Urinary Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

Urinary Soluble Chemokine (C-X-C Motif) Ligand 16 (CXCL16) and Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) as Biomarkers of Activity in Children and Adolescents with Lupus Nephritis

Objectives: One of the challenges of treating patients with lupus nephritis (LN) is to assess disease activity and predict its outcome. Since renal biopsy cannot be performed routinely, early biomarkers are needed. The aim of this study was to measure urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) and urinary soluble chemokine (C-X-C motif) Ligand 16 (CXCL16) levels in children and adolescents with Systemic lupus erythematosus (SLE) and investigate whether they are elevated in active LN.\r\nMethods: The study was conducted on 80 patients diagnosed as SLE by Systemic Lupus International Collaborating Clinics (SLICC) criteria and 60 apparently healthy subjects as controls. Global and renal disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and r SLEDAI respectively. Urinary NGAL and Urinary CXCL16 were measured for all subjects by ELISA. Renal biopsy was done for all cases at initial diagnosis and was graded using ISN/RPS classification.\r\nResults: Urinary NGAL and CXCL16 were higher in patients than in the controls. Their levels were higher in patients with LN than those without LN. Urinary NGAL had higher sensitivity and specificity than urinary CXCL16 as early predictor of LN. There were significant positive correlations between urinary NGAL levels and 24 hour urinary proteins and SLEDAI and there were also significant positive correlations between urinary CXCL16 levels and 24 hour urinary proteins and SLEDAI.\r\nConclusions: uNGAL and CXCL16 were reliable indicators of the activity of LN pointing to the underlying renal pathology.

Urinary RBP and NGAL Levels are Associated with Nephropathy in Patients with Type 2 Diabetes

Background/Aims: The diagnosis of type 2 diabetic nephropathy (T2DN) patients is important to prevent the long-term damaging effects of kidney loss in patients with diabetes and is decisive for patient outcomes. The aim of this study was to explore urine retinol binding protein (RBP) and neutrophil gelatinase-associated lipocalin (NGAL) in T2DN patients with and without albuminuria. Methods: A total of 293 T2DN patients were divided into three groups according to their urine albumin/urine creatinine ratio (UACR): normoalbuminuria group (UACR<30 mg/g, n=100), microalbuminuria group (UACR 30–300 mg/g, n=100) and macroalbuminuria group (UACR>300 mg/g, n=93); 50 non-diabetic subjects were recruited as the control group. The levels of urine RBP, NGAL, TNF-α and IL-18 in T2DN patients and non-diabetic subjects were measured using ELISA assays. Results: We first analyzed the clinical characteristics of the control and T2DN groups and found that urine NGAL, RBP, TNF-α and IL-18 levels were significantly increased and significantly correlated with the degree of albuminuria. In addition, univariate linear regression analysis showed that urine RBP was associated with UACR, BMI, Scr, BUN, TG, disease duration, SBP, NGAL, TNF-α and IL-18 levels, and urine NGAL was positively correlated with UACR, Scr, BUN, RBP, TNF-α and IL-18 levels. Conclusion: The results indicate that urine levels of NGAL and RBP may be independently associated with albuminuria in T2DN and may serve as novel biomarkers for the identification of T2DN.

Effects of atorvastatin on biomarkers of acute kidney injury in amikacin recipients: A pilot, randomized, placebo-controlled, clinical trial.

Background:The most common clinical indication of aminoglycosides (AG) is the treatment of serious Gram-negative infections. The aim of this study was to evaluate plausible effects of atorvastatin on the biomarkers of acute kidney injury (AKI) in patients receiving amikacin.Materials and Methods:In this double-blinded randomized clinical trial, fifty patients (25 in each group) receiving amikacin (15 mg/kg/day) were randomly assigned to either atorvastatin (40 mg/day) or placebo (40 mg/day) groups for 7 days. Blood urea nitrogen (BUN), serum creatinine (SCr), and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels were measured at days 0, 1, and 7 of amikacin treatment.Results:During the study period, 4 (8%) patients including two patients in each atorvastatin and placebo group experienced AKI. Urine NGAL/urine Cr did not change significantly between and within placebo and atorvastatin groups during the study period. Similarly, the mean changes in SCr, BUN, and urine NGAL/urine Cr values did not differ significantly between and within patients with and without AKI.Conclusion:Our data suggested that the changing pattern of urine NGAL/urine Cr ratio did not differ significantly between the atorvastatin and placebo groups during the early phase of amikacin treatment.

