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. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in Masson trichrome stained kidney tissues. The urinary proteome was analysed by capillary electrophoresis coupled to mass spectrometry. CKD273 displayed a significant and positive correlation with the degree of fibrosis (Rho = 0.430, P = 0.0044), while the routinely used parameters (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio) did not (Rho = -0.222; -0.137; -0.070 and P = 0.16; 0.39; 0.66, respectively). We identified seven fibrosis-associated peptides displaying a significant and negative correlation with the degree of fibrosis. All peptides were collagen fragments, suggesting that these may be causally related to the observed accumulation of ECM in the kidneys. CKD273 and specific peptides are significantly associated with kidney fibrosis; such an association could not be detected by other biomarkers for CKD. These non-invasive fibrosis-related biomarkers can potentially be implemented in future trials.

1st Department of Medicine 3rd Faculty of Medicine Charles University Prague Czech Republic

Biotechnology Division Biomedical Research Foundation Academy of Athens Athens Greece

Clinic of Nephrology Clinical Center of Serbia Belgrade Serbia

Department of Nephrology 'Victor Babes' University of Medicine and Pharmacy County Emergency Hospital Timisoara Romania

Department of Nephrology and Transplantation Medicine Wroclaw Medical University Wroclaw Poland

Department of Nephrology Medical Faculty University of Skopje Skopje Macedonia

Department of Nephrology University Hospital Center Mother Teresa Tirana Albania

Department of Nephrology University of Campania Luigi Vanvitelli Naples Italy

Department of Pediatric Nephrology Hannover Medical School Hannover Germany

IIS Fundacion Jimenez Diaz UAM Madrid Spain

Institut National de la Santé et de la Recherche Médicale Institute of Cardiovascular and Metabolic Disease Toulouse France

Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow UK

Macedonian Academy of Sciences and Arts Skopje Macedonia

Mosaiques Diagnostics GmbH Hannover Germany

Nephropathology Center San Gerardo Hospital Monza Italy

School of Medicine University of Belgrade Belgrade Serbia

Université Toulouse 3 Paul Sabatier Toulouse France

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