Angiotensinogen as a biomarker of acute kidney injury

Abstract

Early recognition of acute kidney injury (AKI) is critical to prevent its associated complications as well as its progression to long term adverse outcomes like chronic kidney disease. A growing body of evidence from both laboratory and clinical studies suggests that inflammation is a key factor contributing to the progression of AKI regardless of the initiating event. Biomarkers of inflammation are therefore of interest in the evaluation of AKI pathogenesis and prognosis. There is evidence that the renin angiotensin aldosterone system is activated in AKI, which leads to an increase in angiotensin II (Ang II) formation within the kidney. Ang II activates pro-inflammatory and pro-fibrotic pathways that likely contribute to the progression of AKI. Angiotensinogen is the parent polypeptide from which angiotensin peptides are formed and its stability in urine makes it a more convenient marker of renin angiotensin system activity than direct measurement of Ang II in urine specimens, which would provide more direct information. The potential utility of urinary angiotensinogen as a biomarker of AKI is discussed in light of emerging data showing a strong predictive value of AKI progression, particularly in the setting of decompensated heart failure. The prognostic significance of urinary angiotensinogen as an AKI biomarker strongly suggests a role for renin–angiotensin system activation in modulating the severity of AKI and its outcomes.

Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System

“…The pathogenesis of AKI is complex, often involving hemodynamic and non-hemodynamic mechanisms [41][42][43][44]. Alterations in the RAS have been shown to contribute to the development of AKI and are associated with adverse outcomes both in experimental and clinical studies [45][46][47][48][49][50]. Several components of the kidney RAS, such as urine Angiotensinogen and Ang II, the main active peptide, are increased in experimental AKI caused by ischemia-reperfusion AKI [45][46][47][51][52][53][54][55][56] ACE inhibitors (ACEi) and angiotensin receptor antagonists (ARBs) may attenuate renal inflammation, injury and improve renal function in the ischemia-reperfusion model of AKI [57][58][59][60].…”

Nomogram Model to Predict Cardiorenal Syndrome Type 1 in Patients with Acute Heart Failure

“…AGT, a principal substrate of the local intrarenal renin-angiotensin system (RAS), is mainly formed in the proximal tubule cells and secreted into the tubule lumen [32,33]. Increasing evidence has suggested the strong predictive role of uAGT in the initiation and progression of AKI, particularly in the setting of heart failure.…”

Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus

“…RAS blockers are known to reduce the levels of urinary and kidney AOG by suppressing angiotensin II (Ang II), a positive regulator of AOG (Kobori et al, ; Ba Aqeel et al, ). Of note, elevated uAOG was found despite the fact that RAS blockers were used far more frequently in cases than in the controls during EDIC (Table ).…”

“…By extrapolation, RAS blockade would seem more effective when such RAS overactivity can be documented by a relatively easy measurement of a key RAS component of this system such as urinary AOG. RAS blockers are known to reduce the levels of urinary and kidney AOG by suppressing angiotensin II (Ang II), a positive regulator of AOG (Kobori et al, 1979;Ba Aqeel et al, 2017). Of note, elevated uAOG was found despite the fact that RAS blockers were used far more frequently in cases than in the controls during EDIC (Table 1).…”