Neutrophil Gelatinase-Associated Lipocalin Levels During Pneumoperitoneum.

Background and Objectives:A temporary deterioration in renal function during pneumoperitoneum has been reported, but the extent is not known. A new marker for the early detection of renal injury, neutrophil gelatinase-associated lipocalin (NGAL), has been shown to increase in various conditions that affect renal function. This study was conducted to explore detrimental effects of pneumoperitoneum in laparoscopic surgery on renal function by studying levels of urinary NGAL (uNGAL).Methods:Thirty-two women scheduled to undergo laparoscopic surgery in a gynecology clinic were recruited. NGAL was measured in urine collected at the beginning (0 h) and at 2 and 24 hours after the initiation of surgery. Hemodynamic parameters were analyzed immediately after intubation and before desufflation.Results:Levels of uNGAL increased from 5.45 ng/mL at 0 hours to 6.35 ng/mL at 2 hours and to 6.05 ng/mL at 24 h; however, there was no significant change in uNGAL levels at the collection time points. Intraoperative oliguria was observed in all cases, and the severity increased with the duration of surgery. uNGAL levels did not correlate with the duration of surgery or pneumoperitoneum.Conclusion:In patients with normal renal functions, pneumoperitoneum results in transient oliguria without any early renal damage, as indicated by nonsignificant changes in uNGAL levels.

The value of urinary neutrophil gelatinase-associated lipocalin for early diagnosis of contrast-induced nephropathy

Objective: To explore the value of urinary neutrophil gelatinase-associated lipocalin (NGAL) for early diagnosis of contrast-induced nephropathy (CIN) in patients who underwent percutaneous coronary angiography (CAG) or percutaneous coronary intervention (PCI). Methods: From May 2015 to January 2016, 506 consecutive patients who underwent CAG or PCI in our hospital were enrolled in this prospective study. Patients were divided into CIN group (n=47) and non-CIN group (n=459). Clinical and interventional data were compared between the two groups. Spearman ranking correlation coefficient was used to define the relation between NGAL and CIN, and multivariable logistic regression analysis was performed to identif independent predictors of CIN. Receiver-operator characteristic (ROC) curve was generated, and area under the curve (AUC) was calculated and sensitivity and specificity for CIN diagnosis were analyzed. Results: (1) Basic clinical and interventional data including age, incidence of diabetes, hypertension and chronic heart failure, level of systolic blood pressure, serum creatine before procedure, use of isotonic contrast agent, contrast volume, Mehran score, operation time, treatment number of coronary artery, hydration and medication were all similar between two groups (all P>0.05). (2) Urinary NAGL level at 24 and 48 h after procedure, serum creatinine (Scr) level at 48 h after procedure, and ΔNGAL24-0 h were significantly higher in CIN group than in non-CIN group (all P<0.01), but the differences of urinary NGAL level before procedure, Scr level 24 h after procedure, and ΔNGAL48-24 h were similar between two groups (all P>0.05). (3)The positive correlation was found by Spearman ranking correlation between ΔNGAL24-0 h and CIN (r=0.478, P<0.001). (4) Multivariable logistic regression analysis showed that estimated glomerular filtration rate(OR=1.020, 95%CI 1.005-1.035, P=0.007) and ΔNGAL24-0 h (OR=1.020, 95%CI 1.014-1.027, P<0.001) were the independent predictors of CIN.(5) ROC curve showed that the AUC of NGAL with the cutoff value 4.65 was 0.899(0.854, 0.944)for diagnosis of CIN (sensitivity 93.6%, and specificity 0.944). Conclusion: The rise of urinary NGAL level at 24 and 48 hours after CAG or PCI is suggestive of CIN and could be used as a reliable parameter for the early diagnose of CIN.

