Urinary neutrophil gelatinase-associated lipocalin determines short-term mortality and type of acute kidney injury in cirrhosis.
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ABSTRACT:
SUBMITTER: Udgirkar S
PROVIDER: S-EPMC7578274 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Urinary neutrophil gelatinase-associated lipocalin determines short-term mortality and type of acute kidney injury in cirrhosis.
Udgirkar Suhas S Rathi Pravin P Sonthalia Nikhil N Chandnani Sanjay S Contractor Qais Q Thanage Ravi R Jain Samit S
JGH open : an open access journal of gastroenterology and hepatology 20200703 5
<h4>Background and aim</h4>Acute kidney injury increases mortality in cirrhotic patients by four fold. This study aimed to determine the usefulness of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for differential diagnosis for acute kidney injury and for predicting short-term mortality in cirrhotic patients.<h4>Methods</h4>We enrolled 94 patients of decompensated cirrhosis. uNGAL was measured upon hospital admission in all patients. Patients with urinary tract infection and anuria ...[more]
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Project description:Background and aimsAcute kidney injury (AKI) commonly occurs in patients with decompensated cirrhosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) could help discriminate between different etiologies of AKI. The aim of this study was to investigate the use of uNGAL in (1) the differential diagnosis of AKI, (2) predicting the response to terlipressin and albumin in patients with hepatorenal syndrome-AKI (HRS-AKI), and (3) predicting in-hospital mortality in patients with AKI.Approach and resultsOne hundred sixty-two consecutive patients with cirrhosis and AKI were included from 2015 to 2020 and followed until transplant, death, or 90 days. Standard urinary markers and uNGAL were measured. Data on treatment, type, and resolution of AKI were collected. Thirty-five patients (21.6%) had prerenal AKI, 64 (39.5%) HRS-AKI, 27 (16.7%) acute tubular necrosis-AKI (ATN-AKI), and 36 (22.2%) a mixed form of AKI. Mean values of uNGAL were significantly higher in ATN-AKI than in other types of AKI (1162 ng/ml [95% CI 423-2105 ng/ml] vs. 109 ng/ml [95% CI 52-192 ng/ml]; p < 0.001). uNGAL showed a high discrimination ability in predicting ATN-AKI (area under the receiver operating characteristic curve, 0.854; 95% CI 0.767-0.941; p < 0.001). The best-performing threshold was found to be 220 ng/ml (sensitivity, 89%; specificity, 78%). The same threshold was independently associated with a higher risk of nonresponse (adjusted OR [aOR], 6.17; 95% CI 1.41-27.03; p = 0.016). In multivariable analysis (adjusted for age, Model for End-Stage Liver Disease, acute-on-chronic liver failure, leukocytes, and type of AKI), uNGAL was an independent predictor of in-hospital mortality (aOR, 1.74; 95% CI 1.26-2.38; p = 0.001).ConclusionsuNGAL is an adequate biomarker for making a differential diagnosis of AKI in cirrhosis and predicting the response to terlipressin and albumin in patients with HRS-AKI. In addition, it is an independent predictor of in-hospital mortality.
| S-EPMC10113003 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated.MethodsThis was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death.Main outcomesThirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h.ConclusionsMajority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation.Trial registrationThis was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )].
| S-EPMC8559408 | biostudies-literature
Project description:To determine the accuracy of the novel biomarker urinary neutrophil gelatinase-associated lipocalin (uNGAL) to diagnose urinary tract infections (UTIs) in febrile infants and young children. Prospective cross-sectional study of febrile infants <3 months ( ≥ 38.0°C) and children 3 to 24 months (≥ 39.0°C) evaluated for UTIs. uNGAL levels, urinalysis, Gram-stain and culture were obtained. UTI was defined by colony counts. Of 260 patients, 35 (13.5%) had UTIs. Median uNGAL levels were 215.1 ng/mL (interquartile range: 100.3-917.8) and 4.4 ng/mL (interquartile range: 1.6-11.8) in the groups diagnosed with and without UTIs, respectively. The area under the receiver-operating characteristic curve for uNGAL was 0.978 (95% confidence interval [CI]: 0.948-1.000). At a threshold uNGAL level of 39.1 ng/mL, sensitivity was 97.1% (95% CI: 83.4-99.9) and specificity was 95.6% (95% CI: 91.7-97.7). uNGAL had higher sensitivity than the combination of leukocyte esterase (in trace or greater amounts) or nitrite (+) (97.1%, 95% CI: 83.4-99.9 vs 74.3%, 95% CI: 56.4-86.9), with similar specificity (95.6%, 95% CI: 91.7-97.7 vs 97.3%, 95% CI: 94.0-98.9). uNGAL had higher sensitivity than Gram-stain (97.1%, 95% CI: 83.4-99.9 vs 74.3%, 95%: CI: 56.4-86.9), with similar specificity (95.6%, 95% CI: 91.7-97.7 vs 100.0%, 95% CI: 97.9-100.0). uNGAL has substantial accuracy to identify those with and without UTIs in infants and young children. Further studies will need to confirm our findings and determine if uNGAL is a more cost-effective test than standard screening tests.
