Inflammation-Associated Tubulopathy in Patients with Acute Bacterial Infections.

Background: Acute kidney injury associated with the underlying inflammatory process of an acute bacterial infection affects patient morbidity and mortality. Clinicians use creatinine and estimated glomerular filtration rate (EGFR) to assess this renal injury, however, these measures may lag behind and change only once significant kidney injury has occurred. Neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated by inflammation and infection and may serve as an early detection biomarker of kidney injury. Methods: Patients hospitalized with bacterial infections were assessed demographically, clinically and had their creatinine levels, EGFR and inflammatory biomarker levels, including urinary NGAL measured. Findings were compared between controls and patients across different EGFRs. Results: Fifty-one participants were included in the study. Among this cohort, 31 suffered bacterial infection. Inflammatory biomarkers including urinary NGAL were found to be higher in the infection group compared to the control group. Urinary NGAL level was significantly higher across all EGFRs of patients diagnosed with infection, including those with normal EGFR. Conclusion: Urinary NGAL identifies early kidney damage associated with bacterial infection even at normal EGFR and alerts the treating physician to undertake the necessary measures to mitigate the renal injury.

Early signaling of inflammation in patients following traumatic injury with accurately estimated time of injury by profiling C-reactive protein levels.

BACKGROUND: Despite its widespread use, the precise dynamics of CRP response in clinical practice remain poorly defined. We employed a novel quadratic model to explore the time-course analysis of CRP values in trauma patients with known precise time of injury. METHODS: Relevant data on all adult patients admitted to our hospital following traumatic incidents between January 1st 2010 to December 31, 2020 were retrospectively collected. Those with a documented time of injury and who underwent CRP evaluation within the first 24 h since injury were studied. RESULTS: Based on the findings from our annual health check-up center, we established a reference upper normal CRP value of 12.99 mg/L. Within the first 7 h after injury, the CRP levels of 8-9% of the 1545 study patients exceeded the reference threshold. The proportion of patients with CRP levels > 12.99 mg/L increased to 18.5% at 8-9 h later and rose sharply to 91.6% at 22-24 h later. Our quadratic model yielded the equation: CRP = 5.122-0.528xTime + 0.139xTime 2. It accounted for > 40% of the variance in CRP levels (R2 = 42.4%). CONCLUSIONS: Clear and prominent CRP elevations following atraumatic event are detected only 9-12 h following the insult. This novel finding has crucial implications for accurate CRP assessment of inflammatory responses to physical injuries.

Normoferremia in Patients with Acute Bacterial Infections-A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".

Impact of care bundles on the occurrence and outcomes of acute kidney injury among patients with ST-segment elevation myocardial infarction.

BACKGROUND: Several reports suggested that compliance with acute kidney injury care bundles among hospitalized patients resulted in improved kidney and patient outcomes. We investigated the effect of acute kidney injury care bundle utilization on the incidence of acute kidney injury and renal outcomes in a large cohort of myocardial infarction patients treated with percutaneous coronary intervention. METHODS: We included patients with myocardial infarction admitted following percutaneous coronary intervention between January 2008 and December 2020. From January 2016, acute kidney injury care bundle was implemented in our cardiac intensive care unit. Acute kidney injury care bundle consisted of simple standardized investigations and interventions, including strict monitoring of serum creatinine and urine analysis, planning investigations, treatment, and guidance about seeking nephrologist advice. Patients' records were evaluated for the occurrence of acute kidney injury, its severity, and recovery, before and after the implementation of acute kidney injury care bundle. RESULTS: We included 2646 patients (1941 patients in the years 2008-2015 and 705 patients in the years 2016-2020). Implementation of care bundles resulted in a significant decrease in the occurrence of acute kidney injury from 190/1945 to 42/705 (10-6%; p < 0.001), with a trend for lower acute kidney injury score > 1 (20% vs. 25%; p = 0.07) and higher acute kidney injury recovery (62% vs. 45%, p = 0.001). Using a multivariable regression model, the use of care bundles resulted in a 45% decrease in the relative risk for acute kidney injury (HR 0.55, 95% CI 0.37-0.82, p < 0.001). CONCLUSION: Among patients with ST-elevation myocardial infarction, treated with percutaneous coronary intervention and admitted to our cardiac intensive care unit over the period January 2008-December 2020, compliance with acute kidney injury care bundle was independently associated with a significant decrease in occurrence of acute kidney injury and with better renal outcomes following acute kidney injury. Further interventions, such as e-alert systems for acute kidney injury, could improve utilization of the acute kidney injury care bundle and optimize its clinical benefits.

