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Rhode, Heidrun; Lüse, Alexandra; Tautkus, Bärbel; Nabity, Mary; John-Kroegel, Ulrike; Weigel, Friederike; Dost, Axel; Schitke, Julia; Metzing, Oliver; Boeckhaus, Jan; Rubel, Diana; Kiess, Wieland; Gross, Oliver
Kidney international reports, 12/2023, Letnik: 8, Številka: 12Journal Article
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 (ESKD) early in life. The earlier therapy starts, the more effectively ESKD can be delayed. Clearly then, to ensure pre-emptive therapy, early diagnosis is an essential prerequisite. To provide such early diagnosis, we searched for protein biomarkers by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate biomarkers. Of these, using commercial ELISAs, we evaluated 27 in dogs and 28 in children, fifty with AS and one hundred and four healthy controls. Most biomarkers 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 the disease-specific variants. In urine, however, several proteins individually, or in combination, were promising indicators of very early and pre-clinical kidney injury. The biomarkers with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2, and complement C4 binding protein. We generated very strong candidate biomarkers by our approach of first examining pre-clinical AS in dogs and then validating these biomarkers in children at early stages of disease. These biomarkers might serve for screening purposes for AS before the onset of kidney damage and so allow pre-emptive therapy. Display omitted
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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