The protective effect of human atrial natriuretic peptide on renal damage during cardiac surgery

PurposeAcute kidney injury (AKI) is one of the critical complications after cardiac surgery. In the kidney, angiotensin II (Ang II) is formed by independent mechanisms, and activity of the intrarenal renin–angiotensin–aldosterone (RAAS) system contributes to the progression of kidney damage. Although atrial natriuretic peptide (ANP) exerts protective effects against renal injury by inhibiting the RAAS, the mechanisms of this effect have not been completely clarified. We investigated how human ANP (hANP) could prevent renal damage induced by cardiopulmonary bypass.MethodsForty-eight patients undergoing cardiac surgery were divided into two groups, with and without hANP infusion. Urinary angiotensinogen, neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) were measured during and after surgery in both groups. Plasma renin activity, Ang II, aldosterone and serum creatinine were also measured.ResultsUrinary angiotensinogen levels in the hANP group were significantly lower than in the non-hANP group after cardiopulmonary bypass surgery, at the end of surgery and 3 h after surgery. At 3 h after surgery, urinary NGAL levels in the hANP and non-hANP groups were 371.1 ± 413.6 and 761.4 ± 437.8 μg/gCr, respectively (p < 0.01). Urinary L-FABP levels at the end of surgery in the hANP and non-hANP groups were 238.8 ± 107.4 and 573.9 ± 370.1 μg/gCr, respectively (p < 0.01). Moreover, hANP seemed to significantly reduce the incidence of postoperative AKI.ConclusionshANP demonstrated renal protective effects during cardiac surgery, and could possibly reduce the incidence of AKI after ischemia–reperfusion surgery. Moreover, this protective effect of hANP is likely induced by inhibition of the intrarenal RAAS.

Abstract 13460: Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin for Adverse Events in Patients With Acute Decompensated Heart Failure

Background: urinary neutrophil gelatinase-associated lipocalin (U-NGAL) has been reported as an earlier predictor of acute kidney injury (AKI) and a prognostic factor of adverse events in patients with chronic heart failure, but in acute decompensated heart failure (ADHF) patients the significance is poorly understood. Methods: We have studied consecutive 436 patients with ADHF admitted to our department from 2011 through 2014. Among these patients, 260 patients measured U-NGAL using 24-hour urine samples collected on day 1 were studied. The primary endpoints were all-cause death, cardiovascular (CV) death and HF admission. Results: We divided into two groups on the basis of the median U-NGAL levels (32.5 μg/gCr). The high U-NGAL group had significantly higher the occurrence of AKI during hospitalization than the low U-NGAL group (p=0.0012). Kaplan-Meier analysis revealed that high U-NAGL group had worse prognosis than low U-NGAL group in all-cause death (Hazard ratio (HR): 2.07; 95% confidence interval (CI): 1.38-3.12, p=0.0004), CV death (HR: 2.29; 95% CI: 1.28-4.24, p=0.0052), and HF admission (HR: 1.77; 95% CI: 1.13-2.77, p=0.0119) (Figure 1). Multivariate analysis revealed that high U-NGAL predicted all-cause death and HF admission (HR: 1.77; 95% CI: 1.17-2.72, p=0.0073; and HR: 1.69; 95% CI: 1.05-2.72, p=0.0293, respectively). In subgroup analyses, high U-NGAL predicted all-cause death in reduced LVEF (HFrEF, &lt;50%) patients, but not in preserved LVEF (HFpEF, ≥50%) patients, with the significant interaction (p=0.0005) (Figure 2). Conclusions: In ADHF patients, elevated level of U-NGAL was related to development of clinical AKI and associated with poor prognosis.

The Role of Urinary Lipocalin in Prognostication of Hospital Complications in Patients With Ischemic Heart Disease After Coronary Artery Bypass Grafting

To assess significance of urinary neutrophil gelatinase-associated lipocalin (NGAL) for predicting hospital complications in subjects with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG). The study included 720 subjects who underwent CABG between 03/2011 and 04/2012. Blood serum creatinine level, glomerular filtration rate (GFR) (MDRD formula) and NGAL concentration were measured before and on day 7 after CABG. The following unfavorable outcomes of operative intervention: myocardial infarction (MI), stroke or transient ischemic attack, acute or progression of chronic renal disease, remediastinotomy were registered during in-hospital period. Additive EuroSCORE was calculated for all patients. There were no significant differences in serum creatinine level and GFR both before and on day 7 after CABG between groups of patients with different risk assessed by EuroSCORE, and with complicated and uncomplicated postoperative course. Urine NGAL level before and on day 7 after CABG was significantly higher in high and medium compared with low EuroSCORE risk groups. Preoperative NGAL urine level was significantly higher in patients with than in those without MI or stroke after CABG. NGAL urine level was also higher in patients with development of acute renal failure (ARF) compared with those without ARF. Both pre- and postoperative NGAL urine levels were higher in patients with unfavorable outcome while there were no significant differences in serum creatinine levels and CRF between patients with favorable and unfavorable outcomes. Preoperative measurement of urinary NGAL - a preclinical marker of acute kidney injury - allowed to predict more accurately the hospital risk of development of adverse cardiovascular and renal complications of CABG.

