Biomarkers Neutrophil Gelatinase-associated Lipocalin Research Articles

S1824 A Diagnostic Study of Urine Biomarkers Neutrophil Gelatinase-Associated Lipocalin (uNGAL) and Urine Interleukin-18 (uIL-18) in Diagnosis of Acute Kidney Injury in Liver Cirrhosis

S1824 A Diagnostic Study of Urine Biomarkers Neutrophil Gelatinase-Associated Lipocalin (uNGAL) and Urine Interleukin-18 (uIL-18) in Diagnosis of Acute Kidney Injury in Liver Cirrhosis

Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy.

Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined. In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02). Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.

Comparison of Urinary Biomarkers in Diagnosis of Ureteropelvic Junction Obstruction and Differentiation from Nonobstructive Dilatation.

Differentiation of nonobstructive dilatation (NOD) from ureteropelvic junction obstruction (UPJO) is a challenge in children with antenatally detected hydronephrosis. The aim of this study is to compare the utility of urinary biomarkers: carbohydrate antigen (CA 19-9), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM) in diagnosing UPJO. A prospective study was conducted after obtaining ethical clearance between 2021 and 2022. Group 1 - control group (n = 30): children with normal antenatal ultrasound with no urinary symptoms. Group 2 - study group (n = 48): children with unilateral hydronephrosis: Group 2a - NOD (n = 24): children stable on ultrasound and diuretic renogram and Group 2b - UPJO (n = 24): children who worsened to Grade 4 hydronephrosis on ultrasound/worsening of differential renal function (10% drop) on renogram who underwent pyeloplasty. Urinary biomarkers NGAL, KIM-1, and CA 19-9 were measured using the enzyme-linked immune absorbent assay method. The urine CA 19-9 level was 128.05 ± 4.08 U/mL in the UPJO group, and this was significantly higher (P = 0.001) than NOD, 70.29 ± 4.41, and controls, 1.91 ± 1.57. The urine NGAL level was 21.41 ± 4.44 pg/mL in UPJO, and this was significantly higher than controls, 2.669 ± 0.513, but not NOD, 24.55 ± 2.67. The urine KIM level was 817 ± 15.84 pg/mL in the UPJO group, and this was significantly higher than controls, 285 ± 8.10, but not NOD, 768.23 ± 15.12. Receiver operating characteristic analysis of CA 19-9 revealed a urine biomarker cutoff of 95 U/mL for diagnosing UPJO (sensitivity 95%; specificity 96%; and area under the curve 0.99). CA 19-9 is a superior marker compared to NGAL and KIM in differentiating UPJO from NOD. Further studies with larger numbers are warranted.

Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs

BackgroundCurrent diagnoses of urinary tract infection (UTI) by standard urine culture (SUC) has significant limitations in sensitivity, especially for fastidious organisms, and the ability to identify organisms in polymicrobial infections. The significant rate of both SUC “negative” or “mixed flora/contamination” results in UTI cases and the high prevalence of asymptomatic bacteriuria indicate the need for an accurate diagnostic test to help identify true UTI cases. This study aimed to determine if infection-associated urinary biomarkers can differentiate definitive UTI cases from non-UTI controls.MethodsMidstream clean-catch voided urine samples were collected from asymptomatic volunteers and symptomatic subjects ≥ 60 years old diagnosed with a UTI in a urology specialty setting. Microbial identification and density were assessed using a multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and SUC. Three biomarkers [neutrophil gelatinase-associated lipocalin (NGAL), and Interleukins 8 and 1β (IL-8, and IL-1β)] were also measured via enzyme-linked immunosorbent assay (ELISA). Definitive UTI cases were defined as symptomatic subjects with a UTI diagnosis and positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were defined as asymptomatic volunteers.ResultsWe observed a strong positive correlation (R2 > 0.90; p < 0.0001) between microbial density and the biomarkers NGAL, IL-8, and IL-1β for symptomatic subjects. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 84.0%, specificity 91.2%, positive predictive value 93.7%, negative predictive value 78.8%, accuracy 86.9%, positive likelihood ratio of 9.58, and negative likelihood ratio of 0.17 in differentiating definitive UTI from non-UTI cases, regardless of non-zero microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.ConclusionWe demonstrated that positive infection-associated urinary biomarkers NGAL, IL-8, and IL-1β, in symptomatic subjects with positive SUC and/or M-PCR results was associated with definitive UTI cases. A consensus criterion with ≥ 2 of the biomarkers meeting the positivity thresholds showed a good balance of sensitivity (84.0%), specificity (91.2%), and accuracy (86.9%). Therefore, this biomarker consensus is an excellent supportive diagnostic tool for resolving the presence of active UTI, particularly if SUC and M-PCR results disagree.

