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Systemic Human Neutrophil Lipocalin Associates with Severe Acute Kidney Injury in SARS-CoV-2 Pneumonia.

ABSTRACT: Neutrophils have been suggested mediators of organ dysfunction in COVID-19. The current study investigated if systemic neutrophil activity, estimated by human neutrophil lipocalin (HNL) concentration in peripheral blood, is associated with acute kidney injury (AKI) development. A total of 103 adult patients admitted to intensive care, with PCR-confirmed SARS-CoV-2 infection, were prospectively included (Clinical Trials ID: NCT04316884). HNL was analyzed in plasma (P-HNL Dimer) and in whole blood (B-HNL). The latter after ex vivo activation with N-formyl-methionine-leucine-phenylalanine. All patients developed respiratory dysfunction and 62 (60%) were treated with invasive ventilation. Sixty-seven patients (65%) developed AKI, 18 (17%) progressed to AKI stage 3, and 14 (14%) were treated with continuous renal replacement therapy (CRRT). P-HNL Dimer was higher in patients with invasive ventilation, vasopressors, AKI, AKI stage 3, dialysis, and 30-day mortality (p < 0.001-0.046). B-HNL performed similarly with the exception of mild AKI and mortality (p < 0.001-0.004). The cohort was dichotomized by ROC estimated cutoff concentrations of 13.2 µg/L and 190 µg/L for P-HNL Dimer and B-HNL respectively. Increased cumulative risks for AKI, AKI stage 3, and death were observed if above the P-HNL cutoff and for AKI stage 3 if above the B-HNL cutoff. The relative risk of developing AKI stage 3 was nine and 39 times greater if above the cutoffs in plasma and whole blood, respectively, for CRRT eight times greater for both. In conclusion, systemically elevated neutrophil lipocalin, interpreted as increased neutrophil activity, was shown to be associated with an increased risk of severe AKI, renal replacement therapy, and mortality in COVID-19 patients with respiratory failure.

SUBMITTER: Bulow Anderberg S

PROVIDER: S-EPMC8464787 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Systemic Human Neutrophil Lipocalin Associates with Severe Acute Kidney Injury in SARS-CoV-2 Pneumonia.

Bülow Anderberg Sara S Lipcsey Miklos M Hultström Michael M Eriksson Ann-Katrin AK Venge Per P Frithiof Robert R On Behalf Of The Uppsala Intensive Care Covid-Research Group

Journal of clinical medicine 20210914 18

Neutrophils have been suggested mediators of organ dysfunction in COVID-19. The current study investigated if systemic neutrophil activity, estimated by human neutrophil lipocalin (HNL) concentration in peripheral blood, is associated with acute kidney injury (AKI) development. A total of 103 adult patients admitted to intensive care, with PCR-confirmed SARS-CoV-2 infection, were prospectively included (Clinical Trials ID: NCT04316884). HNL was analyzed in plasma (P-HNL Dimer) and in whole blood ...[more]

PMID: 34575252

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Project description:PurposeWe evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls.Materials and methodsUsing patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater.ResultsOf 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate.ConclusionsUrine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.

Project description:BackgroundFew studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin.MethodsParticipants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher).ResultsOf 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65).ConclusionsUrine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

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 )].

Project description:Background and aimsAcute kidney injury (AKI) increases mortality in cirrhosis. Early identification of the cause of AKI helps in planning appropriate management. We aimed to find whether neutrophil gelatinase-associated lipocalin (NGAL) can be used to differentiate between different types of AKI in cirrhosis and predict short-term outcomes in patients with decompensated cirrhosis and AKI.MethodThis was a time-bound study in which consecutive hospitalized patients with cirrhosis and AKI were prospectively recruited and managed as per standard care. Acute on chronic liver failure (ACLF) was diagnosed as per the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) criteria. Urine NGAL was measured by enzyme-linked immunosorbent assay (ELISA) by Epitope Diagnostics Inc. kit (San Diego, USA.) in all patients on admission, and patients were followed up until hospital discharge or death.ResultsA total of 110 consecutive patients (median [range] age: 44 [28-81] years;87.3%were male; ACLF: 71.8%; acute decompensation 28.2%; Model for end-stage liver disease (MELD) 27 [13-46]; Child-Turcotte-Pugh (CTP) 11 [7-15]) with cirrhosis and AKI were recruited. Alcohol was the most common etiology of cirrhosis(64.5%)). Pre-renal azotemia (PRA) was the most common cause of AKI (n = 56). Urine NGAL was significantly elevated in acute tubular necrosis (ATN) (1747 [6-6141] ng/ml than in hepatorenal syndrome (HRS) (379 [33.5-2320] ng/ml; P < 0.0001) and PRA (167 ng/ml [3.34-660]; P < 0.0001). Sixty-four percent patients with ATN, 27.6% patients with HRS, and none with PRA required dialysis. A total of 79.31% patients with HRS and 76% with ATN died. Urine NGAL was significantly higher in patients who required hemodialysis than in those who did not (1733 [243-6141] ng/ml vs 235 [3.34-2320] ng/ml; P < 0.0001). Both urine NGAL (n = 110) and plasma NGAL (n = 90) were significantly higher in patients who died (urine NGAL: -475 [6-6141] ng/ml vs 247 [3.34-2320] ng/ml; P = 0.002;plasma NGAL-950 [94-4859] ng/ml vs 608 [18-3300)]g/ml; P < 0.001). On multivariate analysis, urine NGAL and INR could predict mortality.ConclusionNGAL can differentiate between different types of AKI in cirrhosis and predict the need for hemodialysis and mortality in decompensated cirrhosis with AKI.

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Systemic Human Neutrophil Lipocalin Associates with Severe Acute Kidney Injury in SARS-CoV-2 Pneumonia.

Publications

Systemic Human Neutrophil Lipocalin Associates with Severe Acute Kidney Injury in SARS-CoV-2 Pneumonia.

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