| S-EPMC6658088 | biostudies-literature
Project description:BackgroundPlasma neutrophil gelatinase-associated lipocalin (pNGAL) has been investigated extensively in acute kidney injury. This study investigated its pathophysiological significance and utility as marker for graft failure and mortality in stable kidney transplant recipients (KTR).MethodsBaseline pNGAL was measured in 698 KTR (58% male, age 53 ± 13 years, estimated glomerular filtration rate 52.4 ± 20.4 mL/min/1.73 m2) at median 5.4 (interquartile range 1.8-12.0) years after transplantation, enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study.ResultspNGAL concentrations were higher in males, younger patients, patients with a deceased-donor kidney and higher serum creatinine. Independent of these, pNGAL was positively associated with urinary protein excretion, systemic inflammation parameters and calcineurin inhibitor use. During median follow-up of 5.3 (4.5-6.0) years, death-censored graft failure rates were 3.9%, 7.3% and 25.0% across increasing tertiles of pNGAL (Plog-rank < 0.001). Cox-regression analyses showed no independent associations of pNGAL with mortality, but strong associations with graft failure (hazard ratio, per doubling 4.16; 95% confidence interval 3.03-5.71; P < 0.001), which remained independent of adjustment for confounders. These associations were present only in patients with pre-existent proteinuria and poor kidney function.ConclusionspNGAL is associated with parameters of kidney graft damage and with graft failure. The latter association is particularly present in KTR with pre-existent poor kidney function and proteinuria. Trial Registration: ClinicalTrials.gov NCT02811835.
| S-EPMC8824800 | biostudies-literature
Project description:BackgroundThis study was conducted to determine whether there is an association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary transforming growth factor-β1 (uTGF-β1) with lupus nephritis (LN) disease activity.MethodsUrine samples from 18 LN patients were collected every month for six months then examined for uNGAL, uTGF-β1, and renal domain Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score.ResultsThe uNGAL levels were significantly different between active and inactive LN (P < 0.05). uTGF-β1 levels were not different between active and inactive LN (P < 0.05). There was a significant correlation between uNGAL levels and renal domain SLEDAI score (r = 0.417, P < 0.05). There was no correlation between uTGF-β1 levels and renal domain SLEDAI score (r = 0.031, P < 0.05).ConclusionuNGAL is better than uTGF-β1 for differentiation of active and inactive LN. uNGAL can be considered as a biomarker to monitor LN disease activity.
| S-EPMC4562555 | biostudies-literature
Project description: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.
| S-EPMC4858300 | biostudies-literature
Project description:To assess urine neutrophil gelatinase-associated lipocalin (uNGAL) level as a potential predictor of acute kidney injury (AKI), and both intensive care unit (ICU) and in-hospital mortality.Patients presenting to our ICU with a systolic blood pressure (SBP) less than 90 mmHg or mean arterial pressure (MAP) less than 65 mmHg, and no prior kidney disease were followed prospectively. Baseline data were collected on patient demographics, admission diagnosis, APACHE II and SOFA scores, SBP, MAP, serum creatinine and cystatin C, and uNGAL. Patients were monitored throughout hospitalization, including daily uNGAL, serum creatinine and cystatin C, and continuous MAP. Bivariate analysis compared those dying in the ICU and in-hospital versus survivors; with hierarchical binary logistic regression used to identify predictors of mortality. Areas under receiver-operating-characteristic curves (AUC) were used to measure sensitivity and specificity at different uNGAL thresholds.Among 75 patients followed, 16 died in the ICU, and another 24 prior to hospital discharge. Mortality rates were greatest in trauma and sepsis patients. The ICU survivors differed from non-survivors in almost all clinical variables; but only 2 predicted ICU mortality on multivariate analysis: day one uNGAL (p=0.01) and 24-hour APACHE II score (p=0.07). Only the APACHE II score significantly predicted in-hospital mortality (p=0.003). The AUC for day one uNGAL was greater for ICU (AUC=0.85) than in-hospital mortality (AUC=0.74).Day one uNGAL is a highly accurate predictor of ICU, but less so for in-hospital mortality.