Real-Time Acute Kidney Injury Risk Stratification–Biomarker Directed Fluid Management Improves Outcomes in Critically Ill Children and Young Adults

Critically ill admitted patients are at high risk of acute kidney injury (AKI). The renal angina index (RAI) and urinary biomarker neutrophil gelatinase-associated lipocalin (uNGAL) can aid in AKI risk assessment. We implemented the Trial in AKI using NGAL and Fluid Overload to optimize CRRT Use (TAKING FOCUS 2; TF2) to personalize fluid management and continuous renal replacement therapy (CRRT) initiation based on AKI risk and patient fluid accumulation. We compared outcomes pre-TF2 and post-TF2 initiation. Patients admitted from July 2017 were followed-up prospectively with the following: (i) an automated RAI result at 12 hours of admission, (ii) a conditional uNGAL order for RAI≥8, and (iii) a CRRT initiation goal at 10% to 15% weight-based fluid accumulation. A total of 286 patients comprised 304 intensive care unit (ICU) RAI+ admissions; 178 patients received CRRT over the observation period (2014-2021). Median time from ICU admission to CRRT initiation was 2 days shorter (P< 0.002), and≥15% pre-CRRT fluid accumulation rate was lower in the TF2 era (P< 0.02). TF2 ICU length of stay (LOS) after CRRT discontinuation and total ICU LOS were 6 and 11 days shorter for CRRT survivors (both P< 0.02). Survival rates to ICU discharge after CRRT discontinuation were higher in the TF2 era (P= 0.001). These associations persisted in each TF2 year; we estimate a conservative $12,500 health care cost savings per CRRT patient treated after TF2 implementation. We suggest that automated clinical decision support (CDS) combining risk stratification and AKI biomarker assessment can produce durable reductions in pediatric CRRT patient morbidity.

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic UTI patients aged ≥ 60 years and correlated them with detected levels of the immune response biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β). The objective was to identify the microbial densities associated with significant elevation of these biomarkers in order to determine an optimal threshold for diagnosing symptomatic UTIs. Biobanked midstream voided urine samples were analyzed for microbial identification and quantification using standard urine culture (SUC) and multiplex-polymerase chain reaction (M-PCR) testing, while NGAL, IL-8, and IL-1β levels were measured via enzyme-linked immunosorbent assay (ELISA). NGAL, IL-8, and IL-1β levels were all significantly elevated at microbial densities ≥ 10,000 cells/mL when measured via M-PCR (p < 0.0069) or equivalent colony-forming units (CFUs)/mL via SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable than 100,000 CFU/mL for diagnosing UTIs.

Comparative Analysis of HtrA3 and NGAL as Viable Biomarkers for Pre-eclampsia

Pre-eclampsia is a pregnancy-associated condition, which is characterized by the onset of hypertension and proteinuria. It is one of the leading causes of maternal and neonatal mortality and this affliction has been recorded in around 8% of all pregnancies in the world. In addition to this, the etiopathology of this condition is very less understood and the resources available to diagnose and treat it are limited. Prior studies suggest more than a hundred possible diagnostic biomarkers that could be used to detect this disease early on. However, most of them are not feasible due to several reasons including stability, cost, safety, etc. Here two biomarkers HtrA3 (high-temperature requirement A3) and NGAL (Neutrophil Gelatinase Associated Lipocalin) are selected for the detection of pre-eclampsia, and we compare their efficacy in the detection of pre-eclampsia based on their specificity, ease of use, speed, stage of detection and source (invasiveness). We found that these two biomarkers are efficient under some parameters, and inefficient under others. The scoring system used in the current study suggests that NGAL is a superior biomarker. The results of this study help to develop a stronger understanding of both these biomarkers in the short and long term to classify the biomarkers more efficiently and understand the complicated pathologies of pre-eclampsia.

#6535 SEXUAL DIMORPHISMS OF ACUTE KIDNEY INJURY: DIVERGENT PERFORMANCES OF BIOMARKERS OR DIFFERENT MOLECULAR MECHANISMS?

