Urinary Angiotensinogen as a Potential Biomarker of Intrarenal Renin-angiotensin System Activity in Chinese Patients with Chronic Kidney Disease.

Abstract

Urinary angiotensinogen (AGT) mainly derives from the AGT produced in the proximal tubular cells. Evidence exists that supports the correlation between urinary AGT and circulating AGT. Previous studies measured urinary AGT by radioimmunoassay which is not convenient for clinical practice. In this study, we utilized an enzyme-linked immunosorbent assay (ELISA) based method to quantify urinary AGT. We analysed the relationship between urinary AGT and intrarenal angiotensin II (Ang II) activity in patients with chronic kidney disease (CKD). Urinary and plasma renin activity, AGT, Ang II and aldosterone were measured by radioimmunoassay or ELISA in 128 CKD patients. Furthermore, expression levels of intrarenal renin, AGT, Ang II and Ang II receptor were examined by immunohistochemistry staining (IHCS) in 72 CKD patients undergoing renal biopsy. Average urinary AGT was 2.02 ± 0.55 ng/(mg Cr). Hypertension, urinary protein, urinary Ang II and urinary Type IV collagen (Col IV) positively correlated with urinary AGT. Estimated glomerular filtration rate (eGFR), urinary sodium and serum AGT negatively correlated with urinary AGT. Multiple regression analysis indicated that low serum AGT, high urinary protein, urinary Ang II and urinary Col IV correlated significantly with high urinary AGT. Moreover, we observed positive correlation between urinary AGT and positive IHCS area of AGT, Ang II and Ang II Type 1 receptor inrenal tissue. These data suggest that urinary AGT might be a potential biomarker of intrarenal angiotensin II activity in CKD patients.