Serial Measurements of Neutrophil Gelatinase-Associated Lipocalin levels for Assessment of Contrast Induced Nephropathy among Chronic Kidney Disease Patients Who Underwent Elective Coronary Angiography.

BACKGROUND: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI). OBJECTIVES: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI. METHODS: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI. RESULTS: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34-17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23-12.81, P = 0.06). CONCLUSIONS: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Assessment of Urinary Level of Neutrophil Gelatinaseassociated Lipocalin (NAGL) in Children with Renal Scar Due to Vesicoureteral Reflux.

INTRODUCTION: Renal scarring is a serious complications of urinary tract infection and vesicoureteral reflux (VUR). The dimercaptosuccinic acid (DMSA) scan is the gold standard method for diagnosing renal scars but is an expensive procedure that risks ionizing materials and is not available to everyone. Neutrophil gelatinase-associated lipocalin (NGAL) increases following inflammation, infection, and acute kidney injury in the urine. The aim of this study was to evaluate the urinary level of NGAL and determine its diagnostic value in renal scarring. METHODS: Patients aged 3 to 60 months with pyelonephritis were included in this study. Voiding cystourethrography (VCUG) was performed in the presence of hydronephrosis on ultrasonography. Children with VUR underwent DMSA scans six months after successful treatment of pyelonephritis., Patients were divided into two groups based on the result of DMSA scan: those with and those without renal scars. Levels of urinary NGAL were measured in both groups. RESULTS: Ninety-two children with VUR (grades 2 to 5) were studied, of whom 40 had renal scars and 52 did not. The urinary level of NGAL at the cutoff point of 284 ng/dL had 70% sensitivity and 100% specificity for the detection of renal scars and was higher in patients with renal scars. (P < .05). CONCLUSION: The urinary level of NGAL is considerably higher in children with renal scarring. It is not a good test for screening and early diagnosis due to its low sensitivity, although it can identify renal scars caused by VUR with high specificity.  DOI: 10.52547/ijkd.6951.

Balanced forced-diuresis compared to control as a reno-protective approach in cardiac surgery: secondary outcome of a randomized controlled trial, assessment of neutrophil gelatinase-associated lipocalin levels.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20-60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points. RESULTS: Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14-4.27, p = 0.02). CONCLUSIONS: Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946 .

Assessment of Serum and Urine Neurophil Gelatinase- Associated Lipocalin (s-NGAL and u-NGAL) Level as a Predictive Factor of Disease Progression in Diabetic Nephropathy in Type 2 DM.

INTRODUCTION: Diabetic nephropathy (DN) is a major complication of diabetes Mellitus. Early detection and intervention of DN can slow its progression and improve patients' outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubular damage might become a useful biomarker for the evaluation of renal involvement in diabetic patients. We aimed to evaluate the serum and urine NGAL(s-NGAL and u-NGAL) in type 2 diabetic patients and its correlation with different stages of diabetic nephropathy. METHODS: This cross-sectional study was designed on 198 subjects consisted of 50 controls and 148 type 2 diabetes patients (50 normoalbuminuric, 58 microalbuminuric, and 40 macroalbuminuric). The study was conducted with measuring s-NGAL and u-NGAL, albumin and spot urine creatinine were also measured. RESULTS: A highly increased level of s-NGAL was detected in macroalbuminuric group compared with controls, normoalbuminurics and microalbuminurics (P < .01). Highly raised u-NGAL levels were observed in macroalbuminurics in comparison with controls (P < .01). ROC curve demonstrated the best sensitivity and specificity of s-NGAL/u-NGAL for the macroalbuminuric state (sensitivity, 26% and 60%; specificity, 98% and 72%; respectively), in which the best cut-off points for the detection of macroalbuminuric state for s-NGAL/u-NGAL were 300 ng/mL and 71.4 ng/mL, respectively. CONCLUSION: Serum and urine-NGAL are elevated in type 2 diabetic patients, with or without albuminuria, s-NGAL level clearly correlates with severity of renal damage caused by DN and u-NGAL increases in macroalbuminuric state. S-NGAL could be a useful, noninvasive, available and practical test for evaluation of diabetic renal involvement. We could suggest u-NGAL as a probable predictor of macroalbuminuria.

Serum Beta-Trace Protein for Assessment of Kidney Function in Neonates.