Abstract Background and Aims Before implementing individualized strategies to prevent or treat acute kidney injury (AKI), identifying clusters of patients with common (or divergent) pathophysiological mechanisms, diagnosis criteria or outcome is of upmost importance. Method We compared the characteristics of 1170 male and female patients referred for cardiac surgery with cardiac bypass (CBP) using multivariate logistic regression and propension score-based analysis. Performances of the candidate urinary biomarkers neutrophil gelatinase-associated lipocalin (uNGAL), [IGFBP7].[TIMP-2] product (Nephrocheck), and a recently developed AKI signature of 204 urinary peptides (PeptAKI) were compared, and sex-dependent individual urinary peptide changes were studied. Results In these patients referred for CBP-surgery, incidence and severity (K/DIGO classification) of AKI were similar in men and women (about 25%), even after adjustment of the usual risk factors of AKI including baseline estimated glomerular filtration rate, age, diabetes mellitus, length of CBP and red blood cell transfusion. Performances of uNGAL, Nephrocheck and PeptAKI strongly diverged between males and females. In the overall cohort, as well as in sub-groups of males and females, the multi-markers PeptAKI signature outperformed uNGAL and NephroCheck. Reanalysis of peptides included in PeptAKI at the single peptide level suggested divergences of AKI mechanisms between sexes. In women, the peptide score-derived risk of AKI strongly relied on peptides indicating kidney inflammation (including SERPINs, SAA1, osteopontin, uromodulin fragments) and hemolysis (HBA1, HBB), whereas a peptide derived from a stress-responsive protective gene in kidney tubular epithelial cells (VGF nerve growth factor) was dramatically less abundant in women developing AKI. Conclusion In patients referred for CBP-surgery, significant clinical and biological differences between men and women, as well as sexual dimorphism of AKI biomarkers performances, were identified. Urinary peptide signatures may help to personalize prevention of AKI progression by giving both quantitative and sex-related qualitative information on molecular mechanisms underlying AKI.

Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress

To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS). A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope. Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05). Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.

NGAL as Biomarker of Clinical and Subclinical Damage of Kidney Function after Coronary Angiography.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study, we investigate the clinical use in these directions of a "damage"-type biomarker-neutrophil gelatinase-associated lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasma NGAL was determined at baseline and at 4th and 24th h after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (Me 109.3 (IQR 92.1-148.7) ng/mL versus 97.6 (IQR 69.4-127.0) ng/mL, p = 0.006) and at the 24th hour (Me 131.0 (IQR 81.1-240.8) ng/mL, p = 0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (Me 94.0 (IQR 75.5-148.2) ng/mL, p = 0.002) and reached levels close to those in patients with CI-AKI. Unlike the new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good-AUC 0.847 (95% CI: 0.677-1.000; p = 0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539-0.924; p = 0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for the early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.

THE DIAGNOSTIC VALUE OF URINE GELATINASE-ASSOCIATED LIPOCALIN AS A BIOMARKER FOR ACUTE KIDNEY INJURY IN PRETERM INFANTS WITH HEMODYNAMICALLY SIGNIFICANT PATENT DUCTUS ARTERIOSUS

THE DIAGNOSTIC VALUE OF URINE GELATINASE-ASSOCIATED LIPOCALIN AS A BIOMARKER FOR ACUTE KIDNEY INJURY IN PRETERM INFANTS WITH HEMODYNAMICALLY SIGNIFICANT PATENT DUCTUS ARTERIOSUS

Abstract 125: Kidney-specific Biomarkers For Predicting Acute Kidney Injury Following Cardiac Arrest

Introduction: Acute kidney injury (AKI) is a common complication following cardiac arrest (CA) and is associated with poor outcomes. Early detection of AKI is crucial; serum creatinine (sCR) is the most commonly used indicator of AKI, despite low sensitivity and specificity for early detection of AKI. Hypothesis: Kidney-specific serum biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C could better predict post-CA AKI than sCR. Methods: Adult CA patients who had kidney-specific biomarkers of AKI collected shortly after return of spontaneous circulation (ROSC) as part of four randomized trials and one observational study were included. Patients with Kidney Disease Improving Global Outcome (KDIGO) stage III AKI or end-stage renal disease, or renal replacement therapy at the time of enrollment were excluded. The association between renal biomarker levels (sCR, NGAL, KIM-1, cystatin-C) shortly after ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development. Results: Of 155 patients, 46 (29.7%) developed stage III AKI within 7 days, and 98 (63.2%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of sCR (1.4 mg/dL [IQR: 1.2, 1.9] vs. 1.2 [IQR: 1.0, 1.5]; p=0.001), NGAL (868,208 pg/mL [IQR: 412,547.1, 1,341,597] vs. 298,928.3 [IQR: 170,786.6, 594,389.7], p&lt;0.001). and cystatin-C (1,649,202 pg/mL [IQR: 1,184,788, 2,440,583] vs. 1,132,955 [IQR: 795,323.7, 1,580,415]; p&lt;0.001). There was no difference in KIM-1 between groups (150.6 pg/mL [IQR: 150.8, 288.4] vs. 158.9 [IQR: 78.8, 284.7]; p=0.351). There was no significant difference between biomarkers in their ability to predict development of stage III AKI (NGAL AUC=0.75 [95%CI: 0.67-0.83], cystatin-C AUC=0.71 [95%CI: 0.62-0.79], KIM-1 AUC=0.55 [95%CI: 0.45-0.65], sCR AUC=0.67 [95%CI: 0.57-0.76], p&gt;0.05 for all). Both NGAL and cystatin-C performed better than KIM-1 (p&lt;0.01). Conclusion: In post-CA patients, sCR, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to sCR. Comparison was limited by the small number of patients who developed AKI.

