Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation
Introduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Kidney International Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024923015218 |
| _version_ | 1827595634873466880 |
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| author | Heidrun Rhode Alexandra Lüse Bärbel Tautkus Mary Nabity Ulrike John-Kroegel Friederike Weigel Axel Dost Julia Schitke Oliver Metzing Jan Böckhaus Diana Rubel Wieland Kiess Oliver Gross |
| author_facet | Heidrun Rhode Alexandra Lüse Bärbel Tautkus Mary Nabity Ulrike John-Kroegel Friederike Weigel Axel Dost Julia Schitke Oliver Metzing Jan Böckhaus Diana Rubel Wieland Kiess Oliver Gross |
| author_sort | Heidrun Rhode |
| collection | DOAJ |
| description | Introduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite. Methods: To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls. Results: Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP). Conclusion: We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy. |
| first_indexed | 2024-03-09T02:57:17Z |
| format | Article |
| id | doaj.art-a08aecda0d2b40aea6103198c85d42f7 |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-03-09T02:57:17Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-a08aecda0d2b40aea6103198c85d42f72023-12-05T04:15:35ZengElsevierKidney International Reports2468-02492023-12-0181227782793Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and InflammationHeidrun Rhode0Alexandra Lüse1Bärbel Tautkus2Mary Nabity3Ulrike John-Kroegel4Friederike Weigel5Axel Dost6Julia Schitke7Oliver Metzing8Jan Böckhaus9Diana Rubel10Wieland Kiess11Oliver Gross12Institute of Biochemistry I, Jena University Hospital, Jena, Germany; Correspondence: Heidrun Rhode, Clinics for Internal Medicine I, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany.Institute of Biochemistry I, Jena University Hospital, Jena, GermanyInstitute of Biochemistry I, Jena University Hospital, Jena, GermanyDepartment of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas, USADepartment of Pediatrics, Jena University Hospital, Jena, GermanyDepartment of Pediatrics, Jena University Hospital, Jena, GermanyDepartment of Pediatrics, Jena University Hospital, Jena, GermanyDepartment of Pediatrics, Jena University Hospital, Jena, GermanyDepartment of Pediatrics, Jena University Hospital, Jena, GermanyClinics for Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, GermanyClinics for Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, GermanyHospital for Children and Adolescents, University of Leipzig, Liebigstr. 20a, 04103 Leipzig, GermanyClinics for Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, GermanyIntroduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite. Methods: To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls. Results: Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP). Conclusion: We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy.http://www.sciencedirect.com/science/article/pii/S2468024923015218C4 binding proteincollagen type XIIIdogsearly screeninghyaluronan binding protein 2proteomics |
| spellingShingle | Heidrun Rhode Alexandra Lüse Bärbel Tautkus Mary Nabity Ulrike John-Kroegel Friederike Weigel Axel Dost Julia Schitke Oliver Metzing Jan Böckhaus Diana Rubel Wieland Kiess Oliver Gross Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation Kidney International Reports C4 binding protein collagen type XIII dogs early screening hyaluronan binding protein 2 proteomics |
| title | Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation |
| title_full | Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation |
| title_fullStr | Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation |
| title_full_unstemmed | Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation |
| title_short | Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation |
| title_sort | urinary protein biomarkers reliably indicate very early kidney damage in children with alport syndrome independently of albuminuria and inflammation |
| topic | C4 binding protein collagen type XIII dogs early screening hyaluronan binding protein 2 proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2468024923015218 |
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