INTRODUCTION: Compared to the conventional methods, serum beta-trace protein (BTP) has been shown to be more helpful for estimating glomerular filtration rate; however, its value is remained unclear in neonates. The present study aimed to investigate the range of serum BTP level in healthy term neonates and its value to estimate glomerular filtration rate. MATERIALS AND METHODS: This cross-sectional study was conducted on 50 healthy term neonates without underlying cardiovascular or kidney disorders who were admitted to Ali Asghar hospital in 2013. Serum BTP was measured using an automated nephelometric immunoassay. Glomerular filtration rate was assessed using the Schwartz equation based on serum creatinine level. RESULTS: The mean age of the neonates was 6.2 ± 3.6 days (range, 2 to 17 days), their mean gestational age was 38.02 ± 0.20 weeks, and their mean height was 49.8 ± 1.7 cm. The mean serum BTP level was 0.41 ± 0.11 mg/L (range, 0.19 mg/L to 0.92 mg/L). The mean serum creatinine level was 0.49 ± 0.16 mg/dL (range, 0.3 mg/dL to 1.0 mg/dL). The mean estimated GFR was 48.90 ± 15.88 mL/min. A positive correlation was observed between the reciprocal concentrations of BTP and GFR (r = 0.383, P = .006). Furthermore, the reciprocal concentrations of BTP was associated with the reciprocal concentrations of serum creatinine level (r = 0.365, P = .009). CONCLUSIONS: Measurement of serum BTP can be a reliable tool for detecting kidney function in neonates. Further studies are warranted to design a suitable formula for GFR estimation based on serum BTP in neonates.

Assessment of Renal Injury in Patients Undergoing Elective EVAR Using Urinary Neutrophil Gelatin-Associated Lipocalin, Interleukin 18, and Retinol-Binding Protein.

Acute kidney injury (AKI) is a recognized complication post-endovascular aneurysm repair (EVAR). Neutrophil gelatin-associated lipocalin (NGAL), interleukin 18 (IL-18), and retinol-binding protein are emerging urinary biomarkers that have shown promise in detecting subclinical and clinical renal impairment. In this study, we assessed changes in these urinary biomarkers as well as serum creatinine (SCr) in patients undergoing EVAR. Urine samples were collected prospectively at 5 time points for each recruited patient: pre-EVAR (baseline) and 6, 12, 24, and 48 hours after the procedure for serial assessment of urinary biomarkers. Serum creatinine was quantified preoperatively and at 24 and 48 hours postoperatively. Serial changes of urinary biomarkers and SCr were assessed. A significant increase in NGAL and IL-18 from baseline was observed ( P < .05), as early as 6 hours for NGAL. A significant rise in levels of NGAL and IL-18 precedes the significant rise in SCr. These findings highlight the potential of emerging urinary biomarkers in detecting early AKI following EVAR.

Evaluation of KIM-1 and NGAL as Early Indicators for Assessment of Gentamycin-Induced Nephrotoxicity In Vivo and In Vitro.

BACKGROUND/AIMS: The aminolycoside Gentamicin is a widely used antibiotic, applied in equine medicine. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity. Early detection of renal damage is critical in preclinical drug development. This study was aimed to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be early indicators in the assessment of Gentamycin-induced nephrotoxicity. METHODS: In our study, a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50 or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal toxicity during the progression of acute kidney injury (AKI). Additionally, biomarkers were assessed in human kidney proximal epithelial cells (HK-2) treated with Gentamicin for 2, 6, 12, 24, 36 or 48h in vitro. RESULTS: Repeated administration of Gentamicin to rats for 1, 3, or 7 days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. The expressions of the two biomarkers changed prior to renal tubule damage and increases in serum creatinine (SCr) and blood urea nitrogen (BUN) levels, suggesting their usefulness for predicting Gentamicin-induced acute kidney injury (AKI) in vivo. CONCLUSIONS: In contrast, no significant increase in the expression of the biomarker genes and proteins were evident in HK-2 cells after treated by Gentamycin for up to 48h, suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.

Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI).

BACKGROUND AND OBJECTIVES: Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children's Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age. RESULTS: At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid-binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls. CONCLUSIONS: Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.