Comparison of Biomarkers to Differentiate Chronic Kidney Disease and Chronic Kidney Disease of Unknown Etiology

Chronic kidney disease of unknown etiology (CKDU) is prevalent and clinically silent until its late stages at which patient may suffer significant irreversible damage, or mortality in the absence of early screening and intervention. CKDU is asymptomatic but may show nonspecific symptoms. Conventional markers are influenced by multiple non-renal factors while Kidney injury molecule-1(KIM-1) and Neutrophil gelatinase-associated lipocalin(NGAL) are promising biomarkers of chronic kidney disease (CKD), there are no studies reported so far on these markers in CKDU. The aim of the study is to assess the sensitivity of biomarkers serum KIM-1 and NGAL in patients with CKDU in comparison with CKD and controls. To achieve this, our objectives are to estimate the level of biochemical parameters like serum creatinine, urea, uric acid, random blood sugar, systolic and diastolic blood pressure and hemoglobin and to compare novel biomarkers KIM-1 and NGAL in CKDU patients with CKD. The serum levels of urea, uric acid, creatinine, KIM-1 and NGAL were estimated in control, CKD and CKDU (n = 35, 46, 79 respectively). Creatinine showed 8.1-fold and 2.7-fold increase (P &lt;0.001), and urea 4.0% and 1.8% increase (P &lt; 0.001), compared to control in CKD and CKDU cohorts, respectively. The sensitivity and specificity of KIM-1 was 73.4% and 67.4%with a cutoff value of 203.5ng/mL using the receiver operating characteristic(ROC) curve. For NGAL they were 82.3%, 73.9% and 255ng/mL. Compared to control, KIM-1 showed a 51.5-fold and 87.2-fold increase in CKD and CKDU, respectively (P &lt; 0.001). NGAL showed a 4.8-fold and 6.7-fold increase in CKD and CKDU, respectively (P &lt; 0.001). Creatinine and urea were higher in CKD than in CKDU, whereas KIM-1 and NGAL were higher in CKDU than CKD. KIM-1 and NGAL are sensitive biomarkers for CKDU. KIM-1 can differentiate CKD and CKDU.&#x0D;

Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes.

Early identification of youth with type 1 diabetes (T1D) at risk for diabetic kidney disease may improve clinical outcomes. We examined the cross-sectional relationship between kidney biomarkers neutrophil gelatinase-associated lipocalin (NGAL), copeptin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), chitinase-3-like protein-1 (YKL-40), and monocyte chemoattractant protein-1 (MCP-1) and intrarenal hemodynamic function in adolescents with T1D. Urine albumin-to-creatinine ratio (UACR), renal vascular resistance (RVR), glomerular filtration rate (GFR), intraglomerular pressure (PGLO), efferent arteriole resistance (RE), afferent arteriolar resistance (RA), and renal plasma flow (RPF), and the above indicated biomarkers were assessed in youth aged 12-21years with and without T1D of < 10years duration. Fifty adolescents with T1D (16.1 ± 3.0years, HbA1c 8.6 ± 1.2%) and 20 adolescents of comparable BMI without T1D (16.1 ± 2.9years, HbA1c 5.2 ± 0.2%) were enrolled. Adolescents with T1D demonstrated significantly higher GFR, RPF, RE, and PGLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and RA than controls (25% and 155%, respectively, both p < 0.0001). YKL-40 and KIM-1 concentrations, respectively, were positively associated with GFR (r: 0.43, p = 0.002; r: 0.41, p = 0.003), RPF (r: 0.29, p = 0.08; r: 0.34, p = 0.04), UACR (r: 0.33, p = 0.02; r: 0.50, p = 0.0002), and PGLO (r: 0.45, p = 0.006; r: 0.52, p = 0.001) in adolescents with T1D. Higher concentrations of biomarkers YKL-40 and KIM-1 may help define the risk for intraglomerular hemodynamic dysfunction in youth with T1D. A higher resolution version of the Graphical abstract is available as Supplementary information.

