Changes in urinary angiotensinogen posttreatment in pediatric IgA nephropathy patients

Abstract

Background: Recently, we demonstrated that urinary angiotensinogen (AGT) levels are increased and reflect intrarenal renin-angiotensin system (RAS) status in pediatric patients with chronic glomerulonephritis. Therefore, this study was performed to test the hypothesis that urinary AGT (UAGT) levels provide a specific index of intrarenal RAS status associated with RAS blockade treatment in pediatric IgA nephropathy (IgAN) patients.

Methods: We measured plasma and UAGT levels and urinary transforming growth factor beta (TGF-β) levels, after which we performed immunohistochemical analysis of AGT, angiotensin II (Ang II), and TGF-β in 24 pediatric IgAN patients treated with RAS blockades for 2 years. Paired tests were used to analyze the changes from baseline to study end.

Results: Although there was no change in plasma AGT levels, UAGT and TGF-β levels were significantly decreased after RAS blockade, which was accompanied by the expression levels of AGT, Ang II, and TGF-β, as well as the magnitude of glomerular injury. Baseline UAGT levels positively correlated with diastolic blood pressure, urinary protein levels, scores for mesangial hypercellularity, and the expression levels of AGT, Ang II, and TGF-β in renal tissues.

Conclusions: These data indicate that UAGT is a useful biomarker of intrarenal RAS activation, which is associated with glomerular injury during RAS blockade in pediatric IgAN patients.

Fig. 1

Changes in plasma angiotensinogen (AGT) in pediatric patients with immunoglobulin A nephropathy (IgAN) after renin–angiotensin system (RAS) blockade (a). Changes in logarithmically transformed urinary AGT/urinary creatinine ratio (Log[UAGT/UCre]) in pediatric patients with IgAN after RAS blockade (b). Changes in logarithmically transformed urinary transforming growth factor beta (TGF-β)/creatinine ratio (Log[UTGF-β/UCre]) in pediatric patients with IgAN after RAS blockade (c). Each marker and line represents an individual participant in the study

Fig. 2

Representative images of angiotensinogen (AGT) (a, b), angiotensin II (Ang II) (c, d), and transforming growth factor beta (TGF-β) (e, f) in pediatric patients with immunoglobulin A nephropathy (IgAN) at baseline (a, c, e) vs. posttreatment (b, d, f). Renin–angiotensin system (RAS) blockade decreased immunoreactivity of AGT, Ang II, and TGF-β in renal tissues from pediatric patients with IgAN

Fig. 3

Multiple regression analysis for logarithmically transformed urinary angiotensinogen (AGT)/urinary creatinine ratio (Log[UAGT/UCre]) in pediatric immunoglobulin A nephropathy (IgAN) patients. Only two parameters—angeotensin II (Ang II) expression levels by immunohistochemical study and urinary protein/UCre ratio [UPro/UCre])—accounted for 76.88 % of the variation in the Log(UAGT/UCre) (r=0.8768, R²=0.7688, P<0.0001)