Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 6 (2), 108-116

Urinary Angiotensinogen as a Novel Biomarker of Intrarenal Renin-Angiotensin System in Chronic Kidney Disease

Affiliations

Urinary Angiotensinogen as a Novel Biomarker of Intrarenal Renin-Angiotensin System in Chronic Kidney Disease

Hiroyuki Kobori et al. Int Rev Thromb.

Abstract

An activated intrarenal reninangiotensin system (RAS) plays a crucial role in the pathogenesis of hypertension and chronic kidney diseases (CKD). Angiotensinogen (AGT) is the only known substrate for renin, which is the rate-limiting enzyme of the RAS. Because the levels of AGT are close to the Michaelis-Menten constant for renin, AGT levels can also control the RAS activity, and upregulation of AGT may lead to elevated angiotensin peptide levels and increases in blood pressure. Recent studies on experimental animal models have documented the involvement of AGT in the intrarenal RAS activation and development of hypertension. Enhanced intrarenal AGT mRNA and/or protein levels occur in experimental models of hypertension and kidney diseases supporting important roles in the development and progression of hypertension and kidney diseases. Urinary excretion rates of AGT provide a specific index of intrarenal RAS status in angiotensin II-infused rats. Also, a direct quantitative method was recently developed to measure urinary AGT using human AGT ELISA. These data prompted us to measure urinary AGT in patients with hypertension and CKD, and investigate correlations with clinical parameters. This brief review will address the potential of urinary AGT as a novel biomarker of the intrarenal RAS status in hypertension and CKD.

Figures

Figure 1
Figure 1
Figure 1A. Intrarenal renin-angiotensin (Ang) system (RAS) in proximal and distal nephron segments . Because of its molecular size, it seems unlikely that much of the plasma angiotensinogen (AGT) filters across the glomerular membrane. In Ang II-dependent hypertension, increased proximal tubular (PT) secretion of AGT spills over into the distal nephron and increases Ang II effects on distal tubular (DT) reabsorption. CD, collecting ducts. ACE, Ang converting enzyme. AT1, Ang II type 1 receptors. Figures 1B – 1D. Urinary protein and AGT excretion rates of each group . B. Urinary excretion rates of total protein were greater in Ang II-infused animals. ARB treatment prevented this augmentation. C. Representative western blot analysis of urinary AGT levels among groups showing the stimulation in Ang II-infused group. D. Urinary excretion rates of AGT were increased by 4.7-times in Ang II-infused animals. ARB treatment prevented this augmentation. ARB, AT1 blocker. DU, densitometric units. *, p < 0.05 compared to the sham group.
Figure 2
Figure 2
Figure 2A. UAGT/UCre levels were significantly increased in hypertensive patients not treated with RAS blockers (RASB) compared with normotensive subjects . Patients treated with RAS blockers exhibited a marked attenuation of this augmentation. *, p < 0.05 vs. Normotensive. †, p < 0.05 vs. HTN - RASB. Figure 2B. Log(UAGT/UCre) levels in chronic kidney disease (CKD) patients and in healthy volunteers . Log(UAGT/UCre) levels were significantly increased in CKD patients compared with that in control subjects.
Figure 3
Figure 3
Figure 3A. UAGT/UCre levels in chronic glomerulonephritis patients (CGN) with/without renin-angiotensin system blockade (RASB) and in control subjects . *, P < 0.05 vs. Control subjects. †, P < 0.05 vs. CGN - RASB. Figures 3B – 3E. Intrarenal Ang II and urinary AGT in patients with IgA nephropathy . B. Urinary AGT levels were significantly suppressed by ARB treatments. C–E. Representative images of immunostaining of Ang II in renal tissues from biopsy samples in patients with minor glomerular abnormality (MGA, C) and IgA nephropathy (D–E) are shown. In the patient with IgA nephropathy, renal biopsy samples were also collected after treatment with an ARB, and Ang II immunostaining was determined. Each pair of the panels D and E comes from one IgA nephropathy patient (pretreatment; D vs. post treatment; E). Immunoreactivity of Ang II in tubules appeared to be higher in patients with IgA nephropathy than in patients with MGA. Furthermore, treatment with ARB decreased immunoreactivity of Ang II in tubules from patients with IgA nephropathy.

Similar articles

See all similar articles

Cited by 13 articles

See all "Cited by" articles

LinkOut - more resources

Feedback