Avaliação dos biomarcadores urinários no controle do tratamento de estenose de junção ureteropélvica em adulto / The role of urinary biomarkers in the assessment of ureteropelvic junction obstruction in adults

INTRODUÇÃO E OBJETIVO: A estenose de junção ureteropélvica (EJUP) é importante causa de obstrução do trato urinário e pode levar a deterioração progressiva da função renal. Há espaço para o aprimoramento de novos métodos diagnósticos capazes de discriminar hidronefrose e uropatia obstrutiva. Acredita-se que os biomarcadores urinários podem fornecer indícios de lesão renal precoce na obstrução urinária. Neste contexto, KIM-1 pode elevar-se na urina por lesão tubular proximal, NGAL por lesão no túbulo proximal, distal ou alça de Henle, CA19-9 por produção excessiva no túbulo obstruído e ?2-microglobulina (beta2M) por injúria ao glomérulo ou ao túbulo proximal. O objetivo do presente estudo foi avaliar as propriedades diagnósticas dos biomarcadores urinários citados em adultos com EJUP, sendo o primeiro estudo na literatura a avaliar tais moléculas nesta população. MÉTODOS: Foram estudados de modo prospectivo pacientes consecutivos acima de 18 anos com diagnóstico de EJUP submetidos a pieloplastia videolaparoscópica de dezembro de 2013 a fevereiro de 2015. Foram excluídos do estudo pacientes com EJUP bilateral, rim contralateral patológico, EJUP em rim único, antecedentes de tratamento cirúrgico para estenose de JUP ou taxa de filtração glomerular inferior a 60 ml/min/1,73m2. Cada paciente forneceu quatro amostras de urina para medição de biomarcadores, uma no pré-operatório e outras com 1, 3 e 6 meses de seguimento pós-operatório. O grupo controle foi constituído por voluntários saudáveis sem hidronefrose à ultrassonografia. RESULTADOS: Foram incluídos 47 pacientes com idade média de 38,6 ± 12,7 anos (intervalo 19 a 64 anos), sendo 17 (36,2%) do sexo masculino e 30 (62,8%) do sexo feminino. O grupo controle foi composto por 40 indivíduos semelhantes ao grupo com EJUP no que concerne idade (p = 0,95) e sexo (p = 0,82). KIM-1 foi o marcador com melhores propriedades diagnósticas, apresentando área sob a curva (AUC) de 0,79 (95% CI 0,70 a...

INTRODUCTION AND OBJECTIVE: Ureteropelvic junction obstruction (UPJO) is an important cause of urinary tract obstruction and can lead to progressive deterioration of renal function. Thus the development of novel non-invasive methods capable of discriminating obstruction and hydronephrosis may be useful. Elevation of urinary biomarkers may provide early evidence of kidney damage in urinary obstruction. In this scenario, urinary concentrations of KIM-1 may be elevated following proximal tubular injury, while NGAL may increase as result of injury to proximal or distal tubule as well as to loop of Henle, CA19-9 after overproduction in the obstructed tubule and ?2 microglobulin (beta2M) after injury to the glomerulus or the proximal tubule. The aim of this study was to evaluate the diagnostic properties of these urinary biomarkers in adults with UPJO. METHODS: We prospectively studied consecutive patients older than 18 years diagnosed with UPJO undergoing laparoscopic pyeloplasty from December 2013 to February 2015 in our institution. Exclusion criteria included patients with bilateral UPJO, unilateral UPJO with contralateral pathologic kidney, solitary kidney, history of previous surgical treatment for UPJO or glomerular filtration rate below 60 ml/min/1,73m2. Each patient provided four voided urine samples for biomarker measurement, one at preoperative consultation and the others at 1, 3 and 6 months of postoperative follow-up. Healthy individuals with no hydronephrosis on ultrasound evaluation constituted our control group. RESULTS: We included 47 patients with a mean age of 38.6 ± 12.7 years (range 19-64 years), from which 17 (36.2%) were males and 30 (62.8%) were females. The control group consisted of 40 subjects with no statistical difference to the study group regarding age (p = 0.95) and gender (p = 0.82). KIM-1 had an area under the curve (AUC) of 0.79 (95% CI 0.70 to 0.89) and was the biomarker with the...

Assessment of fractional excretion of urea for early diagnosis of cardiac surgery associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine, but it is not widely used in clinical practice. Fractional excretion of urea (FeU) has been referred to as a useful tool to discriminate between prerenal and established AKI. The aim of our study is to evaluate the sensitivity and specificity of FeU, in the early diagnosis of AKI in patients undergoing CS. METHODS: We performed a prospective study on adults undergoing CS. AKI was defined by AKIN criteria. Individuals suffering from CKD, were excluded. Sensitivity and specificity of FeU, fractional excretion of sodium (FeNa) and urine NGAL, measured at 1, 6 and 24 h following CS, were assessed. RESULTS: We included 66 patients (26% female) aging 68 ± 11 years. AKI prevalence was 24% and mortality was 3.28%. Patients with AKI had a significantly lower FeU compared to those without AKI (23.89 ± 0.67% vs. 34.22 ± 0.58%; p < 0.05) 6 h after CS, but not at the 1- and 24-h time points. NGAL was also statistically significant between both groups. FeU showed a 75% sensitivity and 79.5% specificity; the AUC was 0.786. ROC analysis of FeU and NGAL yielded similar values (p = NS). CONCLUSION: FeU is useful as an early biomarker to predict AKI after CS and it is comparable to the new biomarker NGAL.

Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery.

INTRODUCTION: Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level). MATERIALS AND METHODS: We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER). RESULTS: Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of $8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was $5959.35/QALY. CONCLUSIONS: Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery.

Effects of phosphodiesterase-5 inhibitor on ischemic kidney injury during nephron sparing surgery: quantitative assessment by NGAL and KIM-1.

PURPOSE: Interruption of renal blood flow is often necessary during nephron sparing surgery (NSS) and can induce renal injury. This study examines whether tadalafil, a phosphodiesterase-5 (PDE-5) inhibitor and well-known vasodilator, exerts nephroprotective effects in patients undergoing NSS. METHODS: This non-randomized study included 49 patients with enhancing solid renal mass. All patients were subjected to open NSS during which clamping the renal artery was performed. Twenty-two patients were pretreated with tadalafil 1 day prior NSS and 2 days following surgery. The other 27 patients underwent the same surgical procedure but did not receive tadalafil (controls). Urine samples were collected before surgery and following renal pedicle clamp removal. Urine levels of NGAL and KIM-1, two novel biomarkers for acute kidney injury (AKI), were determined. RESULTS: Clamping the renal artery induced kidney dysfunction as reflected by increases in urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted for 72 and 24 h, respectively. Pretreatment with tadalafil reduced the absolute urinary excretion of KIM-1, but not of NGAL. Although the incidence of AKI was comparable between tadalafil-treated and untreated NSS subjects, the elevation in serum creatinine (SCr) was significantly attenuated in tadalafil-treated group as compared with NSS controls. CONCLUSIONS: Tadalafil exerts nephroprotective effects in AKI following NSS, as was evident by reduced urinary excretion of KIM-1 and attenuation of SCr elevation. Carefully controlled large clinical studies are needed before defining the role of PDE-5 inhibition therapy in these patients.

Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury.

PURPOSE: To assess urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein 7 ([TIMP-2]·[IGFBP7]), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney injury predictors (AKI) exploring the association of nonrenal factors with elevated biomarker levels. METHODS: We studied 94 patients with urine collected within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Predictive performance was assessed by the area under the receiver operating characteristics (ROC) curve. Associations between biomarkers and clinical factors were assessed by multivariate linear regression. RESULTS: Overall, 19 patients (20%) developed AKI within 48 hours. [TIMP-2]·[IGFBP7], NGAL, or cystatin-C admission levels did not differ between patients without AKI and patients developing AKI. [TIMP-2]·[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34-0.51). Diabetes was independently associated with higher [TIMP-2]·[IGFBP7] levels (P = 0.02) but AKI was not (P = 0.24). Sepsis was independently associated with higher NGAL (P < 0.001) and cystatin-C (P = 0.003) levels. CONCLUSIONS: Urinary [TIMP-2]·[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in general ICU patients since urine levels of these biomarkers are affected by factors other than AKI and their performance can be poor.

Comparative assessment of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C as early biomarkers for early detection of renal failure in patients with hypertension.

BACKGROUND: Hypertension is one the most common causes of chronic kidney disease (CKD). One of the major concerns in hypertensive patients is early detection of renal disorders. In the past, serum creatinine (Scr) concentration was used as a marker of kidney function, but it proffers a late reflection of reduced glomerular filtration rate. Cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) have been recently proven to be useful for quantification of CKD. Therefore, we compared the diagnostic value of NGAL with cystatin C and creatinine to evaluate kidney function in hypertensive patients. METHODS: In this study, 42 hypertensive patients and 30 healthy volunteers were recruited. Serum cystatin C (Scys C) and plasma NGAL were measured using ELISA method. Creatinine, urea, hemoglobin, fibrinogen, and C-reactive protein were measured according to the routine methods. Estimated glomerular filtration rate (eGFR) was considered as the gold standard method (cut-off value of < 78 ml/min/1.73 m². RESULTS: In the patient group, plasma NGAL, cystatin C, and creatinine were all significantly correlated with eGFR, and plasma NGAL correlated best with eGFR. Receiver-operating characteristics analysis indicated that plasma NGAL was a better indicator than creatinine and cystatin C for predicting a GFR < 78 ml/min/1.73 m2. The sensitivity and specificity for NGAL were 96% and 100%, for cystatin C were 92% and 60% and for creatinine were 76% and 47%, respectively. CONCLUSION: Plasma NGAL demonstrated a higher diagnostic value to detect kidney impairment in the early stages of CKD as compared to Scys C and Scr in hypertensive patients.

