a prevalent and serious condition in the intensive care unit (ICU), associated with significant morbidity and mortality. Septic acute kidney injury (SAKI) contributes substantially to AKI cases in the ICU. However, current diagnostic methods have limitations, necessitating the exploration of novel biomarkers. In this study, we investigated the potential of plasma and urine CCL2 levels as diagnostic markers for AKI and SAKI in 216 ICU patients. Our findings revealed significant differences in plasma (p < 0.01) and urine CCL2 (p < 0.0001) levels between AKI and non-AKI patients in the ICU. Notably, urine CCL2 demonstrated promising predictive value for AKI, exhibiting high specificity and sensitivity (AUC = 0.8976; p < 0.0001). Furthermore, we observed higher urine CCL2 levels in SAKI compared to non-septic AKI (p < 0.001) and urine CCL2 could also differentiate SAKI from non-septic AKI (AUC = 0.7597; p < 0.0001). These results suggest that urine CCL2 levels hold promise as early biomarkers for AKI and SAKI, offering valuable insights for timely intervention and improved management of ICU patients.

Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: An animal experimental study.

Early assessment of the severity of acute kidney injury (AKI) is critical to the prognosis of patients. Renal microcirculation hemodynamic changes and inflammatory response are the essential links of AKI induced by ischemia-reperfusion injury (IRI). This study aims to explore the value of contrast-enhanced ultrasound (CEUS) based on vascular cell adhesion molecule-1 (VCAM-1) targeted microbubbles (TM) in evaluating the renal microcirculation hemodynamics and inflammatory response of different severity of AKI. Eighteen male C57BL/6J mice were randomly divided into three groups (n = 6): sham operation (sham) group, mild IRI-AKI (m-AKI) group, and severe IRI-AKI (s-AKI) group. CEUS based on VCAM-1 TM was used to evaluate renal microcirculation perfusion and inflammatory response. Pearson's correlation was used to analyze the correlation between ultrasonic variables and pro-inflammatory factors. Compared with the sham group, AUC in m-AKI and s-AKI groups was significantly decreased, and s-AKI group was lower than m-AKI group (P < 0.05). NID of m-AKI and s-AKI groups was significantly higher than that of the sham group, and s-AKI group was higher than that of m-AKI group (P < 0.05). There was a linear positive correlation between NID and VCAM-1 protein expression (r = 0.7384, P < 0.05). NID and AUC were correlated with TNF-α and IL-6 levels (P < 0.05). Compared with early AKI biomarkers, CEUS based on VCAM-1 TM has higher sensitivity in evaluating the severity of AKI. CEUS based on VCAM-1 TM can evaluate renal microcirculation perfusion and inflammatory response in mild and severe AKI, which may provide helpful information for assessing the severity of AKI.

Rhabdomyolysis aggravates renal iron accumulation and acute kidney injury in a humanized mouse model of sickle cell disease

Individuals with sickle cell disease (SCD) are at greater risk of rhabdomyolysis, a potentially life-threatening condition resulting from the breakdown of skeletal muscle fibers. Acute kidney injury (AKI) is one of the most severe complications of rhabdomyolysis. Chronic kidney and cardiovascular disease, which account for SCD mortality, are long-term consequences of AKI. Although SCD elevates the risks of rhabdomyolysis-induced sudden death, the mechanisms that underlie rhabdomyolysis-induced AKI in SCD are unclear. In the present study, we show that, unlike their control non-sickling (AA) counterparts, transgenic homozygous SCD (SS; Townes model) mice exhibited 100% mortality 8–24 h after intramuscular glycerol injection. Five hours after glycerol injection, SS mice showed a more significant increase in myoglobinuria and plasma creatine kinase levels than AA mice. Basal plasma heme and kidney tissue iron levels were significantly higher in SS than in AA mice. In contrast to AA, glycerol-induced rhabdomyolysis aggravated these parameters in SS mice. Rhabdomyolysis also amplified oxidative stress in SS compared to AA mice. Glycerol-treated SS mice exhibited worse renal function, exemplified by a reduction in GFR with a corresponding increase in plasma and urinary biomarkers of early AKI and renal tubular damage. The free radical scavenger and Fenton chemistry inhibitor, TEMPOL, ameliorated rhabdomyolysis-induced AKI in the SS mice. These findings demonstrate that oxidative stress driven by renal iron accumulation amplifies rhabdomyolysis-induced AKI in SCD mice.

