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Coregulation Analysis of Mechanistic Biomarkers in Autosomal Dominant Polycystic Kidney Disease
Johannes Leierer1, Paul Perco1, Benedikt Hofer1
1Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder leading to deterioration of kidney function and end stage kidney disease (ESKD). A number of molecular processes are dysregulated in ADPKD but the exact mechanism of disease progression is not fully understood. We measured protein biomarkers being linked to ADPKD-associated molecular processes via ELISA in urine and serum in a cohort of ADPKD patients as well as age, gender and eGFR matched CKD patients and healthy controls. ANOVA and t-tests were used to determine differences between cohorts. Spearman correlation coefficient analysis was performed to assess coregulation patterns of individual biomarkers and renal function. Urinary epidermal growth factor (EGF) and serum apelin (APLN) levels were significantly downregulated in ADPKD patients. Serum vascular endothelial growth factor alpha (VEGFA) and urinary angiotensinogen (AGT) were significantly upregulated in ADPKD patients as compared with healthy controls. Arginine vasopressin (AVP) was significantly upregulated in ADPKD patients as compared with CKD patients. Serum VEGFA and VIM concentrations were positively correlated and urinary EGF levels were negatively correlated with urinary AGT levels. Urinary EGF and AGT levels were furthermore significantly associated with estimated glomerular filtration rate (eGFR) in ADPKD patients. In summary, altered protein concentrations in body fluids of ADPKD patients were found for the mechanistic markers EGF, APLN, VEGFA, AGT, AVP, and VIM. In particular, the connection between EGF and AGT during progression of ADPKD warrants further investigation.
Insights
Autosomal dominant polycystic kidney disease (ADPKD) involves altered protein biomarkers. Key findings show specific changes in urinary epidermal growth factor (EGF) and angiotensinogen (AGT) linked to kidney function decline in ADPKD patients.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a primary hereditary kidney disease causing kidney function decline and end-stage kidney disease (ESKD).
- The precise molecular mechanisms driving ADPKD progression remain incompletely understood.
- Identifying reliable biomarkers is crucial for understanding and managing ADPKD.
Purpose of the Study:
- To investigate and quantify protein biomarker alterations in body fluids of ADPKD patients.
- To correlate these biomarker changes with kidney function and disease progression.
- To identify potential molecular targets for ADPKD management.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure protein biomarkers in urine and serum.
- ADPKD patient cohorts were compared with age, gender, and eGFR-matched chronic kidney disease (CKD) patients and healthy controls.
- Statistical analyses included ANOVA, t-tests, and Spearman correlation to assess biomarker differences and relationships with renal function.
Main Results:
- Significant alterations in urinary epidermal growth factor (EGF), serum apelin (APLN), serum vascular endothelial growth factor alpha (VEGFA), urinary angiotensinogen (AGT), and arginine vasopressin (AVP) were observed in ADPKD patients.
- Urinary EGF and AGT levels showed a significant negative correlation, and both were associated with estimated glomerular filtration rate (eGFR) in ADPKD patients.
- Serum VEGFA and Vimentin (VIM) concentrations exhibited a positive correlation.
Conclusions:
- Altered levels of EGF, APLN, VEGFA, AGT, AVP, and VIM in body fluids indicate molecular dysregulation in ADPKD.
- The interplay between urinary EGF and AGT is particularly significant and warrants further investigation for its role in ADPKD progression.
- These findings highlight potential novel biomarkers for monitoring ADPKD and its associated kidney function decline.
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