Towards a biomarker panel for the assessment of AKI in children receiving intensive care.

BACKGROUND: Critically ill children and neonates are at high risk of developing acute kidney injury (AKI). AKI is associated with short- and long-term renal impairment and increased mortality. Current methods of diagnosing AKI rely on measurements of serum creatinine, which is a late and insensitive marker. Few studies to date have assessed AKI biomarkers in a heterogeneous patient cohort. METHODS: We conducted a prospective feasibility study in a paediatric intensive care setting over a 6-month period to describe the relationship between AKI (defined according to pRIFLE criteria) and new AKI biomarkers. RESULTS: In total, 49 patients between the ages of 16 days and 15 years were recruited for measurement of plasma cystatin C (Cys-C) and neutrophil gelatinase-associated lipocalin (pNGAL) concentrations, as well as for urinary kidney injury molecule-1 (KIM-1) and urinary NGAL (uNGAL) concentrations. Almost one-half (49 %) of the patient cohort experienced an AKI episode, and Cys-C and pNGAL were the strongest candidates for the detection of AKI. Our data suggest that the widely used estimated baseline creatinine clearance value of 120 mL/min/1.73 m(2) underestimates actual baseline function in patients admitted to paediatric intensive care units. CONCLUSIONS: This investigation demonstrates the feasibility of new AKI biomarker testing in a mixed patient cohort and provides novel biomarker profiling for further evaluation.

Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology.

BACKGROUND: Ischemic acute kidney injury is a common occurrence in the perioperative period and in critical patients admitted to intensive care units. The reestablishment of blood supply may worsen injury through the ischemia-reperfusion (I/R) mechanism. We investigated the effect of dexmedetomidine on the kidneys of rats subjected to an experimental I/R model. METHODS: 34 rats anesthetized with isoflurane was undergone right nephrectomy and randomly assigned to four groups: Control C (saline solution); Dexmedetomidine D (dexmedetomidine); Sham S (saline solution); Sham with Dexmedetomidine SD (dexmedetomidine). The serum levels of neutrophil gelatinase-associated lipocalin (NGAL) were measured at time-points T1 (following stabilization), T2 (ischemia), T3 (reperfusion), T4 (12 h after of I/R). The kidneys were subjected to histological examination. RESULTS: The NGAL levels were significantly higher at T4 compared with T1. Upon histological examination, the left kidneys in groups C and D exhibited a similar extent of cell injury. CONCLUSION: The levels of NGAL did not indicate either protection against or worsening of kidney injury. Histological examination for acute tubular necrosis showed that dexmedetomidine did not protect the kidneys from I/R.

Assessment of neutrophil gelatinase-associated lipocalin in the brain-dead organ donor to predict immediate graft function in kidney recipients: a prospective, multicenter study.

BACKGROUND: Delayed graft function is a major determinant of long-term renal allograft survival. Despite considerable efforts to improve donor selection and matching, incidence of delayed graft function remains close to 25%. As neutrophil gelatinase-associated lipocalin (NGAL) has been shown to predict acute renal failure, the authors tested the hypothesis that NGAL measurement in brain-dead donors predicts delayed graft function in kidney recipients. METHODS: In a prospective, multicenter, observational study, serum NGAL was measured in donors at the time of transfer to operating room. The primary endpoint was the delayed graft function, defined as the need for renal replacement therapy during the first week posttransplantation. RESULTS: Among 159 included brain-dead donors, 146 were analyzable leading to 243 renal transplantations. Of these, 56 (23%) needed renal replacement therapy. Donors' NGAL values were similar in case of both delayed and normal graft function in recipients. The area under the receiver-operating curve for NGAL to predict the need for renal replacement therapy before day 8 was 0.50 (95% CI, 0.42 to 0.59). The area under curve for NGAL to predict failure to return to a normal graft function at day 8 was 0.51 (95% CI, 0.44 to 0.59). Using multivariate analysis, NGAL was not associated to the need for renal replacement therapy (odds ratio, 0.99; 95% CI, 0.98 to1.00) or failure to return to a normal graft function at day 8 (odds ratio, 1.00; 95% CI, 0.99 to 1.00). CONCLUSION: NGAL measurement in brain-dead donors at the time of recovery failed to predict delayed or normal graft function in kidney recipients.