Urinary Markers of Intrarenal Renin-Angiotensin System Activity In Vivo

Abstract

Recent interest focuses on urinary renin and angiotensinogen as markers of renal renin-angiotensin system activity. Before concluding that these components are independent markers, we need to exclude that their presence in urine, like that of albumin (a protein of comparable size), is due to (disturbed) glomerular filtration. This review critically discusses their filtration, reabsorption and local release. Given the close correlation between urinary angiotensinogen and albumin in human studies, it concludes that, in humans, urinary angiotensinogen is a filtration barrier damage marker with the same predictive power as urinary albumin. In contrast, in animals, tubular angiotensinogen release may occur, although tubulus-specific knockout studies do not support a functional role for such angiotensinogen. Urinary renin levels, relative to albumin, are >200-fold higher and unrelated to albumin. This may reflect release of renin from the urinary tract, but could also be attributed to activation of filtered, plasma-derived prorenin and/or incomplete tubular reabsorption.

Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute?

“…However, elevated excretion of angiotensinogen is considered a biomarker for an activated renal RAS in several models of renal injury that reflects the tubular release of angiotensinogen (5,69,72,113). We applied the total angiotensinogen ELISA and immunoblot methods to assess angiotensinogen expression in the salt-sensitive mRen2.Lewis rat, a congenic model of an activated ACE-ANG II-AT 1 R axis, and observed a marked sex difference in urinary angiotensinogen levels (34) (Fig.…”

Methodologic Issues in the Measurement of Urinary Renin

“…Renin-angiotensin system (RAS) components in urine are currently being evaluated as renal disease markers, the underlying concept being that they reflect the activity of the renal RAS independent from the circulating RAS and that the renal RAS contributes to renal disease (1,2). For instance, Alge et al (3) recently suggested that urinary angiotensinogen is a prognostic biomarker for the progression of AKI after cardiac surgery.…”

Urinary angiotensinogen, related factors and clinical implications in normotensive autosomal dominant polycystic kidney disease patients

“…They conclude that source of urinary AGT is plasma not kidneys and urinary AGT level may be a damage marker of glomerular filtration barrier. 17,18 However, in one study, UAGT/UCrea levels in the patients with minimal change disease (8.28 ± 3.70 mg/g) who had severe proteinuria were similar when compared with the control subjects (10.78 ± 3.42 mg/g). 19 Furthermore, the other study which was performed in juvenile type 1 diabetes patients and age-and sex-matched control subjects had important results to support the hypothesis that augmented UAGT levels are not a consequence of proteinuria.…”

“…They found that concentration of urinary renin is 100-to 200-fold higher than urinary AGT. 17,18 It can expect that small variations in UAGT levels may influence the reaction velocity and also amount of generated ANG I in the presence of high renin concentration although there is no available data about the kinetics of AGT-renin reaction in urine. The lots of factors such as urine pH, time of enzyme substrate interaction and compound of urine may change the reaction kinetics.…”