Impact of retrograde intrarenal surgery on biomarkers that are associated with renal parenchyma injury, a preliminary study.

The primary objective of this preliminary study was to assess the changes in concentration of biomarkers, which indicate renal injury, after RIRS. Within this prospective study, we included 21 patients with nephrolithiasis requiring treatment with RIRS. From each patient, blood and urine samples were taken at fixed intervals before and after RIRS. Kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), calbindin, albumin, clusterin, gluthation S-transferase-π (GST-π), beta-2-microglobulin (B2M), osteopontin, cystatin c, and trefoil-factor-3 (TFF3) were measured in urine. Creatinine, cystatin c and uric acid were analyzed in the blood samples. A significant increase of the biomarkers clusterin, GST-π, B2M, NGAL and cystatin c was observed after RIRS. However, the biomarkers gradually normalized during the first 14 postoperative days. The parameters surgery time, cumulative stone volume, and BMI did not significantly influence the biomarker concentrations. In the case of GST-π and NGAL a significant positive, yet minuscule effect of age was observed. With our study, we identified 5 out of 12 assessed renal injury biomarkers that showed a significant increase after RIRS. The increase was only temporary and all markers normalized within 14days. Further studies are needed to determine the clinical value of these identified markers to assess the long-term impact of intrarenal pressure elevation during RIRS.

Utility of Urinary Biomarkers Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as a Marker for Diagnosing the Presence of Renal Scar in Children with Vesicoureteral Reflux (VUR): A Cross-Sectional Study.

Aim:To explore the possibility of using urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assess the presence of renal scars in children with Vesicoureteric Reflux (VUR).Materials and Methods:This cross-sectional study was conducted in 94 children aged 0–16 years diagnosed with VUR in the Department of Pediatric Surgery, JIPMER. Urinary biomarkers were measured using the enzyme-linked immunosorbent assay kits, normalized with urinary creatinine (Cr) and compared with severity of VUR (low grade [I and II] and high grade [III, IV, and V]), presence or absence of renal scar in VUR patients and severity of renal scar. Independent Student's t-test, Mann–Whitney U-test, and analysis of variance Kruskal–Wallis test were used for comparison, and receiver operating characteristic (ROC) curve analysis for predicting the accuracy of biomarkers in detecting the presence of renal scars.Results:The median urinary NGAL (uNGAL) value was higher in children with renal scar (1.49 ng/mL) than those without renal scar (0.58 ng/mL) and was statistically significant (<0.001). Whereas median uNGAL/Cr was higher in children with renal scar (0.07) than those without renal scar (0.03) but was not statistically significant (P = 0.06). Urinary KIM-1 and urinary KIM-1/urinary Cr (uKIM-1/Cr) was not found to be a significant predictor of renal scar. The difference of uNGAL/Cr was comparable between the grades of renal scar but was not statistically significant. On ROC curve analysis, uNGAL had area under the ROC curve (AUC) of 0.769 with 71% of both specificity and sensitivity, whereas uNGAL/Cr was found to be a poor predictor of renal scar with AUC of 0.611, 60% sensitivity, and 61.2% specificity.Conclusion:uNGAL can serve as a noninvasive marker for diagnosing the presence of renal scar in children with VUR and a multicentric more extensive cohort study may be needed to strengthen or negate its role.

Biomarkers for the early prediction of contrast-induced nephropathy after percutaneous coronary intervention in adults: A systematic review and meta-analysis.

