Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure.
Ontology highlight
ABSTRACT:
SUBMITTER: Templeton EM
PROVIDER: S-EPMC8778509 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:A quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI), an abrupt loss of kidney function that doubles the risk of death at one-year. There is a critical need to identify early markers for AKI in ADHF, however, no protein candidates have been validated as diagnostic or prognostic biomarkers in this setting. We aimed to identify novel candidate protein biomarkers by quantifying changes in protein expression in the kidney that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using Sequential Window Acquisition of All Theoretical Mass Spectrometry (SWATH-MS) in kidney cortex from healthy control sheep (n=5), sheep with established rapid pacing-induced ADHF (n=8) and sheep after ~4 weeks recovery from ADHF (n=7). Of 790 proteins quantified, we identified 17 candidate kidney injury markers, one potential marker of kidney recovery and two markers of long-term renal impairment that were differentially expressed between groups (1.2-2.6 fold-change, p<0.05). Differentially expressed proteins were enriched in pro-inflammatory signaling pathways: Glycoprotein VI (activated during ADHF development, adjusted p<0.01) and acute phase response (repressed during recovery from ADHF, p<0.01). This research identified 20 candidate protein markers of kidney injury, including 6 promising candidates supported by existing evidence and 14 novel candidates never implicated in AKI. Early awareness of AKI in ADHF through the use of biomarkers has the potential to reduce mortality and improve outcomes for these at-risk patients.
2022-01-19 | PXD028983 | Pride
Project description:Background Renal function in acute decompensated heart faiulre (ADHF) is a strong predictor of disease evolution and poor outcome. Current biomarkers for early diagnostic of renal injury in the setting of ADHF are still controversial, and their association to early pathological changes needs to be established. By applying a proteomic approach, we aimed to identify early changes in the differential urine protein signature associated with development of renal injury in patients hospitalised due to ADHF. Materials and Methods Patients (71 [64–77] years old) admitted at the emergency room with ADHF and hospitalised were investigated (N = 64). Samples (urine/serum) were collected at hospital admission (day 0) and 72 h later (day 3). Differential serum proteome was analysed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight (MALDI-ToF/ToF). Validation studies were performed using ELISA. Results Proteomic analysis depicted urinary vitamin D binding protein (uVDBP) as a two spots protein with increased intensity in ADHF and significant differences depending on the glomerular filtration rate (GFR). Urinary VDBP in patients with ADHF at hospitalisation was > threefold higher than in healthy subjects, with the highest levels in those patients with ADHF already presenting renal dysfunction. At day 3, urine VDBP levels in patients maintaining normal renal function dropped to normal values (P = 0.03 vs. day 0). In contrast, urine VDBP levels remained elevated in the group developing renal injury, with values twofold above the normal range (P < 0.05), while serum creatinine and GF levels were within the physiological range in this group. Urinary VDBP in ADHF positively correlated with markers of renal injury such as cystatin C and Kidney Injury Molecule 1 (KIM-1). By ROC analysis, urinary VDBP, when added to cystatin C and KIM-1, improved the prediction of renal injury in patients with ADHF. Conclusion We showed increased urine VDBP in patients with ADHF at hospital admission and a differential uVDBP evolution pattern at early stage of renal dysfunction, before pathological worsening of GFR is evidenced.
| S-EPMC9222131 | biostudies-literature
Project description:BackgroundIn acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP-2] × [IGFBP7], a new US Food and Drug Administration-cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients.HypothesisIn patients with ADHF, urinary [TIMP-2] × [IGFBP7] is associated with moderate to severe AKI and related to increased mortality.MethodsWe enrolled 400 patients in the emergency department at Robert-Bosch Hospital, Stuttgart, Germany. We examined the predictive ability of urinary [TIMP-2] × [IGFBP7] (units: [ng/mL]2 /1000) for development of AKI stage 2 or 3 within 24 hours of sample collection in patients with ADHF. Operating characteristics were determined for the validated cutoffs of 0.3 and 2.0.ResultsForty patients had ADHF upon presentation and sufficient data for AKI staging. 27.5% developed AKI stage 2-3 within 7 days. Urinary [TIMP-2] × [IGFBP7] discriminated for AKI stage 2-3 over the first day with an area under the ROC curve of 0.84 (95% confidence interval: 0.72-0.93) and over 7 days with an AUC of 0.77 (95% confidence interval: 0.65-0.88). For the first day, sensitivity was 86% at the 0.3 cutoff and specificity was 95% at the 2.0 cutoff for prediction of AKI stage 2-3. There was a trend (P = 0.08) for higher mortality in patients with urinary [TIMP-2] × [IGFBP7] >2.0 and AKI 2-3.ConclusionsUrinary [TIMP-2] × [IGFBP7] is a promising marker for AKI risk assessment in patients with ADHF.
