Aims: Measurement of B-type natriuretic peptide (BNP) or N-terminal pro-BNP is recommended as part of the diagnostic workup of patients with suspected heart failure (HF). We evaluated the diagnostic and prognostic utility of the novel urinary proteomic classifier HF1, compared with BNP, in HF. HF1 consists of 85 unique urinary peptide fragments thought, mainly, to reflect collagen turnover.
View Article and Find Full Text PDFRationale: The urinary proteome reflects molecular drivers of disease.
Objectives: To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality.
Methods: In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis coupled with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL), and urinary albumin.
Kidney function is altered by age together with a declined filtration capacity of 5-10% per decade after 35 years. Renal aging shares many characteristics with chronic kidney disease. Plasma levels of the bioactive peptide apelin also decline with age and apelin has been shown to be protective in chronic kidney disease.
View Article and Find Full Text PDFDiastolic heart failure (DHF) is characterized by slow left ventricular (LV) relaxation, increased LV stiffness, interstitial deposition of collagen, and a modified extracellular matrix proteins. Among Europeans, the frequency of asymptomatic diastolic LV dysfunction (DD) is 25%. This constitutes a large pool of people at high risk of DHF.
View Article and Find Full Text PDFObjectives: Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature.
Methods: In 336 HTx patients (mean age, 56.
Nephrol Dial Transplant
August 2019
Background: Chronic kidney disease (CKD) is common in patients after heart transplantation (HTx). We assessed whether in HTx recipients the proteomic urinary classifier CKD273 or sequenced urinary peptides revealing the parental proteins correlated with the estimated glomerular filtration rate (eGFR).
Methods: In 368 HTx patients, we measured the urinary peptidome and analysed CKD273 and 48 urinary peptides with a detectable signal in >95% of participants.
Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.
Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.
Hypertension, obesity, and old age are major risk factors for left ventricular (LV) diastolic dysfunction (LVDD), but easily applicable screening tools for people at risk are lacking. We investigated whether HF1, a urinary biomarker consisting of 85 peptides, can predict over a 5-year time span mildly impaired diastolic LV function as assessed by echocardiography. In 645 white Flemish (50.
View Article and Find Full Text PDFObjectives: Urinary Proteomics in Predicting Heart Transplantation Outcomes (uPROPHET; NCT03152422) aims: (i) to construct new multidimensional urinary proteomic (UP) classifiers that after heart transplantation (HTx) help in detecting graft vasculopathy, monitoring immune system activity and graft performance, and in adjusting immunosuppression; (ii) to sequence UP peptide fragments and to identify key proteins mediating HTx-related complications; (iii) to validate UP classifiers by demonstrating analogy between UP profiles and tissue proteomic signatures (TP) in diseased explanted hearts, to be compared with normal donor hearts; (iv) and to identify new drug targets. This article describes the uPROPHET database construction, follow-up strategies and baseline characteristics of the HTx patients.
Methods: HTx patients enrolled at the University Hospital Gasthuisberg (Leuven) collected mid-morning urine samples.
Background: Detection of preclinical cardiac dysfunction and prognosis of left ventricular heart failure (HF) would allow targeted intervention, and appears to be the most promising approach in its management. Novel biomarker panels may support this approach and provide new insights into the pathophysiology.
Methods And Results: A retrospective comparison of urinary proteomic profiles generated by mass spectrometric analysis from 49 HF patients, 36 patients who progressed to HF within 2.
Identification of individuals who are at risk of suffering from acute coronary syndromes (ACS) may allow to introduce preventative measures. We aimed to identify ACS-related urinary peptides, that combined as a pattern can be used as prognostic biomarker. Proteomic data of 252 individuals enrolled in four prospective studies from Australia, Europe and North America were analyzed.
View Article and Find Full Text PDFAgeing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans.
View Article and Find Full Text PDFClinical proteomics aims at the development and the implementation of novel biomarkers that demonstrate a clear clinical benefit in the management of diseases. However, though the attention in the field is increasing and multiple articles on biomarker research are published, clinical implementation of these biomarkers is scarce. In this paper, we aim towards identifying the hurdles on the path towards implementation, and present one successful approach, based on capillary electrophoresis coupled with mass spectrometry.
View Article and Find Full Text PDFBackground: When combined with a clinical outcome variable, the size, complexity and nature of mass-spectrometry proteomics data impose great statistical challenges in the discovery of potential disease-associated biomarkers. The purpose of this study was thus to evaluate the effectiveness of different statistical methods applied for urinary proteomic biomarker discovery and different methods of classifier modelling in respect of the diagnosis of coronary artery disease in 197 study subjects and the prognostication of acute coronary syndromes in 368 study subjects.
Results: Computing the discovery sub-cohorts comprising [Formula: see text] of the study subjects based on the Wilcoxon rank sum test, t-score, cat-score, binary discriminant analysis and random forests provided largely different numbers (ranging from 2 to 398) of potential peptide biomarkers.
Background: Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF.
Methods And Results: Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles.
To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinarypeptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.
View Article and Find Full Text PDFBased on demographic trends, the societies in many developed countries are facing an increasing number and proportion of people over the age of 65. The raise in elderly populations along with improved health-care will be concomitant with an increased prevalence of ageing-associated chronic conditions like cardiovascular, renal, and respiratory diseases, arthritis, dementia, and diabetes mellitus. This is expected to pose unprecedented challenges both for individuals and societies and their health care systems.
View Article and Find Full Text PDFChronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms.
View Article and Find Full Text PDFJ Microbiol Methods
April 2013
Viability PCR (v-PCR) as a method to selectively detect intact live cells has gained considerable interest over the last years with an increasing number of applications. The principle is based on treatment of microbiological samples with a viability dye prior to extraction of genomic DNA and its amplification. The dye is selectively taken up by membrane-compromised dead cells resulting in the degradation of their DNA upon light exposure and therefore inhibition of amplification.
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