Recent Advances of Proteomics in Management of Acute Kidney Injury.

Acute Kidney Injury (AKI) is currently recognized as a life-threatening disease, leading to an exponential increase in morbidity and mortality worldwide. At present, AKI is characterized by a significant increase in serum creatinine (SCr) levels, typically followed by a sudden drop in glomerulus filtration rate (GFR). Changes in urine output are usually associated with the renal inability to excrete urea and other nitrogenous waste products, causing extracellular volume and electrolyte imbalances.

A Model to Detect Significant Prostate Cancer Integrating Urinary Peptide and Extracellular Vesicle RNA Data.

There is a clinical need to improve assessment of biopsy-naïve patients for the presence of clinically significant prostate cancer (PCa). In this study, we investigated whether the robust integration of expression data from urinary extracellular vesicle RNA (EV-RNA) with urine proteomic metabolites can accurately predict PCa biopsy outcome. Urine samples collected within the Movember GAP1 Urine Biomarker study (n = 192) were analysed by both mass spectrometry-based urine-proteomics and NanoString gene-expression analysis (167 gene-probes).

Pathophysiological Implications of Urinary Peptides in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is known to be associated with protein alterations and extracellular fibrous deposition. We investigated the urinary proteomic profiles of HCC patients in this prospective cross sectional multicentre study. 195 patients were recruited from the UK (Coventry) and Germany (Hannover) between 1 January 2013 and 30 June 2019.

Discovery, validation and sequencing of urinary peptides for diagnosis of liver fibrosis-A multicentre study.

Background: Liver fibrosis is a consequence of chronic inflammation and is associated with protein changes within the hepatocytes structure. In this study, we aimed to investigate if this is reflected by the urinary proteome and can be explored to diagnose liver fibrosis in patients with chronic liver disease.

Methods: In a multicentre combined cross-sectional and prospective diagnostic test validation study, 129 patients with varying degrees of liver fibrosis and 223 controls without liver fibrosis were recruited.

Peptides in Plasma, Urine, and Dialysate: Toward Unravelling Renal Peptide Handling.

Purpose: The peptidomes of spent hemodialysate, urine, and plasma are investigated, to shed light on peptide handling in the kidney.

Experimental Design: Fifteen plasma, 15 urine, and 13 spent hemodialysate samples are collected from age- and sex-matched subjects with chronic kidney disease. Peptide identification and quantification are performed with capillary electrophoresis-coupled mass spectrometry.

Bile and urine peptide marker profiles: access keys to molecular pathways and biological processes in cholangiocarcinoma.

Background: Detection of cholangiocarcinoma (CCA) remains a diagnostic challenge. We established diagnostic peptide biomarkers in bile and urine based on capillary electrophoresis coupled to mass spectrometry (CE-MS) to detect both local and systemic changes during CCA progression. In a prospective cohort study we recently demonstrated that combined bile and urine proteome analysis could further improve diagnostic accuracy of CCA diagnosis in patients with unknown biliary strictures.

The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease.

Background: The urinary proteomic classifier chronic kidney disease 273 (CKD273) is predictive for the development and progression of chronic kidney disease (CKD) and/or albuminuria in type 2 diabetes. This study evaluates its role in the prediction of cardiovascular (CV) events in patients with CKD Stages G1-G5.

Methods: We applied the CKD273 classifier in a cohort of 451 patients with CKD Stages G1-G5 followed prospectively for a median of 5.

Urinary peptide panel for prognostic assessment of bladder cancer relapse.

Non-invasive tools stratifying bladder cancer (BC) patients according to the risk of relapse are urgently needed to guide clinical intervention. As a follow-up to the previously published study on CE-MS-based urinary biomarkers for BC detection and recurrence monitoring, we expanded the investigation towards BC patients with longitudinal data. Profiling datasets of BC patients with follow-up information regarding the relapse status were investigated.

Urinary proteome signature of Renal Cysts and Diabetes syndrome in children.

Renal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in the HNF1B gene encoding for the transcriptional factor hepatocyte nuclear factor-1B. RCAD is characterized as a multi-organ disease, with a broad spectrum of symptoms including kidney abnormalities (renal cysts, renal hypodysplasia, single kidney, horseshoe kidneys, hydronephrosis), early-onset diabetes mellitus, abnormal liver function, pancreatic hypoplasia and genital tract malformations. In the present study, using capillary electrophoresis coupled to mass spectrometry (CE-MS), we investigated the urinary proteome of a pediatric cohort of RCAD patients and different controls to identify peptide biomarkers and obtain further insights into the pathophysiology of this disorder.