| S-EPMC6490429 | biostudies-literature
Project description:Background: Acute kidney injury is an adverse event that carries significant morbidity among patients with acute decompensated heart failure (ADHF). We planned to develop a parsimonious model that is simple enough to use in clinical practice to predict the risk of acute kidney injury (AKI) occurrence. Methods: Six hundred and fifty patients with ADHF were enrolled in this study. Data for each patient were collected from medical records. We took three different approaches of variable selection to derive four multivariable logistic regression model. We selected six candidate predictors that led to a relatively stable outcome in different models to derive the final prediction model. The prediction model was verified through the use of the C-Statistics and calibration curve. Results: Acute kidney injury occurred in 42.8% of the patients. Advanced age, diabetes, previous renal dysfunction, high baseline creatinine, high B-type natriuretic peptide, and hypoalbuminemia were the strongest predictors for AKI. The prediction model showed moderate discrimination C-Statistics: 0.766 (95% CI, 0.729-0.803) and good identical calibration. Conclusion: In this study, we developed a prediction model and nomogram to estimate the risk of AKI among patients with ADHF. It may help clinical physicians detect AKI and manage it promptly.
| S-EPMC8634389 | biostudies-literature
Project description:Background and objectivesThe thick perirenal fat pad can induce high intracapsular pressure and cause compression of the renal vasculature and resultant congestive nephropathy. The current study investigated the association of perirenal fat thickness with kidney dysfunction in patients with acute decompensated heart failure (ADHF).MethodsData from 266 patients hospitalized with ADHF were analyzed. Patients were divided into two groups according to the glomerular filtration rate (GFR) at admission (preserved kidney function [GFR ≥60 mL/min/1.73 m2] and reduced kidney function [GFR <60 mL/min/1.73 m2] groups). Right and left posterior perirenal fat thicknesses were measured using computed tomography, and their average values were calculated. Associated factors with reduced kidney function was assessed by logistic regression model, presenting with odds ratio (OR) and confidence interval (CI).ResultsIncreasing age (OR, 1.08; 95% CI, 1.04-1.12; p<0.001), diabetes mellitus (OR, 2.46; 95% CI, 1.18-5.12; p<0.017), increased log N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR, 1.82; 95% CI, 1.32-2.52; p<0.001), and increased average perirenal fat thickness (OR, 1.11; 95% CI, 1.06-1.16; p<0.001) were independently associated with reduced kidney function. In the subgroup analyses, patients over 70 years old, the ratio of mitral-to-mitral annular velocity >15, elevated log NT-proBNP had a significantly higher association with increased perirenal fat thickness with reduced kidney function.ConclusionsThick perirenal fat pads were independently associated with kidney function deterioration in patients hospitalized with ADHF.
| S-EPMC9902646 | biostudies-literature
Project description:BackgroundHeart failure is one of the most common diseases of adults in Europe, with an overall prevalence of 1-2%. Among persons aged 60 and above, its prevalence is above 10% in men and 8% in women. Acute heart failure has a poor prognosis; it is associated with a high rate of rehospitalization and a 1-year mortality of 20-30%.MethodsThis review is based on pertinent literature, including guidelines, retrieved by a selective search in PubMed.ResultsThere are different types of acute heart failure; the basic diagnostic assessment is performed at once and consists of ECG, echocardiography, and the measurement of N-terminal pro-brain natriuretic peptide (NTproBNP) and troponin levels. The most common causes of decompensation are arrhythmia, valvular dysfunction, and acute cardiac ischemia, each of which accounts for 30% of cases. The potential indication for immediate revascularization should be carefully considered in cases where acute heart failure is due to coronary heart disease. The basic treatment of acute heart failure is symptomatic, with the administration of oxygen, diuretics, and vasodilators. Ino-tropic agents, vasopressors, and temporary mechanical support for the circulatory system are only used to treat cardiogenic shock.ConclusionThe treatment of acute heart failure is markedly less evidence-based than that of chronic heart failure. Newer treatment approaches that are intended to improve outcomes still need to be tested in multicenter trials.
