Early Diagnostic Value of Urinary NGAL in Acute Kidney Injury in Septic Patients.

Background: The aim of this study was to evaluate the predictive value of urinary neutrophil gelatinase-associated lipid (uNGAL) for the prediction of sepsis-associated acute kidney injury (SA-AKI). Methods: From September to December 2012, 110 patients were prospectively enrolled from the intensive care units (ICUs) of 3 general hospitals. After being admitted to the ICU, the patients were continuously observed for 72 hours. According to the Kidney Disease Improving Global Outcomes (KDIGO) criteria for the diagnosis of acute kidney injury (AKI), the patients were divided into the AKI group (33 patients) and non-AKI group (77 patients). Per the sepsis diagnostic criteria, the patients were classified as septic (79 patients) and non-septic (31 patients). Serum creatinine and uNGAL of the patients were analyzed daily. The difference in uNGAL in septic and non-septic patients, patients with and without AKI, and septic patients with with and without AKI were compared. In addition, the difference in serum creatinine and uNGAL in patients with and without AKI were recorded and compared, and the sensitivity and specificity of uNGAL and sCr for the diagnosis of AKI in the ICU patients were evaluated using the receiver operating characteristic (ROC) curve. Results: uNGAL levels were all significantly different in septic and non-septic patients (P = .001, P = .028, P = .010, respectively), patients with and without AKI (P = .001, P = .042, P = .001, respectively), septic patients with AKI and septic patients without AKI (P = .003, P = .012, P = .001, respectively) at 24, 48 and 72 hours after being admitted to the ICU, while the difference in sCr was not significant (P = .169) after 24 hours. The area under the ROC curve of uNGAL and sCr in patients admitted to the ICU at 24 hours were 0.828 (95% CI, 0.742 to 0.914) and 0.583 (95% CI, 0.471 to 0.695), respectively. The cutoff value of uNGAL was 170 ng/mL in patients admitted to the ICU at 24 hours, and the sensitivity and specificity were 0.778 and 0.784, respectively. The sensitivity of uNGAL was superior sCr. Conclusion: uNGAL has relatively high sensitivity and specificity in predicting the occurrence of AKI in septic patients, which is superior to sCr and has certain clinical early diagnostic value. uNGAL could be used as an indicator for early diagnosis of AKI in septic patients in the ICU.

Evaluation of kidney dysfunction in childhood cancer survivors.

BACKGROUND: The major increase in the survival rate among children with cancer is due to improvement in the diagnosis and treatment. Despite this increase, childhood cancer survivors (CCS) are at high risk of developing late complications such as nephrotoxicity due to chemotherapy. So, we aimed to detect early subclinical kidney dysfunction among CCS. METHODS: This cross-sectional study was implemented on 52 survivors of childhood cancer recruited from Pediatric Oncology Unit, Menoufia University. Laboratory evaluations for each participant, including complete blood count, serum urea, creatinine, urinary protein, urinary calcium, uric acid, and serum cystatin C and urinary Neutrophil Gelatinase Associated Lipocalin (UrNGAL) by ELISA were obtained. RESULTS: Estimated GFR was decreased in 23.1% of cases, with elevated serum cystatin C, UrNGAL and UrNGAL/Cr. There was a significant increase of Uprotein/Cr, UCa/Cr, UACR (p = 0.02), UrNGAL and UrNGAL/Cr (P < 0.001) in patients with tubular dysfunction compared without tubular dysfunction. There was a significant difference between two groups regarding cisplatin (P = 0.03) and high-dose methotrexate chemotherapy (p = 0.04). The AUCs for detecting kidney tubular dysfunction by UrNGAL and UrNGAL/Cr were 0.807 and 0.747. CONCLUSION: A significant tubular dysfunction among childhood cancer survivors receiving chemotherapy as cisplatin and high-dose methotrexate. IMPACT: Detection of kidney dysfunction mainly tubular in childhood cancer survivors after finishing chemotherapy. Urinary NGAL is a good predictor for detection of tubular dysfunction in childhood cancer survivors after finishing chemotherapy.

Biomarkers for febrile urinary tract infection in children.

BACKGROUND: The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. METHODS: This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. RESULTS: We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. CONCLUSIONS: NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury.

BACKGROUND: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N-acetyl-ß-d-glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation-Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. METHODS: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C. RESULTS: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300-815 mg), which induced a urine output of 8425 mL (interquartile range, 6341-10 528 mL) over the 72-hour intervention period. Levels of N-acetyl-ß-d-glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P>0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (-8.7 ng/mg; interquartile range, -169 to 35 ng/mg; P<0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin (P=0.21), N-acetyl-ß-d-glucosaminidase (P=0.46), or kidney injury molecule 1 (P=0.22). Increases in neutrophil gelatinase-associated lipocalin, N-acetyl-ß-d-glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69-0.91; P=0.001). CONCLUSIONS: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy.

BACKGROUND: Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury. METHODS: Twenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates. RESULTS: Urinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3µg/mmol versus 533.6µg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups. CONCLUSIONS: Ascorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.

Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility on uric acid metabolism and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in rats with hyperuricemia.

OBJECTIVE: To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility (PR) on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in rats with hyperuricemia. METHODS: Seventy male Sprague Dawley (SD) rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses (3.5, 7, 14 g/kg). Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid (SUA), blood urea nitrogen (BUN) and creatinine (Cr) were determined. In addition, the contents of NGAL and KIM-1 in urine and the mRNA and protein expressions of xanthine oxidase (XOD) in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin (HE) stain method. RESULTS: Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD mRNA and protein in the hyperuricemia rats were increased signifificantly (P<0.01). PR signifificantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the mRNA and protein expressions of hepatic XOD (P<0.05 or P<0.01). In addition, the pathological changes of kidney were signifificantly suppressed by oral administration of PR. CONCLUSIONS: PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.