Predictive ability of 2-h serum neutrophil gelatinase-associated lipocalin for perinatal asphyxia-induced acute kidney injury.

Acute kidney injury (AKI) is a common cause of mortality and morbidity in asphyxiated newborns. Recent research suggests serum neutrophil gelatinase-associated lipocalin (sNGAL) as an early biomarker of AKI in newborns with perinatal asphyxia. The prospect of sNGAL is yet to be studied in Nigeria, with a huge burden of asphyxia-related neonatal deaths. A cross-sectional analytic study was conducted on 53 asphyxiated term newborns and 53 healthy babies at the newborn unit of the Wesley Guild Hospital Ilesa, Nigeria. sNGAL was assessed in all neonates with perinatal asphyxia at baseline (within 30min of delivery), 2h, and 48h of life. Mean sNGAL was significantly higher in asphyxiated newborns than in the control group, 81.4 (45.9) vs. 53.7 (29.2), p < 0.001. However, the mean 2-h sNGAL levels were similar in asphyxiated babies with and without AKI 100.5 (36.7) ng/ml vs. 85.3 (31.4) ng/ml, p = 0.115. The 2-h sNGAL with an AUC of 0.61 at an 83.0ng/ml cut-off had an acceptable discriminating capability of predicting AKI. The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 51.5%, 50%, and 81%, respectively. This study shows that sNGAL levels were significantly elevated in newborns with perinatal asphyxia compared to healthy neonates, but the 2-h sNGAL is less predictive of AKI in newborns with perinatal asphyxia. The negative predictive value is high, and this may find some relevance in the attempts at early exclusion of asphyxiated babies prone to AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Establishment and assessment of a preclinical model of acute kidney injury induced by contrast media combined acute myocardial ischemia reperfusion surgery.

Acute kidney injury (AKI) is a common complication after acute myocardial infarction (AMI) in clinical practice, and the majority of previous preclinical models were induced by a single factor. The objective of the present study was to establish a stable preclinic model of AKI induced by contrast media (CM) with acute myocardial ischemia reperfusion surgery and to identify the effect of oxidative stress on kidney injury. Rats were treated individually or with CM or myocardial ischemia reperfusion surgery. Renal baseline and AKI parameters, the level of oxidative stress and histopathological images were examined along with AKI biomarkers. Results showed the incidence of AKI in the CM group and ischemia reperfusion injury (IRI) group was 40%, χ2 test (P<0.05 vs. CM-IRI) and 35%, χ2 test (P<0.05 vs. CM-IRI) and the combination group had the highest incidence rate 75%. IRI surgery combined with CM diminished kidney function and induced oxidative stress by increasing creatinine, blood urea nitrogen and reactive oxygen species levels. Western blotting showed that the early AKI biomarker of NGAL and KIM-1 increased and that the combination group had the highest value. Pathology damage exhibited severe kidney damage in the combination group compared with other control groups. The present research established a reliable preclinic model of post-AMI AKI with a stable and high postoperative AKI rate. Additionally, CM was demonstrated to exacerbate AKI caused by acute myocardial infarction through oxidative stress and, thus, oxidative stress may be a potential therapeutic target.

Assessment of the diagnostic ability of RIFLE classification and neutrophil gelatinase-associated lipocalin biomarker in detecting acute kidney injury in newborns at the intensive care unit

Introduction/Objective. This study was designed to demonstrate the association of the RIFLE classification and neutrophil gelatinase-associated lipocalin (NGAL) in predicting of newborns with acute kidney injury (AKI). Methods. This was a prospective study. We included 100 newborns suspected of having a kidney injury. These newborns were admitted to the intensive care unit (ICU) at the University Clinic of Pediatrics from the period of two years. The severity of the disease was determined by RIFLE classification. The biochemical marker NGAL was included in this study because it is an early biomarker of AKI in newborns. The statistical processing of the material was by methods of descriptive statistics. Results. The prevalence rate of AKI was 6.25%, but according to the RIFLE classification the prevalence was 8.7%. According to RIFLE classification, we reported ?risk? in 36%, ?injury? in 50% and ?failure? in 14% of newborns with AKI. In newborns with perinatal asphyxia, kidney injury was seen in 34% and 30%, making perinatal asphyxia the most common predisposing factor. The difference in average value of the score for neonatal acute physiology with perinatal extension in newborns with AKI and the control group without AKI was confirmed significant (p &lt; 0.001). Also, there was a significant difference (p &lt; 0.001) between serum creatinine and urinary NGAL values, on the day they were admitted to the ICU. Conclusion. In newborns hospitalized in the ICU, AKI is a serious condition. We could identify kidney injury and follow up the progression of the disease by using RIFLE classification. The need for early diagnosis of kidney injury, in a period when the disease is not clinically manifest, in the first hours of its occurrence, is provided by NGAL.