Detection of Renal Injury Following Primary Coronary Intervention among ST-Segment Elevation Myocardial Infarction Patients: Doubling the Incidence Using Neutrophil Gelatinase-Associated Lipocalin as a Renal Biomarker.

BACKGROUND: A subgroup of patients with acute kidney injury (AKI) do not fulfil the functional criteria for AKI diagnosis but show elevated levels of new biomarkers reflecting tubular injury, suggesting that these patients suffer "subclinical AKI". We investigated the incidence and possible implications of "subclinical AKI", compared to no and clinical AKI among ST elevation myocardial infarction patients (STEMI) treated with primary coronary intervention (PCI). METHODS: We included 223 patients with STEMI treated with PCI. Neutrophil gelatinase-associated lipocalin (NGAL) was used as a marker of renal tubular damage in the absence of functional AKI, with NGAL levels ≥100 ng/mL suggesting subclinical AKI. Patients were assessed for the occurrence of in-hospital adverse outcomes. RESULTS: Of the study patients, 45 (25%) had subclinical AKI. These patients were more likely to have left ventricular ejection fraction ≤45% (33% vs. 23%. p = 0.01), in-hospital adverse outcomes (73% vs. 48%; p = 0.005), and a combination of the two. The multivariate regression model demonstrated that subclinical AKI was independently associated with in-hospital adverse outcomes (OR 3.71, 95% CI 1.30-10.62, p = 0.02). CONCLUSIONS: Subclinical AKI is common among STEMI patients and is independently associated with adverse outcomes, even in the absence of functional AKI.

Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Reversible versus Persistent Renal Tubular Damage in ST-Segment Myocardial Infarction Patients.

BACKGROUND: Most studies investigated the value of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of renal tubular injury only at a single time point. We investigated the possible utilization of NGAL level dynamics for the identification of different renal injury patterns in ST-elevation myocardial infarction (STEMI) patients. METHODS: Blood samples for plasma NGAL in 132 STEMI patients were drawn immediately before and 24 h following primary coronary intervention. Abnormal elevation of NGAL levels was defined using the cardiac surgery-associated NGAL score with NGAL levels ≥100 ng/mL suggesting renal tubular damage. According to NGAL levels at 0 and 24 h, patients were stratified into 3 groups: no tubular damage (NGAL <100 ng/mL in both exams), reversible tubular damage (NGAL >100 ng/mL at 0 h but <100 ng/mL at 24 h), and persistent tubular damage (NGAL >100 ng/mL at both 0 and 24 h). RESULTS: Mean age was 62 ± 13 years, and 78% were men. Of these patients, 29/132 (22%) demonstrated reversible tubular damage, and 36/132 (27%) persistent tubular damage. Only 13/132 patients (10%) progressed to clinical acute kidney injury during hospitalization, all of whom had persistent tubular injury. In multivariate regression model, symptom duration was independently associated with persistent tubular damage, both as continues variable (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04; p = 0.04) and for symptom duration >360 min (OR 2.66, 95% CI 1.07-6.63; p = 0.03). CONCLUSIONS: Renal tubular damage is common among STEMI patients. Dynamic NGAL measurement may differentiate between reversible and persistent tubular damage. Further trials are needed in order to assess the complex cardiorenal interactions.

Neutrophil Gelatinase-Associated Lipocalin for the Early Prediction of Acute Kidney Injury in ST-Segment Elevation Myocardial Infarction Patients Treated with Primary Percutaneous Coronary Intervention.

