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Article

A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease

1
Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, 95447 Bayreuth, Germany
2
Kuratorium for Dialysis and Transplantation (KfH) Bayreuth, 95445 Bayreuth, Germany
3
Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany
4
Mosaiques Diagnostics GmbH, 30659 Hannover, Germany
5
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital, 52074 Aachen, Germany
6
Department of Nephropathology, Institute of Pathology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
7
Department of Infectious Diseases/Tropical Medicine, Nephrology/KfH Renal Unit and Rheumatology, St. Georg Hospital Leipzig, 04129 Leipzig, Germany
8
Kuratorium for Dialysis and Transplantation (KfH) Renal Unit, Hospital St. Georg, 04129 Leipzig, Germany
9
Department of Internal Medicine II, Martin-Luther-University Halle/Wittenberg, 06108 Halle (Saale), Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Uma K. Aryal
Proteomes 2021, 9(3), 32; https://doi.org/10.3390/proteomes9030032
Received: 2 June 2021 / Revised: 6 July 2021 / Accepted: 7 July 2021 / Published: 13 July 2021
(This article belongs to the Special Issue Mass Spectrometry-Based Quantitative Proteomics)
Non-invasive urinary peptide biomarkers are able to detect and predict chronic kidney disease (CKD). Moreover, specific urinary peptides enable discrimination of different CKD etiologies and offer an interesting alternative to invasive kidney biopsy, which cannot always be performed. The aim of this study was to define a urinary peptide classifier using mass spectrometry technology to predict the degree of renal interstitial fibrosis and tubular atrophy (IFTA) in CKD patients. The urinary peptide profiles of 435 patients enrolled in this study were analyzed using capillary electrophoresis coupled with mass spectrometry (CE-MS). Urine samples were collected on the day of the diagnostic kidney biopsy. The proteomics data were divided into a training (n = 200) and a test (n = 235) cohort. The fibrosis group was defined as IFTA ≥ 15% and no fibrosis as IFTA < 10%. Statistical comparison of the mass spectrometry data enabled identification of 29 urinary peptides with differential occurrence in samples with and without fibrosis. Several collagen fragments and peptide fragments of fetuin-A and others were combined into a peptidomic classifier. The classifier separated fibrosis from non-fibrosis patients in an independent test set (n = 186) with area under the curve (AUC) of 0.84 (95% CI: 0.779 to 0.889). A significant correlation of IFTA and FPP_BH29 scores could be observed Rho = 0.5, p < 0.0001. We identified a peptidomic classifier for renal fibrosis containing 29 peptide fragments corresponding to 13 different proteins. Urinary proteomics analysis can serve as a non-invasive tool to evaluate the degree of renal fibrosis, in contrast to kidney biopsy, which allows repeated measurements during the disease course. View Full-Text
Keywords: fibrosis; urine; peptides; IFTA; biomarkers fibrosis; urine; peptides; IFTA; biomarkers
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MDPI and ACS Style

Catanese, L.; Siwy, J.; Mavrogeorgis, E.; Amann, K.; Mischak, H.; Beige, J.; Rupprecht, H. A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease. Proteomes 2021, 9, 32. https://doi.org/10.3390/proteomes9030032

AMA Style

Catanese L, Siwy J, Mavrogeorgis E, Amann K, Mischak H, Beige J, Rupprecht H. A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease. Proteomes. 2021; 9(3):32. https://doi.org/10.3390/proteomes9030032

Chicago/Turabian Style

Catanese, Lorenzo, Justyna Siwy, Emmanouil Mavrogeorgis, Kerstin Amann, Harald Mischak, Joachim Beige, and Harald Rupprecht. 2021. "A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease" Proteomes 9, no. 3: 32. https://doi.org/10.3390/proteomes9030032

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