Primary outcome indicator for the progression of acute renal injury: urinary angiotensinogen

Acute renal injury (AKI) is common in patients with acute decompensated heart failure (ADHF). Acute cardiorenal syndrome (CRS), when accompanied by acute cardiovascular and renal dysfunction, is closely associated with mortality and poor prognosis, and may increase the risk of secondary chronic kidney disease (CKD).

Although many patients with acute CRS experience a relatively mild AKI stage (KDIGO or AKIN stage 1, or RIFLE stage R), they generally do not develop to a more severe AKI stage (KDIGO or AKIN stage 2/3, or RIFLE stage F) or dialysis stage, and only about 29% to 48% of patients will develop to a more advanced AKI stage.

Recent studies have shown that mortality increases exponentially with the increase in AKI stage. Early detection of high-risk patients with AKI progression can help doctors formulate plans and initiate appropriate measures to improve renal function, strengthen monitoring of cardiac and renal dysfunction, and implement kidney conservation treatment measures.

Unfortunately, predicting which CRS patients will experience AKI progression or death is a clinical challenge. To address this issue, the research team led by Academician Hou Fanfan of Southern Medical University conducted a prospective, multicenter study to investigate the usefulness of urinary angiotensinogen (uAGT) and other renal injury markers in predicting AKI progression in patients with CRS (AKI stage 1 or 2). The research findings were published in the recent ClinJAm SocNephrol journal.

UAGT has been shown to be an indicator of RAS activation in the kidney. The renin angiotensin system (RAS) in the kidney plays a crucial role in maintaining hemodynamic balance and heart kidney interactions, and it is often destroyed in acute heart failure. In animal experiments, it has been found that intrarenal RAS activation is an initial response to hypoperfusion and an important factor in cardiac and renal injury.

In this prospective, multicenter study, the authors screened 732 hospitalized patients with ADHF, including 213 patients with KDIGO classified as AKI stage 1 or 2, and measured six markers of renal injury, including uAGT, urinary neutrophil gelatinase associated lipid carrier protein (uNGAL), plasma NGAL, urinary interleukin 18 (uIL-18), urinary renal injury molecule-1 (uKIM-1), and urinary albumin to creatinine ratio.

The study used hierarchical deterioration of AKI as the primary outcome indicator for AKI progression, and complication death as a secondary outcome indicator. Through logistic multivariate analysis, after adjusting for multiple confounding factors, it was found that the odds ratios (OR) of the three urine markers for the diagnosis of AKI progression were 10.8 (3.4 to 34.7) for uAGT, 4.7 (1.7 to 13.4) for uNGAL, and 3.6 (1.4 to 9.5) for uIL-18. This indicates that the three markers are significantly correlated with the prognosis of AKI.

Through ROC curve analysis, it was found that uAGT was the best predictor of primary and secondary outcome indicators for AKI progress, with areas under the curve reaching 0.78 and 0.85, respectively. Adding three markers of renal injury in urine to the clinical risk model can significantly improve the risk stratification ability of prognosis.

The authors conclude that detecting uAGT, uNGAL, and uIL-18 can predict the adverse prognosis of AKI. UAGT is the best predictor of this. Adding these renal injury markers to clinical risk models can identify high-risk populations with poor prognosis. The improvement of risk prediction ability can improve the treatment of ADHF, optimize management, and help carry out clinical trials for the treatment of acute CRS.