Neutrophil gelatinase-associated lipocalin (NGAL) value changes before and after shock wave lithotripsy.

Our aim was to determine short and medium-term changes of neutrophil gelatinase-associated lipocalin (NGAL) in the urine of patients undergoing shock wave lithotripsy (SWL). In patients with kidney stones, serum urea and creatinine (Cr), urine Cr and NGAL levels were determined immediately before and at 3, 24h and 30days after SWL. Urine NGAL concentrations were normalized to urinary Cr ruling out the confounding effect of variable hydration states. Thirty-five patients with a single renal stone were enrolled. Inclusion criteria were: first SWL treatment for each patient, single radiopaque renal stone <20mm; normal renal function. Exclusion criteria were: body mass index (BMI)>30kg/m2, recent episodes of renal colic (less than 3months), the presence of radiolucent stones, renal impairment, upper urinary tract obstruction or malignancy, acute pyelonephritis, patients who consumed potentially nephrotoxic drugs within 4weeks before the evaluation. Geometric means of urinary NGAL/Cr ratio measured 3h after SWL were significantly higher than baseline values (difference 7.56ng/mg, 95% confidence interval 1.61, 13.51; p value=0.013). No changes were found for urinary NGAL/Cr measured at 24h (p value=0.92) and at 30days (p value=0.13) after SWL compared with baseline values. Urinary NGAL levels increase soon after SWL (3h) and quickly return to and maintain basal levels (1 and 30days). Further studies are necessary to understand the hypothetical role of NGAL as a guide to the degree of tissue injury after SWL.

Chronic recurrent dehydration associated with periodic water intake exacerbates hypertension and promotes renal damage in male spontaneously hypertensive rats.

Epidemiological evidence links recurrent dehydration associated with periodic water intake with chronic kidney disease (CKD). However, minimal attention has been paid to the long-term impact of periodic water intake on the progression of CKD and underlying mechanisms involved. Therefore we investigated the chronic effects of recurrent dehydration associated with periodic water restriction on arterial pressure and kidney function and morphology in male spontaneously hypertensive rats (SHR). Arterial pressure increased and glomerular filtration rate decreased in water-restricted SHR. This was observed in association with cyclic changes in urine osmolarity, indicative of recurrent dehydration. Additionally, water-restricted SHR demonstrated greater renal fibrosis and an imbalance in favour of pro-inflammatory cytokine-producing renal T cells compared to their control counterparts. Furthermore, urinary NGAL levels were greater in water-restricted than control SHR. Taken together, our results provide significant evidence that recurrent dehydration associated with chronic periodic drinking hastens the progression of CKD and hypertension, and suggest a potential role for repetitive bouts of acute renal injury driving renal inflammatory processes in this setting. Further studies are required to elucidate the specific pathways that drive the progression of recurrent dehydration-induced kidney disease.

Elevated Urinary biomarkers KIM-1 and NGAL may predict occurrence of Chronic Interstitial Nephritis (CINAC) in rural Sri Lanka