Abstract 12488: Serum Cystatin C is an Early Predictor of Acute Renal Injury in Infants After Cardiac Surgery With Cardiopulmonary Bypass

Introduction: Acute kidney injury (AKI) following infant cardiac surgery is common, with increased morbidity and mortality. Changes in urine output and/or serum creatinine (SCr) are unreliable in the detection of AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, and lag behind onset of renal injury. Serum Cystatin C (SCC) has been used as a biomarker of AKI in adults and older children. If SCC predicts AKI in infants following cardiopulmonary bypass (CPB) is unknown. Hypothesis: SCC is an early biomarker of AKI following infant cardiac surgery requiring CPB. Methods: 42 infants (&lt; 1 year of age) were prospectively enrolled when presenting for cardiac surgery requiring CPB. SCC and SCr were measured at baseline (pre-operatively), and at 12, 24, and 48 hours following CPB initiation, and changes in SCC and SCr compared to baseline (ΔSCC and ΔSCr, respectively) were calculated. AKI was defined using KDIGO guidelines, as an increase in SCr ≥ 50% and/or a urine output &lt; 0.5mL/kg/hr for ≥ 6-12 consecutive hours in the first 3 post-operative days. Subjects were divided in 2 groups: AKI and non-AKI. Receiver Operating Characteristic (ROC) curves were utilized to predict AKI based on ΔSCC and ΔSCr, and the area under the curve (AUC) was quantified. Results: AKI occurred in 17 (40.4%) subjects. Baseline SCC and SCr measurements were similar between groups, as were age, gender, weight, and CPB time. Post-operative SCC values decreased from baseline, suggesting volume overload. While SCC concentrations did not differ significantly between the 2 groups, ΔSCC measurements were significantly different in those with AKI at 12 hours (0.2 ± 0.3 vs 0.4 ± 0.2; p &lt; 0.01) and remained different at 24 hours (0.1 ± 0.3 vs 0.3 ± 0.2; p = 0.02). ΔSCr measurements were significantly greater in the AKI group at 24 hours (0.1 ± 0.1 vs 0.0 ± 0.1; p &lt; 0.01) and 48 hours (0.1 ± 0.1 vs. 0.0 ± 0.1; p &lt; 0.01) but not at 12 hours. ROC curves demonstrated that both the ΔSCC at 12 hours (AUC = 0.72; p = 0.02) and the ΔSCr at 24 hours (AUC= 0.78; p &lt; 0.01) predicted AKI. Conclusions: The 12 hour ΔSCC predicts AKI in infants after cardiac surgery, and correlated with a rise in ΔSCr the following day. Earlier detection of AKI would allow earlier post-operative intervention to mitigate renal injury in infants.

Renal-Resistive Index for Prediction of Acute Kidney Injury in the Setting of Aortic Insufficiency

Acute kidney injury (AKI) is a common postoperative complication after cardiac surgery with cardiopulmonary bypass (CPB), and leads to significant morbidity, mortality, and cost. Although early recognition and management of AKI may reduce the burden of renal disease, reliance on serum creatinine accumulation to confidently diagnose it leads to a significant and important delay (up to 48 hours). Hence, a search for earlier AKI biomarkers is warranted. The renal-resistive index (RRI) is a promising early AKI biomarker that reflects intrarenal arterial pulsatility as reflected by the peak systolic and end-diastolic blood velocities divided by the peak systolic velocity. During cardiac surgery, post-CPB elevation of RRI is correlated with renal injury. The RRI is influenced by intrarenal and extrarenal factors, as well as different hemodynamic states. Understanding its limitations may increase its usefulness as an early AKI biomarker. For example, tachycardia or aortic stenosis typically results in a lower RRI, whereas bradycardia or increased systemic pulse pressure (as seen with aortic insufficiency) are associated with a higher RRI, unrelated to any intrarenal effects. In this E-Challenge, the authors present two cases in which the RRI was used to evaluate a patient's risk of developing AKI.

Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer.

Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM-1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM-1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0-13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, -0.33). Urine platinum was not associated with postinfusion AKIor KIM-1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.

Neutrophil gelatinase-associated lipocalin as a biomarker for predicting acute kidney injury after coronary artery bypass grafting

BackgroundEarly and precocious determination of acute kidney injury (AKI) is essential to prevent morbidity and mortality following coronary artery bypass grafting (CABG). Evaluation of the perioperative renal function is substantial using novel biomarkers other than the late traditional method of using serum creatinine. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker investigated for early detection of AKI in patients undergoing coronary artery bypass grafting, and its role has to be determined in this study.ResultsTwenty-five patients undergoing elective CABG were enrolled in this cohort study and were assigned into two groups: group I include the patients that did not develop AKI (no AKI group) and group II include the patients that developed AKI (AKI group). Acute kidney injury based on Kidney Disease: Improving Global Outcomes (KDIGO) classification had been developed in 7 patients (28%). Plasma NGAL levels at 6 h were higher in patients who developed AKI compared with those who did not (302 ± 88.02 vs. 116.50 ± 17.33 ng/m, p value < 0.001). The cut-off value of plasma NGAL levels measured 6 h postoperatively was 145 ng/ml and the area under the receiver-operating characteristic (ROC) curve was 0.965. Results of this study showed that plasma NGAL is a robust early biomarker of AKI, which preceded the rise in serum creatinine by many hours.ConclusionThis study revealed that earlier diagnosis of acute kidney injury in patients undergoing CABG can be achieved by measuring postoperative plasma NGAL concentration at 6 h.

Increase of urinary TIMP-2 and IGFBP7 as potential predictor of acute kidney injury requiring renal replacement therapy and patients' outcome following complex endovascular and open thoracic abdominal aortic aneurysm surgery - a prospective observational study.

Background: Acute kidney injury (AKI) as complication after open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is one major predictor of mortality and postoperative complications. We evaluated tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as combined early biomarker for AKI detection and predictor of patients' outcome. Patients and methods: Between 2014 and 2015, 52 patients have been enrolled in this observational study, of whom 29 (55.8%) underwent elective open repair and 23 (44.2%) endovascular repair. TIMP2×IGFBP7 were measured until 48 hours after admission on intensive-care unit (ICU) and were analyzed regarding their predictive ability for AKI (defined according to the KDIGO criteria) requiring temporary renal replacement therapy (RRT) and 90-day mortality using ROC curves. Results: Mean patient age was 64.5 years (Min: 43, Max: 85), endovascular treated patients were older (p <0.0001). 40.4% (n = 21) developed AKI, and 21.2% (n = 11) required renal replacement therapy. In-hospital and total mortality rates were 7.7% (n = 4) and 9.6% (n = 5), respectively. At no time a significant difference in TIMP2×IGFB7 levels between patients undergoing open or endovascular surgery was observed. The predictive quality of the TIMP2×IGFBP7 value on ICU admission was sound regarding AKI requiring temporary renal replacement therapy (sensitivity: 55.56% [38.1-72.1%], specificity: 90.91% [58.7-99.8%] with an area under the curve [AUC]: 0.694 [0.543-0.820]). Mean follow-up was 13.2 months (Min: 2, Max: 20), regarding the 90-day mortality, the predictive property of the TIMP2×IGFBP7 value was not sufficient (sensitivity: 80% [28.4-99.5%], specificity: 52.38% [36.4-68%], and AUC: 0.607 [0.454-0.746]). Conclusions: TIMP2×IGFBP7 level measured 6-12 hrs postoperatively may be useful as an early detectable biomarker for AKI requiring temporary renal replacement therapy. It seems not suited to predict patients' outcome following complex thoracoabdominal aortic surgery, regardless if performed by open or endovascular repair.

