A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease
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...
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MDPI AG
2021-07-01
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| Series: | Proteomes |
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| Online Access: | https://www.mdpi.com/2227-7382/9/3/32 |
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| author | Lorenzo Catanese Justyna Siwy Emmanouil Mavrogeorgis Kerstin Amann Harald Mischak Joachim Beige Harald Rupprecht |
| author_facet | Lorenzo Catanese Justyna Siwy Emmanouil Mavrogeorgis Kerstin Amann Harald Mischak Joachim Beige Harald Rupprecht |
| author_sort | Lorenzo Catanese |
| collection | DOAJ |
| description | 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 (<i>n</i> = 200) and a test (<i>n</i> = 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 (<i>n</i> = 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, <i>p</i> < 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. |
| first_indexed | 2024-03-10T07:16:04Z |
| format | Article |
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| issn | 2227-7382 |
| language | English |
| last_indexed | 2024-03-10T07:16:04Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Proteomes |
| spelling | doaj.art-0db711690ca7460ca66977e85b06f2c62023-11-22T15:01:07ZengMDPI AGProteomes2227-73822021-07-01933210.3390/proteomes9030032A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney DiseaseLorenzo Catanese0Justyna Siwy1Emmanouil Mavrogeorgis2Kerstin Amann3Harald Mischak4Joachim Beige5Harald Rupprecht6Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, 95447 Bayreuth, GermanyMosaiques Diagnostics GmbH, 30659 Hannover, GermanyMosaiques Diagnostics GmbH, 30659 Hannover, GermanyDepartment of Nephropathology, Institute of Pathology, University of Erlangen-Nürnberg, 91054 Erlangen, GermanyMosaiques Diagnostics GmbH, 30659 Hannover, GermanyDepartment of Infectious Diseases/Tropical Medicine, Nephrology/KfH Renal Unit and Rheumatology, St. Georg Hospital Leipzig, 04129 Leipzig, GermanyDepartment of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, 95447 Bayreuth, GermanyNon-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 (<i>n</i> = 200) and a test (<i>n</i> = 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 (<i>n</i> = 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, <i>p</i> < 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.https://www.mdpi.com/2227-7382/9/3/32fibrosisurinepeptidesIFTAbiomarkers |
| spellingShingle | Lorenzo Catanese Justyna Siwy Emmanouil Mavrogeorgis Kerstin Amann Harald Mischak Joachim Beige Harald Rupprecht A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease Proteomes fibrosis urine peptides IFTA biomarkers |
| title | A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease |
| title_full | A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease |
| title_fullStr | A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease |
| title_full_unstemmed | A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease |
| title_short | A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease |
| title_sort | novel urinary proteomics classifier for non invasive evaluation of interstitial fibrosis and tubular atrophy in chronic kidney disease |
| topic | fibrosis urine peptides IFTA biomarkers |
| url | https://www.mdpi.com/2227-7382/9/3/32 |
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