Chronic Interstitial Nephrities (CINAC) that cannot be attributed to known etiologies has encountered in rural Sri Lanka. CINAC is a tubular disease, urine albumin or albumin–creatinine ratio (ACR) is still being used as the screening tool. However they are incapable of assessing early stages of CINAC due to lack of sensitivity and specificity. In present study, we report the use of non-invasive, rapid and sensitive marker of tubule-epithelial cell damage (KIM-1 &amp; NGAL) for early CINAC diagnosis among sugarcane farmers in UP, Sri Lanka. Urine samples were collected from non-endemic controls living in wet zone (Matara-M) and in two locations representing sugarcane farmers ( Rahathangama (R1-S, R2-S) and Warunagama (W-S). Urinary KIM-1 and NGAL levels were measured using specific KIM-1 (Cusabio, P.R. China) and NGAL (Ray Biotech, USA) Enzyme Linked Immuno Sorbent Assay kits. Urine Creatinine was measured using Jaffe rate-blanked creatinine assay and final KIM-1 and NGAL were adjusted to UC. Urinary KIM-1 (μg/g Cr) and NGAL (ng/mg Cr) concentrations in M group were (2.885 ± 0.524, Mean ± SEM) and (0.568 ± 0.108) respectively. Mean KIM-1 in R1-S (12.49; 0 – 34.91 range) and R2-S (10.53; 0 – 61.66) were 4 times higher than M. NGAL concentrations in R1-S (1.93) and R2-S (1.06) were also significantly different from the M control group (p&lt;0.05). In W-S, creatinine adjusted urinary KIM-1 was 5.45 μg/g Cr and significantly lower than the R1-S and R2-S. However significantly higher urinary NGAL was reported in W-S (1.94 ng/mg Cr) with compared to control group (M). This study revealed that both urinary KIM-1 and NGAL concentrations were higher in sugarcane farmers with compared to the control group indicating that urinary KIM-1 and NGAL concentrations may be used as early predictive biomarkers for CINAC cases in rural Sri Lanka

URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AND CREATININE SERUM BPH PATIENTS WITH ACUTE URINE RETENTION TO DETECT KIDNEY FUNCTION DISORDERS

Objective: The main objective of this study was to determine renal function in patients with Benign Prostate Hyperplasia (BPH) in acute urinary retention period and two weeks after catheter insertion using creatinine serum and urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) biomarker parameters.Materials &amp; Method:This is an observational co-hort study conducted in patients with BPH with acute urinary retention who came to Soetomo General Hospital, Surabaya. All the patients underwent laboratory investigation that were urinary NGAL and creatinine serum, marker of renal function.Result: The mean creatinine serum of 31 samples when retention phase was 1.6 ± 0.9 mg/dL and it decreased after 2 weeks of urinary catheter insertion (1.46 ± 0.89 mg/dL). Mean urinary NGAL level when retention phase was 308.1 ± 244.8 ng/dL, and after 2 weeks after urinary catheter insertion it decreased to 158.5 ± 123.3 ng/dL. There was significant decreasing creatinine serum and urinary NGAL levels in patients with BPH and acute urinary retention in the retention phase 2 weeks after urinary catheter insertion, with p value &lt; 0.006 and &lt; 0.0001, respectively. There was no significant correlation between the duration of retention and urinary retention volume (p&gt;0.05).Conclusion: There was a significant decreasing creatinine serum and urinary NGAL levels in patients with BPH and acute urinary retention in retention phase and two weeks after urinary catheter insertion. There was no significant correlation between the urinary NGAL and creatinine serum and the duration of retention and urinary retention volume.

Evaluation of urinary KIM-1, NGAL, and IL-18 levels in determining early renal injury in pediatric cases with hypercalciuria and/or renal calculi.

One has to measure urinary enzymes and proteins to determine renal dysfunction and tubular injury in earlier stage during the course of disease. The aim of this study was to investigate the role of urinary NGAL (neutrophil gelatinase-associated lipocalin), IL-18 (Interleukin 18), and KIM-1 (kidney injury molecule-1) levels in determining early renal injury in pediatric patients with hypercalciuria (HC) and/or nephrolithiasis (NL) and to compare the levels of these markers between the sick and healthy subjects. Urinary NGAL, KIM- 1, and IL- 18 levels were measured in 40 pediatric patients diagnosed with NL, 23 patients with HC, and 20 healthy controls. A significant difference was found between patient groups (NL and HC) and healthy children with respect to urinary NGAL/cr ratio (p < 0.001). There were no significant differences between patient and control groups with respect to urinary IL18/cr and KIM1/cr ratios. We found that urinary NGAL is a useful marker for determining renal tubular damage in NL and HC. To our knowledge, this is the first study to report significantly increased urinary NGAL levels in NL and HC.

Predictive ability of urinary biomarkers for outcome in children with acute kidney injury.

Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay. Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls (p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL (p = 0.008) and NAG (p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580-0.920], followed by NAG at 0.724 (CI 0.541-0.907), with sensitivity and specificity of 75% each; and IL-18 (AUC 0.688, CI 0.511-0.864), with sensitivity 62.5% and specificity 70.8%, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay. Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay.