INTRODUCTION AND OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein released by renal tubular cells, can be used as a marker of early tubular damage. We evaluated plasma NGAL level utilization for the identification of acute kidney injury (AKI) among ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI). METHODS: 131 STEMI patients treated with PCI were prospectively included. Plasma NGAL levels were drawn prior to PCI (0 h) and 24 h afterwards. AKI was defined per KDIGO criteria of serum creatinine increase. Receiver-operating characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range. RESULTS: Overall AKI incidence was 14%. NGAL levels were significantly higher for patients with AKI at both 0 h (164 ± 42 vs. 95 ± 30; p < 0.001) and 24 h (142 ± 41 vs. 93 ± 36; p < 0.001). Per ROC curve analysis, an optimal cutoff value of NGAL (>120 ng/mL) predicted AKI with 80% sensitivity and specificity (AUC 0.881, 95%, CI 0.801-0.961, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI at 0 h (OR 1.044, 95% CI 1.013-1.076; p = 0.005) and 24 h (OR 1.018, 95% CI 1.001-1.036; p = 0.04). CONCLUSIONS: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Elevated neutrophil gelatinase-associated lipocalin levels before contrast media administration among ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released by renal tubular cells upon nephrotoxic or ischemic events and is considered an early marker of tubular damage. We aimed to demonstrate the presence of early renal injury detected by elevated NGAL levels taken before contrast administration in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). PATIENTS AND METHODS: We prospectively included 88 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (baseline NGAL; NGAL1) and 24 h after PCI (NGAL2). Abnormal elevations in NGAL levels were defined using the cardiac surgery associated NGAL score (NGAL score) with NGAL levels at least 100 ng/ml, suggesting renal tubular damage. Patients were also assessed for the dynamics between NGAL2 and NGAL1 levels. RESULTS: The mean age of the patients was 62 ± 13 years and 78% were men. A total of 50/88 (56%) patients had baseline NGAL level of at least 100, suggesting possible tubular damage before PCI. Only 10 patients progressed to clinical acute kidney injury during hospitalization, all of whom had baseline NGAL level of at least 100 (P < 0.001). Among patients with baseline NGAL at least 100, 28/50 (56%) showed a decrease in the NGAL level within 24 h, whereas only 9/50 (18%) showed an elevation in the NGAL level. In contrast, only 7/38 (19%) patients with baseline NGAL level less than 100 showed an elevation in NGAL levels within 24 h. CONCLUSION: Elevated NGAL levels before primary PCI suggesting renal tubular damage are common among STEMI patients. Further trials are needed to assess the complex cardio-renal interactions.

Induced sputum eosinophilia in ulcerative colitis patients: the lung as a mirror image of intestine?

BACKGROUND: Ulcerative colitis (UC) is a systemic disease of unknown etiology with extra-intestinal manifestation. Induced sputum (IS) non-invasively assesses extrapulmonary involvement in Crohn's disease. We sought to determine whether there is a cellular marker of lung injury in UC patients detectable by IS. METHODS: Nineteen UC patients (mean age 46.4+/-11.3 years, disease duration 8.6+/-7.5 years [range 1-25 years] 68.4% males) were studied, 6 with active disease and 13 in remission. Eleven received 5-ASA, 5 received steroids and/or azathioprine and 3 patients were untreated. UC patients were compared with 27 healthy non-smoker controls. IS was recovered after 20 min inhalation of 3% saline with an ultrasonic nebulizer by the selecting plugs method, and 300 cells were differentially cell counted in cytospin Giemsa-stained slides. CD4/CD8 subsets were identified by FACS. Pulmonary function tests were performed by the Jaeger Masterlab spirometer. RESULTS: UC patients' IS contained higher %eosinophils than controls (p=0.05) and lower FEV(1)/FVC ratios (p=0.001). Steroid- and/or azathioprine-treated patients had significantly lower FEV(1)/FVC ratios than only 5-ASA-treated patients (p=0.019). Eosinophil infiltration in airways was high in 5-ASA-treated patients compared to those receiving steroids and/or azathioprine (p=0.046) and those with less extensive disease (p=0.05). Using a cutoff of 3% eosinophils, IS had a sensitivity of 67% and specificity of 73% to differentiate patients with a cutoff of 70 eosinophils/mm(2) in biopsy. CONCLUSIONS: The percentage of sputum eosinophils is significantly different between UC patients with proctitis and pancolitis. These immune abnormalities may be a common pattern that is present throughout the mucosae.

Hydrogen peroxide in exhaled breath condensate (EBC) vs eosinophil count in induced sputum (IS) in parenchymal vs airways lung diseases.

We compared exhaled breath condensate (EBC) and induced sputum (IS) for assessing inflammation in pulmonary diseases in patients with obstructive lung disease (n = 20), persistent cough >6 months (n = 20), interstitial lung disease (n = 25) and controls (n = 10). EBC was collected by suspending a Teflon perfluoroalkoxy tube installed in an ice-filled container and connected to a polypropylene test tube. IS was recovered after 20' inhalation of 3% saline with an ultrasonic nebulizer, and 300 cells were differentially counted in cytospin Giemsa-stained slides. H(2)0(2) was measured by a method based on oxidation of phenolsulfonphthalein (phenol red) mediated by horseradish peroxidases and H(2)0(2). Pulmonary function tests were performed by conventional methods. H(2)0(2) levels in EBC and % eosinophils in IS were significantly different between groups. A positive and significant correlation was found between % eosinophils in IS and the levels of H(2)0(2) in EBC for each group and for all patients combined.