Coregulation Analysis of Mechanistic Biomarkers in Autosomal Dominant Polycystic Kidney Disease

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.