| S-EPMC4452901 | biostudies-literature
Project description:The aim of this study was to characterize iron deficiency (ID) in acutely decompensated heart failure (ADHF) and identify whether ID is associated with dyspnea class, length of stay (LOS), biomarker levels, and echocardiographic indices of diastolic function in patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Consecutive patients admitted with ADHF at a single tertiary center were included. Demographic information, pathology investigations, and metrics regarding hospital stay and readmission were recorded. Patients were classified as having 'absolute' ID if they had a ferritin level <100 ng/mL; or 'functional' ID if they had a ferritin 100-200 ng/mL and a transferrin saturation <20%. Of 503 patients that were recruited, 270 (55%) had HFpEF, 160 (33%) had HFREF, and 57 (12%) had heart failure with mid-range ejection fraction. ID was present in 54% of patients with HFrEF and 56% of patients with HFpEF. In the HFpEF group, ID was associated with a LOS of 11 ± 7.7 vs. 9 ± 6 days in iron replete patients, p = 0.036, and remained an independent predictor of increased LOS in a multivariate linear regression incorporating comorbidities, age, and ID status. This study corroborates a high prevalence of ID in both HFrEF and HFpEF, and further shows that in patients with HFpEF there is a prolongation of LOS not seen in HFrEF which may indicate a more prominent role for ID in HFpEF.
| S-EPMC6832529 | biostudies-literature
Project description:ObjectivesThis study sought to determine the use of intravenous fluids in the early care of patients with acute decompensated heart failure (HF) who are treated with loop diuretics.BackgroundIntravenous fluids are routinely provided to many hospitalized patients.MethodsWe conducted a retrospective cohort study of patients admitted with HF to 346 hospitals from 2009 to 2010. We assessed the use of intravenous fluids during the first 2 days of hospitalization. We determined the frequency of adverse in-hospital outcomes. We assessed variation in the use of intravenous fluids across hospitals and patient groups.ResultsAmong 131,430 hospitalizations for HF, 13,806 (11%) were in patients treated with intravenous fluids during the first 2 days. The median volume of administered fluid was 1,000 ml (interquartile range: 1,000 to 2,000 ml), and the most commonly used fluids were normal saline (80%) and half-normal saline (12%). Demographic characteristics and comorbidities were similar in hospitalizations in which patients did and did not receive fluids. Patients who were treated with intravenous fluids had higher rates of subsequent critical care admission (5.7% vs. 3.8%; p < 0.0001), intubation (1.4% vs. 1.0%; p = 0.0012), renal replacement therapy (0.6% vs. 0.3%; p < 0.0001), and hospital death (3.3% vs. 1.8%; p < 0.0001) compared with those who received only diuretics. The proportion of hospitalizations that used fluid treatment varied widely across hospitals (range: 0% to 71%; median: 12.5%).ConclusionsMany patients who are hospitalized with HF and receive diuretics also receive intravenous fluids during their early inpatient care, and the proportion varies among hospitals. Such practice is associated with worse outcomes and warrants further investigation.
| S-EPMC4438991 | biostudies-literature
Project description:BackgroundStudies have shown that more than half of patients with heart failure (HF) with acute kidney injury (AKI) have newonset AKI, and renal function evaluation markers such as estimated glomerular filtration rate are usually not repeatedly tested during the hospitalization. As an independent risk factor, delayed AKI recognition has been shown to be associated with the adverse events of patients with HF, such as chronic kidney disease and death.ObjectiveThe aim of this study is to develop and assess of an unsupervised machine learning model that identifies patients with HF and normal renal function but who are susceptible to de novo AKI.MethodsWe analyzed an electronic health record data set that included 5075 patients admitted for HF with normal renal function, from which 2 phenogroups were categorized using an unsupervised machine learning algorithm called K-means clustering. We then determined whether the inferred phenogroup index had the potential to be an essential risk indicator by conducting survival analysis, AKI prediction, and the hazard ratio test.ResultsThe AKI incidence rate in the generated phenogroup 2 was significantly higher than that in phenogroup 1 (group 1: 106/2823, 3.75%; group 2: 259/2252, 11.50%; P<.001). The survival rate of phenogroup 2 was consistently lower than that of phenogroup 1 (P<.005). According to logistic regression, the univariate model using the phenogroup index achieved promising performance in AKI prediction (sensitivity 0.710). The generated phenogroup index was also significant in serving as a risk indicator for AKI (hazard ratio 3.20, 95% CI 2.55-4.01). Consistent results were yielded by applying the proposed model on an external validation data set extracted from Medical Information Mart for Intensive Care (MIMIC) III pertaining to 1006 patients with HF and normal renal function.ConclusionsAccording to a machine learning analysis on electronic health record data, patients with HF who had normal renal function were clustered into separate phenogroups associated with different risk levels of de novo AKI. Our investigation suggests that using machine learning can facilitate patient phengrouping and stratification in clinical settings where the identification of high-risk patients has been challenging.
| S-EPMC9617187 | biostudies-literature
Project description:BackgroundLoop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.MethodsIn a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.ResultsIn the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 μmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.ConclusionsAmong patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).
| S-EPMC3412356 | biostudies-literature