Cystatin C and NGAL as Biomarkers for Early Detection of Acute Kidney Injury in Geriatrics

Acute kidney injury (AKI) is associated with cardiovascular mortality and morbidity especially in high-risk patients undergoing cardiac surgery. It ranges from 7.7% to 28.1% in different studies. The aim of this study was to compare cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) with Creatinine as an early marker for acute kidney injury in geriatrics. From 2013 through 2015, 307 consecutive high-risk elderly patients older than 70 years undergoing emergency coronary artery bypass grafting using extracorporeal circulation were studied. All patients underwent diagnostic coronary angiography and the surgical procedure within 1 week in single hospital stay and were randomized according to timing of interval between coronary angiographyand cardiac procedure as follows: group I, less than 2 days; group II, between 2 and 4 days; and group III, higher than 4 days. Renal function was analyzed by serum cystatin C, NGAL, and creatinine. Blood samples were obtained from each patient at five time points: basal value before operation, in the four hours after operation, and on the first, third, and fifth postoperative days. Glomerular filtration rate (GFR) was calculated by Cockcroft-Gault (CG). A total of 56 patients developed postoperative acute kidney failure according to the risk, injury, and failure; and loss; and end-stage kidney disease classification. Perioperative fluid requirements, urine output, and vasopressor need during and after cardiopulmonary bypass were similar. 30-day mortality in groups was higher in group I than group II and group III (P = 0.025). AKI was least prominent in group III compared to group I and group II (P = 0.001) and expectedly, postoperative dialysis requirement was least common in group III (15, 16.66%). Patients in group III had the most favorable clinical outcome with regards to the length of ICU and hospital stay. Overall serum creatinine, cystatin C, and urine NGAL levels changed significantly throughout the entire length of following-up period in group I and group II, but not in group III. Changes in serum levels of cystatin, creatinine, and creatinine clearance were prominent in later than 24 hours. Urinary NGAL was the first variable to rise in the immediate postoperative period. Cystatin GFR was a more rapid marker than serum creatinine GFR to show acute kidney injury in three groups was a significant marker.

Predicting Severity of Acute Kidney Injury in Term Neonates with Perinatal Asphyxia Using Urinary Neutrophil Gelatinase Associated Lipocalin.

To evaluate the utility of urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for predicting Acute Kidney Injury (AKI) and its severity among neonates with perinatal asphyxia. This descriptive study included 120 term neonates with perinatal asphyxia. Renal parameters of neonates were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria. Urinary NGAL was estimated and correlated with severity of AKI. Among the 120 neonates with perinatal asphyxia, 55(46%) had AKI. The median urinary NGAL level was 165ng/ml (88.8-245.8) in neonates with AKI compared to 58.97(42.8-74.7) in those without AKI. The median NGAL was 134.45(112.2-162.5), 301.2(255.5-361.2), 416.2(412.2-465.5) in AKI stages 1, 2 and 3 respectively. An NGAL cut off value of 86.82ng/ml had 87% sensitivity and 87.7% specificity in predicting AKI. Urinary NGAL is a useful biomarker for predicting AKI and its severity among neonates with perinatal asphyxia.

Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study.

BackgroundAcute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease.In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis.MethodsUrine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls.ResultsFrom the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72–0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1).ConclusionsThis study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1344-z) contains supplementary material, which is available to authorized users.

Intra-abdominal Hypertension and Postoperative Kidney Dysfunction in Cardiac Surgery Patients.

To determine the incidence of intra-abdominal hypertension (IAH) in adult cardiac surgery patients and its association with postoperative kidney dysfunction. Prospective cohort study. Single tertiary-care university hospital. Forty-two adult patients having cardiac surgery with cardiopulmonary bypass. Intra-abdominal pressure (IAP) was measured preoperatively, immediately after surgery, and at the following time points after surgery: 3 hours, 6 hours, 12 hours, and 24 hours. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels were measured as a marker of kidney dysfunction at the following time points: prior to surgery, immediately after surgery, 4 to 6 hours after surgery, and 16-to-18 hours after surgery. Two hundred fifty-two IAPs were measured, and 90 (35.7%) showed IAH. Thirty-five of 42 patients (83.3%) had IAH at 1 time point or more. Peak urine NGAL levels were lower in patients with normal IAP (mean difference = -130.6 ng/mL [95% CI = -211.2 to -50.1], p = 0.002). There was no difference in postoperative kidney dysfunction by risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria in patients with normal IAP (mean difference = -31.4% [95% CI = -48.0 to 6.3], p = 0.09). IAH was 100% sensitive for predicting postoperative kidney dysfunction by RIFLE criteria, but had poor specificity (54.8%). IAH occurs frequently during the perioperative period in cardiac surgery patients and may be associated with postoperative kidney dysfunction.

