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Schanstra J.P.,French Institute of Health and Medical Research | Schanstra J.P.,University Paul Sabatier | Mischak H.,Mosaiques Diagnostics and Therapeutics | Mischak H.,University of Glasgow
Pediatric Nephrology

Biomarkers hold the promise of significantly improving health care by enabling prognosis and diagnosis with improved accuracy, and at earlier points in time. Previous results have indicated that single biomarkers are not suitable to describe complex diseases such as kidney disease. Here we provide an update on the progress of urinary proteomics-based studies and strategies to develop biomarker-based classifiers that tolerate instability and inconsistency of individual biomarkers. The examples focus on two major fields in nephrology: chronic kidney disease in the adult population and obstructive nephropathies in the pediatric population. When employed adequately, urinary proteomics demonstrates a clear value in kidney disease, indicating that the current status quo ruling for decades now could be changed by applying modern "omics" approaches. However, while research is able to deliver these useful tools for patient management, the issues associated with implementation are not yet solved. Active engagement of the relevant clinical professional societies, as well as patient's organizations, might help to implement these omics approaches that have shown a clear benefit for the patient. © 2014 IPNA. Source

Klein J.,French Institute of Health and Medical Research | Klein J.,University Paul Sabatier | Bascands J.-L.,French Institute of Health and Medical Research | Bascands J.-L.,University Paul Sabatier | And 4 more authors.
Kidney International

Urinary peptidomics focuses on endogenous urinary peptide content. Many studies now show the usefulness of this approach for the discovery and validation of biomarkers in kidney diseases that are as varied as chronic kidney disease, acute kidney injury, congenital anomalies of the kidney and the urinary tract, and polycystic kidney disease. Most studies focus on chronic kidney disease and demonstrate that urinary peptidome analysis can substantially contribute to early detection and stratification of patients with chronic kidney disease. A number of multicenter studies are ongoing that aim further validation in a clinical setting and broaden the applicability of urinary peptides. The association of urinary peptides with kidney disease also starts to deliver information on the pathophysiology of kidney disease with emphasis on extracellular matrix remodeling. Bioinformatic peptide centric tools have been developed that allow to model the changes in protease activity involved in kidney disease, based on the urinary peptidome content. A novel application of urinary peptidome analysis is the back-translation of results obtained in humans to animals for animal model validation and improvement of readout in these preclinical models. In conclusion, urinary peptidomics not only contribute to detection and stratification of kidney disease in the clinic, but might also create a new impulse in drug discovery through better insight in the pathophysiology of disease and optimized translatability of animal models. © 2016 International Society of Nephrology. Source

Jankowski J.,RWTH Aachen | Schanstra J.P.,French Institute of Health and Medical Research | Schanstra J.P.,University Paul Sabatier | Mischak H.,Mosaiques Diagnostics and Therapeutics | Mischak H.,University of Glasgow
Nephrology Dialysis Transplantation

Body fluid protein-based biomarkers carry the hope of improving patient management in diabetes by enabling more accurate and earlier detection of diabetic kidney disease (DKD), but also of defining the most suitable therapeutic targets. We present the data on some of the best studied individual protein markers in body fluids and conclude that their potential in clinical application for assessing DKD is moderate. Proteome-based approaches aiming at the identification of panels of body fluid biomarkers might be a valid alternative. We discuss the past (first) clinical proteomics studies in DKD, stressing their drawbacks but also the lessons that could be learned from them, as well as the more recent studies that have a potential for actual clinical implementation. We also highlight relevant issues and current problems associated with clinical proteomics from discovery towards application, and give suggestions for solutions that may help guiding proteomic studies, thereby removing some of the current hurdles for implementation of potentially beneficial results. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. Source

Klein J.,Mosaiques Diagnostics and Therapeutics | Buffin-Meyer B.,French Institute of Health and Medical Research | Buffin-Meyer B.,University Paul Sabatier | Mullen W.,University of Glasgow | And 11 more authors.
Expert Review of Proteomics

Clinical proteomics has been applied to the identification of biomarkers of obstetric and neonatal disease. We will discuss a number of encouraging studies that have led to potentially valid biomarkers in the context of Down's syndrome, preterm birth, amniotic infections, preeclampsia, intrauterine growth restriction and obstructive uropathies. Obtaining noninvasive biomarkers (e.g., from the maternal circulation, urine or cervicovaginal fluid) may be more feasible for obstetric diseases than for diseases of the fetus, for which invasive methods are required (e.g., amniotic fluid, fetal urine). However, studies providing validated proteomics-identified biomarkers are limited. Efforts should be made to save well-characterized samples of these invasive body fluids so that many valid biomarkers of pregnancy-related diseases will be identified in the coming years using proteomics based analysis upon adoption of 'clinical proteomics guidelines'. © 2014 Informa UK, Ltd. Source

Bandin F.,French Institute of Health and Medical Research | Bandin F.,Toulouse University Hospital Center | Bandin F.,University Paul Sabatier | Siwy J.,Mosaiques Diagnostics and Therapeutics | And 11 more authors.
Journal of Urology

Purpose: Severe ureteropelvic junction obstruction is treated surgically. However, for milder cases most clinical teams adopt a watchful waiting approach and only operate in the presence of significant decline of renal function combined with severe hydronephrosis. Little is known about the long-term consequences of ureteropelvic junction obstruction. Materials and Methods: Using capillary electrophoresis coupled with mass spectrometry, we analyzed the urinary proteome of 42 patients with ureteropelvic junction obstruction 5 years postoperatively or 5 years following spontaneous resolution. Results: At 5-year followup urinary proteomes were similar between patients with early surgical correction of ureteropelvic junction obstruction and age matched controls. In contrast, urinary proteomes differed significantly between conservatively followed patients and controls. Analyses of the proteomic differences suggested ongoing renal or ureteral remodeling in the conservatively followed patients that was not visible clinically. Conclusions: Long-term followup studies are warranted in patients with ureteropelvic junction obstruction, especially those followed conservatively, to determine whether the observed changes in the urinary proteomes become clinically relevant at a later stage. © 2012 American Urological Association Education and Research, Inc. Source

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