| S-EPMC5556277 | biostudies-other
Project description:Backgrounds: Kidney biomarkers in urine appear to be useful in differential diagnosis between acute tubular necrosis and other types of acute kidney injury (AKI) in cirrhosis. In clinical practice, prerenal azotemia (PRA) is often distinguished from other types of AKI by volume expansion therapy. The aim of the current study was to investigate the accuracy of urinary biomarkers in the differential diagnosis between PRA and other types of AKI. Methods: A total of 65 patients with hepatitis B cirrhosis were prospectively included and divided into AKI and non-AKI groups. Patients with hepatitis B cirrhosis and AKI discontinue diuretics, vasodilators, and nephrotoxic drugs and give volume expansion therapy. The efficacy was judged after 48 h of treatment. Urinary biomarkers were measured at the time of diagnosis of AKI and 48 h after volume expansion therapy. Univariate and multivariate analyses were used to identify independent risk factors for nonresponse to volume expansion therapy. Results: Of the 65 patients, 49 patients with newly diagnosed AKI were screened in the study, and 16 hospitalized patients with hepatitis B cirrhosis without AKI at the same period were screened as the control group. In patients with cirrhosis and AKI, 29 (59.18%) patients were in the response group and 20 (40.81%) patients were in the nonresponse group. The mortality rate in the nonresponse group was significantly higher than that in the response group (75% vs. 13.8% p < 0.001). After logistic regression analysis, urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr) at diagnosis of AKI showed significant association with nonresponse to volume expansion therapy. The cutoff values for SCr and urinary NGAL were 128.50 µmol/L and 90.75 ng/ml, respectively. The area under the receiver operating curve (AUC) for SCr and urinary NGAL was 0.815 and 0.831. Conclusion: Elevated urinary NGAL can reflect the degree of kidney injury and is an independent risk factor for nonresponse to volume expansion therapy in patients with hepatitis B cirrhosis and AKI.
| S-EPMC9240615 | biostudies-literature
Project description:BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early prediction of renal damage and the progression of chronic kidney disease (CKD) in humans and dogs.HypothesisNeutrophil gelatinase-associated lipocalin also may play a role in the progression of CKD in cats.AnimalsEighty CKD and 18 control cats.MethodsCats were categorized into different stages according to the International Renal Interest Society (IRIS) staging system. Urine and plasma samples were collected and tested for NGAL concentrations using an in-house sandwich ELISA system and urinary NGAL (uNGAL)-to-creatinine ratio (UNCR) was determined. Cats in which serum creatinine concentration increased by >0.5 mg/dL from baseline within 30 days were defined as exhibiting progression.ResultsThe urinary NGAL and UNCR of CKD cats were significantly higher than those of healthy cats (P < .05) and were highly correlated with serum creatinine concentration. The area under the receiver operating characteristic curve (AUROC) for uNGAL, when predicting the progression of CKD, was 0.71 and the best cutoff value was 2.06 ng/mL with a sensitivity of 76.9% and a specificity of 75%. The AUROC for UNCR when predicting the progression of CKD was 0.79 and the best cutoff value was 4.08 × 10-6 with a sensitivity of 76.9% and specificity of 79.2%. Cats with UNCR values higher than their cutoffs experienced significantly faster deterioration with a median of 19 days.ConclusionsBoth urinary NGAL and UNCR are useful markers for the prediction of CKD progression in cats.
| S-EPMC5259624 | biostudies-literature
Project description:ObjectivesTo study the effects of running with/without the use of pain killers on urinary neutrophil gelatinase-associated lipocalin (uNGAL) and other parameters of kidney function in recreational runners.MethodsParticipants of the 10- and 21.1-km Weir Venloop race were enrolled and their urine samples collected before and after the run. Urine dipstick and other conventional tests used to assess kidney function were performed. The presence of ibuprofen, diclofenac, naproxen, and/or paracetamol was assessed by LC-MS/MS. uNGAL was measured with a two-step chemiluminescent immunoassay.ResultsNSAIDs/analgesics were detected in urine of 5 (14.4%) 10-km runners and 13 (28.9%) 21.1-km runners. Only half-marathon participants showed significant increases in uNGAL (pre: 11.7 [7.1-34.3] ng/mL; post: 33.4 [17.4-50.4] ng/mL; P = .0038). There was a significant effect of NSAID/analgesic use on uNGAL increase (F2, 76 = 4.210, P = .004). Post hoc tests revealed that uNGAL increased significantly in runners who tested positive for ibuprofen/naproxen compared to runners who did not use any medications (P = .045) or those who tested positive for paracetamol (P = .033). Running distance had a significant influence on the increase in uNGAL (F1, 53 = 4.741, P < .05), specific gravity (F1, 60 = 9.231, P < .01), urinary creatinine (F1, 61 = 10.574, P < .01), albumin (F1, 59 = 4.888, P < .05), and development of hematuria (χ2 (4) = 18.44, P = .001).ConclusionsRunning distance and use of ibuprofen/naproxen were identified as risk factors for uNGAL increase in recreational runners.
| S-EPMC7540343 | biostudies-literature