Plasma cystatin C versus renal resistive index as early predictors of acute kidney injury in critically ill neonates

Acute kidney injury (AKI) independently predicts morbidity and mortality of critically ill neonates. Serum cystatin C is a promising early biomarker for AKI. Evaluating the renal resistive index (RRI) by Doppler ultrasound demonstrates abnormal intrarenal vascular impendence. The objective of this study was to compare the ability of plasma cystatin C and the RRIto predict AKI early in critically ill neonates. Sixty critically ill neonates in neonatal intensive care units were assigned to three groups: group 1 (cases) of thirty participants fulfilling the AKI diagnostic criteria of neonatal Kidney Disease Improving Global Outcome, group 2 of thirty participants not fulfilling the criteria, as well as the 3rd group of thirty age- and sex-matching healthy participants. Group 1 demonstrated a significantly high mean cystatin C level during the 1st day of incubation compared with the other two groups [group 1 (3.18±1.25), group 2 (1.68±0.66), and group 3 (0.80±0.26)]. Serum creatinine and RRI were insignificantly different among all groups. At a cutoff value of 2.68 (mg/l), cystatin C level had significantly higher area under the curve (AUC) (0.804) than both serum creatinine (0.453) and RRI (0.551) and had 53.3% sensitivity and 100% specificity in the early prediction of neonates with AKI. The RRI had a lower non-significant AUC(0.551) at a cutoff value of 0.53 and had 100% sensitivity and 40% specificity, while serum creatinine had a low non-significant AUC(0.453) at a cutoff value of 0.49 (mg/dl) and had 33.3%sensitivity and 86.7%specificity. Applying regression analysis to predict AKI in critically ill neonates as early as possible, higher plasma cystatin C and lower estimated glomerular filtration rate cystatin were the only independent risk factors within critically ill neonates. The level of plasma cystatin C increased 48h before both RRI and serum creatinine did in critically ill neonates who developed AKI, soit is more reliable in predicting AKI in critically ill neonates than serum creatinine and RRI.

Intraoperative renal resistive index threshold as an acute kidney injury biomarker.

The lag in creatinine-mediated diagnosis of cardiac surgery-associated acute kidney injury (AKI) may be impeding the development of renoprotection therapies. Postoperative renal resistive index (RRI) measured by transabdominal Doppler ultrasound is a promising early AKI biomarker. RRI measured intraoperatively by transesophageal echocardiography (TEE) is available even earlier but is less evaluated. Therefore, we conducted an assessment of intraoperative RRI as an AKI biomarker using previously reported post-renal insult thresholds. Retrospective convenience sample. Intraoperative. 180 adult cardiac surgical patients between July 2013 and July 2014. None. Pre- and post-cardiopulmonary bypass (CPB) RRI thresholds, measured using intraoperative TEE, exceeding 0.74 or 0.79 were used to evaluate for an association with KDIGO AKI risk using the Chi-square test. Other consensus AKI criteria (AKIN, RIFLE) were similarly evaluated. Additional t-test analyses examined the relationship of pre- and pre-to-post (delta) CPB RRI with AKI. Post-CPB RRI for 99 patients included 36 and 23 with values exceeding 0.74 and 0.79, respectively. Analyses confirmed associations of both RRI thresholds with all consensus AKI definitions (0.74; KDIGO: p = 0.05, AKIN: p = 0.03, RIFLE: p = 0.03, 0.79; KDIGO: p = 0.002, AKIN: p = 0.001, RIFLE: p = 0.004). In contrast, pre-CPB and pre-to post-CPB RRI were not associated with AKI. RRI obtained intraoperatively in cardiac surgery patients, assessed using previously reported thresholds, is highly associated with AKI and warrants further evaluation as a promising "earliest" AKI biomarker. These significant findings suggest that RRI assessment should be included in the standard intraoperative TEE exam.

Early Diagnosis and Prognostic Value of Acute Kidney Injury in Critically Ill Patients.