Urinary Glycopeptide Analysis for the Investigation of Novel Biomarkers.

Purpose: Urine is a rich source of potential biomarkers, including glycoproteins. Glycoproteomic analysis remains difficult due to the high heterogeneity of glycans. Nevertheless, recent advances in glycoproteomics software solutions facilitate glycopeptide identification and characterization.

Clinical Proteomics in Kidney Disease: From Discovery to Clinical Application.

Proteome analysis has been applied in multiple studies in the context of chronic kidney disease, aiming at improving our knowledge on the molecular pathophysiology of the disease. The approach is generally based on the hypothesis that proteins are key in maintaining kidney function, and disease is a clinical consequence of a significant change of the protein level. Knowledge on critical proteins and their alteration in disease should in turn enable identification of ideal biomarkers that could guide patient management.

Dual mTOR/PI3K inhibition limits PI3K-dependent pathways activated upon mTOR inhibition in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of kidney cysts leading to kidney failure in adulthood. Inhibition of mammalian target of rapamycin (mTOR) slows polycystic kidney disease (PKD) progression in animal models, but randomized controlled trials failed to prove efficacy of mTOR inhibitor treatment. Here, we demonstrate that treatment with mTOR inhibitors result in the removal of negative feedback loops and up-regulates pro-proliferative phosphatidylinositol 3-kinase (PI3K)-Akt and PI3K-extracellular signal-regulated kinase (ERK) signaling in rat and mouse PKD models.

Comparison of Urine and Plasma Peptidome Indicates Selectivity in Renal Peptide Handling.

Purpose: Urine is considered to be produced predominantly as a result of plasma filtration in the kidney. However, the origin of the native peptides present in urine has never been investigated in detail. Therefore, the authors aimed to obtain a first insight into the origin of urinary peptides based on a side-by-side comprehensive analysis of the plasma and urine peptidome.

Proteomics and Metabolomics for AKI Diagnosis.

Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI.

Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?

Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the urinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis.

Urinary peptide biomarker panel associated with an improvement in estimated glomerular filtration rate in chronic kidney disease patients.

Background: An improvement in the glomerular filtration rate (GFR) of chronic kidney disease patients has been an underestimated clinical outcome. Although this may be considered as an unexpected disease course, it may provide some insights into possible mechanisms underlying disease remission and/or regression. Therefore, our aim was to identify urinary peptide biomarkers associated with an improvement in estimated GFR (eGFR) over time and to improve patient stratification.

A Urinary Fragment of Mucin-1 Subunit α Is a Novel Biomarker Associated With Renal Dysfunction in the General Population.

Introduction: Sequencing peptides included in the urinary proteome identifies the parent proteins and may reveal mechanisms underlying the pathophysiology of chronic kidney disease.

Methods: In 805 randomly recruited Flemish individuals (50.8% women; mean age, 51.

Prediction of acute coronary syndromes by urinary proteome analysis.

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.

The use of urinary proteomics in the assessment of suitability of mouse models for ageing.

Ageing 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.

Diastolic Left Ventricular Function in Relation to Urinary and Serum Collagen Biomarkers in a General Population.

Current knowledge on the pathogenesis of diastolic heart failure predominantly rests on case-control studies involving symptomatic patients with preserved ejection fraction and relying on invasive diagnostic procedures including endomyocardial biopsy. Our objective was to gain insight in serum and urinary biomarkers reflecting collagen turnover and associated with asymptomatic diastolic LV dysfunction. We randomly recruited 782 Flemish (51.

Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slowly progressive bilateral renal cyst growth ultimately resulting in loss of kidney function and end-stage renal disease (ESRD). Disease progression rate and age at ESRD are highly variable. Therapeutic interventions therefore require early risk stratification of patients and monitoring of disease progression in response to treatment.

Development of a MALDI MS-based platform for early detection of acute kidney injury.

Purpose: Septic acute kidney injury (AKI) is associated with poor outcome. This can partly be attributed to delayed diagnosis and incomplete understanding of the underlying pathophysiology. Our aim was to develop an early predictive test for AKI based on the analysis of urinary peptide biomarkers by MALDI-MS.