Contrast-induced nephropathy (CIN) is a complication of patients undergoing percutaneous coronary intervention (PCI). Promising biomarkers for the early prediction of CIN can significantly improve outcomes of these patients. We searched PubMed, EMBASE, Web of Science, and Cochrane Library for studies. Trials reporting an area under the curve (AUC) for the utility of novel biomarkers in the early prediction of CIN in adults after PCI were included. In total, 42 studies comprising 11,984 adult patients undergoing PCI met the criteria. Four urinary biomarkers and four blood biomarkers were included. For urine biomarkers, the pooled AUCs for neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) were 0.91 (95% CI 0.89-0.94), 0.79 (0.75-0.82), 0.78 (0.74-0.82), and 0.79 (0.76-0.83), respectively. The blood biomarkers NGAL, cystatin C, brain natriuretic peptide (BNP), and C-reactive protein (CRP) had pooled AUCs of 0.93 (0.91-0.95), 0.92 (0.89-0.94), 0.78 (0.74-0.81), and 0.75 (0.71-0.79), respectively. Subgroup analysis showed that blood NGAL in early CIN predictive time (<6 h) was more effective in predicting CIN. The efficiency of cystatin C in predicting CIN was reduced, whereas that of L-FABP was increased among chronic kidney disease (CKD) patients.

Urinary calprotectin, NGAL, and KIM-1 in the differentiation of primarily inflammatory vs. non-inflammatory stable chronic kidney diseases

Introduction It has been demonstrated that urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin are helpful biomarkers in the differentiation of intrinsic and prerenal acute kidney injury. Objective The present cross-sectional study investigates, whether urinary biomarkers are able to differentiate primarily inflammatory from non-inflammatory entities in chronic kidney disease (CKD). Methods Urinary calprotectin, NGAL, and kidney injury molecule-1 (KIM-1) concentrations were assessed in a study population of 143 patients with stable CKD and 29 healthy controls. Stable renal function was defined as an eGFR fluctuation ≤5 ml/min/1.73 m2 in the past 12 months. Pyuria, metastatic carcinoma, and renal transplantation were regarded as exclusion criteria. Diabetic nephropathy, hypertensive nephropathy, and polycystic kidney disease were categorized as ‘primarily non-inflammatory renal diseases’ (NIRD), whereas glomerulonephritis and vasculitis were regarded as ‘primarily inflammatory renal diseases’ (IRD). Results Urinary calprotectin and NGAL concentrations significantly differed between CKD and healthy controls (p < 0.05 each), whereas KIM-1 concentrations did not (p = 0.84). The three biomarkers did neither show significant differences in-between the individual entities, nor the two categories of IRD vs. NIRD (calprotectin 155.7 vs. 96.99 ng/ml; NGAL 14 896 vs. 11 977 pg/ml; KIM-1 1388 vs. 1009 pg/ml; p > 0.05 each). Albumin exceeds the diagnostic power of the investigated biomarkers by far. Conclusions The urinary biomarkers calprotectin, NGAL, and KIM-1 have no diagnostic value in the differentiation of primarily inflammatory vs. non-inflammatory etiologies of CKD.

Calprotectin and Neutrophil Gelatinase-Associated Lipocalin As Biomarkers of Acute Kidney Injury in Acute Coronary Syndrome

BackgroundAcute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients. Methods172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed. ResultsIn this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p < 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p < 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898. ConclusionsThis study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.

Biomarkers of kidney injury among children in a high-risk region for chronic kidney disease of uncertain etiology.

Mesoamerican Nephropathy (MeN), a form of chronic kidney disease of uncertain etiology, is a leading cause of death in Central America. The disease often presents in young adult male agricultural workers and progresses rapidly. Given the young age at presentation, we hypothesized that children in Central America experience subclinical kidney injury prior to working life. We assessed specimens from a cross-sectional study of youth, aged 7-17years, predominantly residing in a high-risk region of Nicaragua (n = 210). We evaluated urinary concentrations and risk factors for kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40). We evaluated the association between biomarkers and contemporaneous eGFR and compared biomarker concentrations with reference values from healthy children in other countries. Median uNGAL, uIL-18, and uKIM-1 concentrations exceeded healthy reference values. A one-year increase in age was associated with 40% increase in odds of being in the highest quartile of uNGAL (OR 1.4; (95%CI 1.2, 1.5); p < 0.0001). Youth who reported ever experiencing dysuria had 2.5 times the odds of having uNGAL concentrations in the top quartile (OR 2.5; (95%CI 1.4, 4.6); p = 0.003). Girls had significantly higher concentrations of all biomarkers than boys. Nine percent of children demonstrated low eGFR (≤ 100ml/min/1.73m2), while 29% showed evidence of hyperfiltration (eGFR ≥ 160ml/min/1.73m2), both potentially indicative of renal dysfunction. Children residing in regions of Nicaragua at high risk for MeN may experience subclinical kidney injury prior to occupational exposures.