Background and objectives: In hospitalized children, acute kidney injury (AKI) remains to be a frequent and serious condition, associated with increased patient mortality and morbidity. Identifying early biomarkers of AKI and patient groups at the risk of developing AKI is of crucial importance in current clinical practice. Specific human protein urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 18 (uIL-18) levels have been reported to peak specifically at the early stages of AKI before a rise in serum creatinine (sCr). Therefore, the aim of our study was to determine changes in uNGAL and uIL-18 levels among critically ill children and to identify the patient groups at the highest risk of developing AKI. Materials and methods: This single-center prospective observational study included 107 critically ill children aged from 1 month to 18 years, who were treated in the Pediatric Intensive Care Unit (PICU) of Lithuanian University of Health Sciences Hospital Kauno Klinikos from 1 December 2013, to 30 November 2016. The patients were divided into two groups: those who did not develop AKI (Group 1) and those who developed AKI (Group 2). Results: A total of 68 (63.6%) boys and 39 (36.4%) girls were enrolled in the study. The mean age of the patients was 101.30 ± 75.90 months. The mean length of stay in PICU and hospital was 7.91 ± 11.07 and 31.29 ± 39.09 days, respectively. A total of 32 (29.9%) children developed AKI. Of them, 29 (90.6%) cases of AKI were documented within the first three days from admission to hospital. In all cases, AKI was caused by diseases of non-renal origin. There was a significant association between the uNGAL level and AKI between Groups 1 and 2 both on day 1 (p = 0.04) and day 3 (p = 0.018). Differences in uNGAL normalized to creatinine in the urine (uCr) (uNGAL/uCr) between the groups on days 1 and 3 were also statistically significant (p = 0.007 and p = 0.015, respectively). uNGAL was found to be a good prognostic marker. No significant associations between uIL-18 or Uil-18/uCr and development of AKI were found. However, the uIL-18 level of >69.24 pg/mL during the first 24 h was associated with an eightfold greater risk of AKI progression (OR = 8.33, 95% CI = 1.39–49.87, p = 0.023). The AUC for uIL-18 was 73.4% with a sensitivity of 62.59% and a specificity of 83.3%. Age of <20 months, Pediatric Index of Mortality 2 (PIM2) score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of three and more organ systems, PICU length of stay more than three days, and length of mechanical ventilation of >five days were associated with a greater risk of developing AKI. Conclusions: Significant risk factors for AKI were age of <20 months, PIM2 score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of 3 and more organ systems, PICU length of stay of more than three days, and length of mechanical ventilation of > five days. uNGAL was identified as a good prognostic marker of AKI. On admission to PICU, uNGAL should be measured within the first three days in patients at the risk of developing AKI. The uIL-18 level on the first day was found to be as a biomarker predicting the progression of AKI.

Urine klotho is a potential early biomarker for acute kidney injury and associated with poor renal outcome after cardiac surgery

BackgroundCurrent paradigms of detecting acute kidney injury (AKI) are insensitive and non-specific. Klotho is a pleiotropic protein that is predominantly expressed in renal tubules. In this study, we evaluated the diagnostic and prognostic roles of urine Klotho for AKI following cardiac surgery.MethodsWe conducted a prospective study involving 91 patients undergoing cardiac surgery. AKI was defined according to the AKIN definition. The renal outcomes within 7 days after operation were evaluated. Perioperative levels of urine Klotho and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured by using ELISA.ResultsOf 91 participants, 33 patients (36.26%) developed AKI. Of these AKI patients, 21 (63.64%), 8 (24.24%), and 4 (12.12%) were staged 1, 2, and 3, respectively. Serum creatinine in AKI patients began to slightly increase at first postoperative time and reached the AKI diagnostic value 1 day after operation.Postoperative urine Klotho peaked at the first postoperative time (0 h after admission to the intensive care unit (ICU)) in patients with AKI, and was higher than that in non-AKI patients up to day 3. The AUC of detecting AKI for urine Klotho was higher than urine NGAL at the first postoperative time and 4 h after admission to the ICU. In a multivariate model, increased first postoperative urine Klotho may be an independent predictor for AKI occurrence following cardiac surgery. The concentrations of first postoperative urine Klotho were higher in AKI stage 2 and 3 than those in stage 1 (p < 0.05), and were higher in patients with incomplete recovery of renal function than those with complete recovery (p < 0.05).ConclusionsUrine Klotho may serve as an early biomarker for AKI and subsequent poor short-term renal outcome in patients undergoing cardiac surgery.