Does maternal hydronephrosis have an impact on urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels?

Objective: To determine urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels and creatinine clearance values in women with different degrees of asymptomatic hydronephrosis during pregnancy.Methods: A total of 44 pregnant women with different degrees of hydronephrosis and 46 without hydronephrosis were consecutively enrolled in this prospective study. Basic serum and urine parameters, uNGAL levels, and creatinine clearance values were evaluated. All results were compared between the two groups. Regression analysis was used to determine independent predictors, which were mostly related to hydronephrosis.Results: Demographic data, basal laboratory parameters, and creatinine clearance values were similar, whereas significantly higher uNGAL levels were detected in women with hydronephrosis compared to those without hydronephrosis (45.3 versus 33.2 ng/mL, respectively) (p = 0.004). An increasing trend in uNGAL levels was detected with increasing degrees of hydronephrosis; as it was not statistically significant (p = 0.163). Linear regression analysis revealed that the parameter of “pelvic diameter” was found as a significant independent factor influencing uNGAL concentrations (β = 0.289; 95% CI: 0.522–3.061; p = 0.006). Other independent variables were not found to influence uNGAL concentrations (p > 0.05).Conclusion: The results obtained from this study indicate a significant increase of urinary concentration of NGAL in the presence of asymptomatic maternal hydronephrosis. This impact is likely to be more profound in those with severe hydronephrosis although this has not been specifically investigated. This theory needs to be validated in larger populations.

Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Patients with Obstructive Sleep Apnea.

BackgroundObstructive sleep apnea (OSA) is a well-established risk factor for hypertension and cardiovascular morbidity and mortality. More recently, OSA has been implicated as an independent risk factor for chronic kidney disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well-accepted early biomarker of subclinical kidney tubular injury, preceding an increase in serum creatinine. The goal of this study was to determine if an association exists between OSA and increased urinary NGAL levels.MethodsWe prospectively enrolled adult patients from the sleep clinic of an academic medical center. Each underwent polysomnography and submitted a urine specimen upon enrollment. We measured NGAL and creatinine levels on all urine samples before participants received treatment with continuous positive airway pressure (CPAP), and, in a subset of OSA patients, after CPAP therapy. We compared the urinary NGAL/creatinine ratio between untreated participants with and without OSA, and within a subset of 11 OSA patients also after CPAP therapy.ResultsA total of 49 subjects were enrolled: 16 controls based on an apnea-hypopnea index (events with at least 4% oxygen desaturation; AHI-4%) <5 events/hour (mean AHI-4% = 0.59 +/- 0.60); 33 OSA patients based on an AHI-4% >5 events/hour (mean AHI-4% = 43.3 +/- 28.1). OSA patients had a higher mean body-mass index than the control group (36.58 +/- 11.02 kg/m2 vs. 26.81 +/- 6.55 kg/m2, respectively; p = 0.0005) and were more likely to be treated for hypertension (54.5% vs. 6.25% of group members, respectively; p = 0.0014). The groups were otherwise similar in demographics, and there was no difference in the number of diabetic subjects or in the mean serum creatinine concentration (control = 0.86 +/- 0.15 mg/dl, OSA = 0.87 +/- 0.19 mg/dl; p = 0.7956). We found no difference between the urinary NGAL-to-creatinine ratios among untreated OSA patients versus control subjects (median NGAL/creatinine = 6.34 ng/mg vs. 6.41 ng/mg, respectively; p = 0.4148). Furthermore, CPAP therapy did not affect the urinary NGAL-to-creatinine ratio (p = 0.7758 for two-tailed, paired t-test).ConclusionsIn this prospective case-control study comparing patients with severe, hypoxic OSA to control subjects, all with normal serum creatinine, we found no difference between urinary levels of NGAL. Furthermore, CPAP therapy did not change these levels pre- and post-treatment.