Angiotensinogen as a biomarker of acute kidney injury

Figures

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  Fig. 1.. Scheme of main RAS pathway: angiotensinogen is cleaved by rennin to form angiotensin I, which is subsequently converted to Ang II by ACE. Ang II binds to Ang II receptors (AT1-R) and (AT2-R). Ang II can also be cleaved by ACE2 to form the vasodilatory and anti-inflammatory peptide angiotensin (1–7) that binds to its specific receptor (Mas-R) to exert its actions. ACE, angiotensin converting enzyme; ACE2, angiotensin-converting enzyme 2; APA, aminopeptidase A; cGMP, cyclic GMP; PGF2, prostaglandin F2; ROS, reactive oxygen species.

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  Fig. 2.. Box and whisker plots showing the distribution of uAnCR (uAGT/creatinine ratio) by group in patients who developed AKI after cardiac surgery. (A) Among patients who had AKI of any AKIN stage at the time of sample collection (n = 97), uAnCR increased in a graded manner with AKI severity (as determined by maximum AKIN stage). (B) uAnCR increased in a graded manner with AKI (urinary Angiotensinogen and creatinine ratio) severity in the subset of patients who were classified as AKIN Stage 1 AKI at the time that their urine samples were collected (n = 79). Box plots show the median (solid line), 25th and 5th percentiles. Error bars represent the 5th and 9th percentiles. AKIN stage groups were compared with the Kruskal–Wallis test (P-value shown in bottom right). The asterisk represents a P < 0.05 compared with AKIN Stage 1 in the post hoc Dunn’s test for pairwise comparison. Figure adapted with permission from Alge et al. [23].

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  Fig. 3.. Angiotensinogen is associated with worsening of AKI. Receiver operator characteristic (ROC) curves were used to test the ability of uAnCR (uAGT/creatinine ratio) to predict worsening of AKI after sample collection among (A) patients who were any stage AKI at the time of collection (n = 97) and (B) the subset who were classified as AKIN Stage 1 at collection (n = 79). Figure adapted with permission from Alge et al. [23].

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  Fig. 4.. Expression of intrarenal RAS associated with uATG level in patients with ATN. (A) uAGT at the time of renal biopsy in patients with ATN and in healthy volunteers. (B) Serum angiotensinogen at the time of renal biopsy in patients with ATN and in healthy volunteers. (C) Correlation between intrarenal angiotensinogen expression and uAGT in patients with ATN. (D) Correlation between intrarenal Ang II expression and uAGT in patients with ATN. t-test, *P < 0.05 versus healthy volunteers in (A) and (B). Pearson correlation, *P < 0.05 in (C) and (D). Figure adapted with permission from Cao et al. [67].

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  Fig. 5.. uAGT level associated with ATN severity. Correlation between uAGT and acute tubular injury score in patient with ATN. Figure adapted with permission from Cao et al. [67].

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  Fig. 6.. ROC analyses for predicting AKI progression or AKI progression with death. (A) The area under the curve (AUC) of renal injury biomarkers [urinary NGAL (uNGAL), urinary IL-18 (uIL-18)] and clinical model, at the time of AKI diagnosis, for predicting AKI progression. (B) The AUCs of renal injury biomarkers (uAGT, uNGAL, uIL-18) and clinical model, at the time of AKI diagnosis, for predicting AKI progression with subsequent death. (C) The performance of combination of renal injury biomarkers for predicting AKI progression. The clinical risk model includes age, gender, hypertension, diabetes, preadmission eGFR, NT-proBNP, serum albumin, hemoglobin, diuretic dosage before AKI, use of spironolactone before AKI, use of RAS inhibitors before AKI and change of serum creatinine from baseline at the time of AKI diagnosis. Figure adapted with permission from Chen et al. [81].