SAT-132 CIRCULATING MICRORNAS DETECT ACUTE KIDNEY INJURY FOLLOWING INGESTION OF POTASSIUM PERMANGANATE AND OXALIC ACID

Early detection of acute kidney injury (AKI) is difficult due to the lack of sensitive and specific biomarkers. MicroRNAs are stable biomarkers, which are released following cellular injury. Local and systemic effects of tissue injury can be captured via efficient detection of microRNAs in bio-fluids. This study aims to identify a signature of serum microRNAs as early biomarkers of AKI in patients following poisoning with oxalic acid and potassium permanganate.

Urinary Biomarkers of Acute Kidney Injury in Pediatric Stem Cell Transplantation

Novel Urinary Biomarkers of Early Acute Kidney Injury in Pediatric Stem Cell Transplantation Acute kidney injury (AKI) is a common complication in pediatric stem cell transplantation (SCT). Creatinine is a late biomarker of AKI. Several novel urinary biomarkers that predict AKI have been proposed. We evaluated the sequential patterns of biomarker elevation after SCT to determine their diagnostic accuracy. We measured urine neutrophil gelatinase associated lipocalin (NGAL), monocyte chemoattractant protein 1 (MCP1), kidney injury molecule 1 (KIM1), vitamin D binding protein (VDBP), and albumin using urine prospectively collected from consecutive pediatric allogeneic SCT patients at baseline and days 0, 14, and 28 using commercial ELISA assays validated for use with urine. Association of AKI (≥50% increase in serum creatinine from baseline) in the first 28 days of HSCT with patient, primary disease, and SCT characteristics was assessed (Table 1), for which only exposure to chemotherapy prior to SCT was significant. We then analyzed the association between each biomarker with the clinical outcome of AKI in the first 28 days of SCT. Of the 80 patients examined, AKI developed in 18 patients. Elevations of MCP1 and NGAL at day 14, and elevations in MCP1 and KIM1 at day 28 were significantly higher in patients who developed AKI (Figure 1). Albuminuria, the most traditional urinary biomarker, showed no discriminating ability. MCP1, KIM1, and NGAL are promising novel biomarkers of early AKI in SCT. Urinary biomarkers could improve renal outcomes in stem cell transplantation by enabling earlier identification of acute kidney injury.

Diagnostic Utility of Serum Neutrophil Gelatinase-Associated Lipocalin in Polytraumatized Patients Suffering Acute Kidney Injury: A Prospective Study

Introduction The incidence of acute kidney injury (AKI) considerably increases the mortality rate in polytrauma victims. Undoubtedly, early identification of patients at risk is crucial for timely implementation of preventive strategies in order to improve their prognosis. Therefore, we aimed to investigate if serum neutrophil gelatinase-associated lipocalin (sNGAL) may serve as a diagnostic biomarker of early AKI in polytrauma victims, especially considering patients needing renal replacement theory (RRT). Material and Methods Forty consecutive polytrauma victims (ISS ≥ 16, AISThorax ≥ 1, age ≥ 18 years, survival time ≥ 48 hours), directly admitted to our level I trauma center within one posttraumatic hour, were enrolled in our prospective study. sNGAL-levels were assessed at admission (initial) and on day 2 after trauma. AKI was diagnosed by an increase of serum creatinine (sCr) level of at least 0.3 mg/dl within 48 hours. Results Out of 30 men and 10 women (mean age, 43 years; mean ISS, 29), seven patients developed AKI, four of them needing RRT. AKI was diagnosed in 86% of the affected individuals until day 2. Day2-sNGAL-levels were higher in the AKI-group, compared to the no-AKI-group (p=0.049), and in patients treated with RRT than in individuals not needing RRT (p=0.037). Noteworthy, in patients not needing RRT sNGAL-levels significantly decreased from initial to day2-measurement (p=0.040). Furthermore, at any time point during our observation period polytraumatized patients with AKI and day2-sNGAL-levels of at least 181.0 ng/mL presented with higher sCr-levels compared to polytraumatized patients without AKI and day2-sNGAL-levels lower than 181.0 ng/mL (p≤0.029). Conclusion In polytrauma victims suffering AKI an increase in sNGAL-level from initial to day2-assessment may signalize deterioration in kidney function and thus indicate AKI progression. Unlike initial sNGAL-levels day2-sNGAL-levels might be an appropriate tool to define AKI and to signify the need of RRT in polytraumatized patients.