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Updated: Jul 8, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently
Heidrun Rhode1, Alexandra Lüse1, Bärbel Tautkus1
1Institute of Biochemistry I, Jena University Hospital, Jena, Germany.
Insights
Early diagnosis of Alport syndrome (AS) is crucial for preemptive therapy. Researchers identified novel urinary protein biomarkers, including collagen type XIII, HABP2, and C4BP, for detecting preclinical kidney injury in AS.
Area of Science:
- Nephrology
- Genetics
- Biomarker Discovery
Background:
- Alport syndrome (AS) is a hereditary kidney disease caused by type IV collagen defects.
- Early diagnosis is essential for preemptive therapy to delay end-stage kidney disease (ESKD).
- Preclinical detection of AS remains a challenge due to the absence of early clinical symptoms.
Purpose of the Study:
- To identify reliable protein biomarkers for the early, preclinical diagnosis of Alport syndrome.
- To enable preemptive therapeutic interventions before significant kidney damage occurs.
Main Methods:
- Mass spectrometry was used to identify candidate protein biomarkers in dogs with preclinical Alport syndrome (stage 0).
- Commercial ELISAs were employed to evaluate candidate biomarkers in urine and blood samples from dogs and children with AS and healthy controls.
- Chromatographic distribution analysis was performed to assess protein variants.
Main Results:
- Urine samples revealed promising biomarkers for early and preclinical kidney injury, unlike blood samples which showed minimal differences.
- Collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP) demonstrated the highest sensitivity and specificity.
- The study identified 74 candidate biomarkers in preclinical canine AS, with subsequent validation in human cohorts.
Conclusions:
- A novel approach combining preclinical canine models and human validation yielded strong candidate biomarkers for Alport syndrome.
- These biomarkers, particularly collagen type XIII, HABP2, and C4BP in urine, show potential for screening and early diagnosis of AS.
- Early detection through these biomarkers can facilitate preemptive therapy, potentially preventing or delaying the progression to end-stage kidney disease.
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.
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