Year: 2026
Type: article
Abstract: Introduction: Early diagnosis of Alport syndrome (AS) in children remains challenging because early manifestations are nonspecific. Some clinically suspected cases remain genetically unresolved because no disease-causing variant has been identified or the variants identified are of uncertain significance. Urinary peptidomics is a promising noninvasive biomarker approach. We aimed to develop and validate a urinary peptidomic signature for pediatric AS. Methods: ) enrolled in EARLY PRO-TECT trial, along with 651 samples from pediatric kidney disease cohorts and healthy controls. The data set was randomly divided into discovery (70%) and validation (30%) cohorts. Differential peptides identified by Wilcoxon testing with Benjamini-Hochberg adjustment were used to develop a support vector machine classifier. Performance was assessed by cross-validation and application to the validation cohort. Results: A total of 151 discriminatory peptides were identified. Sequence information was available for 87 peptides used for classifier generation; 60.9% were collagen-derived. In validation, the classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.999 (95% confidence interval [CI], 0.997-1.000), with 100% sensitivity, 97.4% specificity, and 98.2% accuracy. After adjustment for age, sex, and eGFR, performance remained high (adjusted AUC, 0.918 [95% CI, 0.884-0.951]). Longitudinal analyses demonstrated stable classifier scores over up to 3 years. Conclusion: We developed and validated an accurate urinary peptidomic classifier for noninvasive diagnosis of pediatric AS. The signature may complement genetic testing and support earlier recognition of AS.
Source: Kidney International Reports
Authors: Julia Byrska, Jan Boeckhaus, Kleanthi Voutsadaki, Benjamin Breuil, Eléonore Delecroix, Sheila Murunga, Bénédicte Buffin-Meyer, Brian Becknell, Daryl McLeod, Kathrin Burgmaier, Max C. Liebau, Franz Schaefer, Justyna Siwy, Harald Mischak, Margarita Kondyli, Stéphane Decramer, Maria D. Sanchez-Niño, Alberto Ortiz, Oliver Gross, Joost P. Schanstra
Institutions: Hospital Universitario Fundación Jiménez Díaz, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Universitätsmedizin Göttingen, Inserm, Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, Heidelberg University, Nationwide Children's Hospital, Abigail Wexner Research Institute, University of Cologne, University Hospital Cologne, Deggendorf Institute of Technology, Universitätsklinikum Aachen, RWTH Aachen University, Mosaiques Diagnostics and Therapeutics (Germany), Centre Hospitalier Universitaire de Toulouse
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
Funders: Children's Hospital of Philadelphia, Comunidad de Madrid, European Commission, Bundesministerium für Bildung und Forschung, Universität zu Köln, European Renal Association-European Dialysis and Transplant Association, European Rare Kidney Disease Reference Network, National Institutes of Health, HORIZON EUROPE Framework Programme, Research Executive Agency, Instituto de Salud Carlos III, European Regional Development Fund, National Institute of Diabetes and Digestive and Kidney Diseases, H2020 Marie Skłodowska-Curie Actions, European Health and Digital Executive Agency
Awards: G1011636513, G1259844765, G1267673959, Promoviendo las defensas endógenas frente a la enfermedad renal, NEOCYST - Netzwerk für frühe zystische Nierenerkrankungen: Koordination und Register, Prognosemodelle, Zilien-Biologie, G2373695302, G2525722903, G2650182398, Multi-markers risk assessment of kidney sensitivity to injury to personalize prevention of acute kidney injury, Therapies for Renal Ciliopathies, G4290602301, Novel roles for urothelium during urinary tract obstruction, NEOCYST - Netzwerk für frühe zystische Nierenerkrankungen: Entwicklung von Erhebungsinstrumenten für patientenrelevante Endpunkte, Nierenorganoide und Wirkstoffscreening, NEOCYST - Netzwerk für frühe zystische Nierenerkrankungen: Register, Pathophysiologie von Ziliopathien und Datenintegration, G511460989, G6604067511, G686850710, Conservando la expresión de Klotho para retrasar el envejecimiento renal, Nuevos abordajes diagnósticos y terapéuticos para prevenir la muerte celular e inflamación activados por RIPK1 y RIPK3 en el fracaso renal agudo, G7797547491, G8160529855, G8185718001, Developing a framework/model to environmentally sustainable and climate neutral health and care systems using the Kidney care pathway, G8529818865, G8536619142, CHOP Pediatric Center of Excellence in Nephrology, Spain CKD cause (SPACKDc), G998287453
OpenAlex ID: W7214283502