ELISA examining urinary angiotensinogen as a potential indicator of intrarenal renin–angiotensin system (RAS) activity: a clinical study of 128 chronic kidney disease patients

Abstract

In the current study, we measured urinary angiotensinogen (AGT) through enzyme-linked immunoadsordent assay (ELISA) and analyzed its correlation with intrarenal renin-angiotensin system (RAS) activity in 128 chronic kidney disease (CKD) patients. Urinary and plasma renin activity, AGT, angiotensin II (Ang II) and aldosterone levels were also measured by radioimmunoassay (RIA) or ELISA in these participants. Further, the expression level of intrarenal renin, AGT, Ang II and Ang II receptors were examined by immunohistochemistry staining (IHCS) in 72 CKD patients. Their correlations with urinary AGT were also analyzed. We found that the urinary AGT level was positively correlated with hypertension (ρ = 0.28, P < 0.01), urinary protein (r = 0.38, P < 0.01), urinary Ang II (r = 0.29, P < 0.05), urinary type IV collagen (Col IV) (r = 0.56, P < 0.01), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.28, P < 0.01), urinary sodium (r = -0.22, P < 0.05) and serum AGT (r = -0.27, P < 0.01). Multiple regression analysis indicated low serum AGT (P < 0.01), high urinary protein (P < 0.01), high urinary Ang II (P < 0.05) and high urinary Col IV (P < 0.01) were correlated significantly with high urinary AGT. Urinary AGT level was positively correlated with intrarenal expression level of AGT (ρ = 0.46, P < 0.01), Ang II (ρ = 0.56, P < 0.01) and Ang II type 1 receptor (ρ = 0.32, P < 0.01), as detected by IHCS. Together, these data suggest that urinary AGT might be a potential biomarker of intrarenal RAS and Ang II activities in CKD patients.