Does urinalysis angiotensinogen (uAGT) predict acute kidney injury (AKI) in patients with heart failure?

Urinary Angiotensinogen Predicts Acute Kidney Injury in Heart Failure

Urinary angiotensinogen (uAGT) is an effective biomarker for predicting acute kidney injury (AKI) progression in patients with heart failure, with superior predictive value compared to other renal injury biomarkers. 1, 2

Understanding AKI in Heart Failure

Acute kidney injury in heart failure represents a significant clinical challenge, often manifesting as cardio-renal syndrome (CRS). There are specific types of CRS relevant to this question:

• Type 1: Acute heart failure causing acute kidney injury
• Type 2: Chronic heart failure causing chronic kidney disease 3

Heart failure patients are particularly susceptible to AKI due to:

1. Reduced cardiac output decreasing renal perfusion
2. Increased central venous pressure affecting renal function
3. Neurohormonal activation, particularly of the renin-angiotensin-aldosterone system
4. Medications used to treat heart failure (diuretics, ACE inhibitors, ARBs) 3

Evidence for uAGT as a Predictor of AKI

The most recent and highest quality evidence strongly supports uAGT as a predictor of AKI in heart failure:

• In a 2025 prospective multicenter study, elevated baseline uAGT levels were associated with "ongoing AKI" in patients with acute decompensated heart failure (ADHF) 1
• Patients with ongoing AKI had significantly higher mortality (HR 6.89) and worse cardiorenal outcomes 1
• A 2016 study found uAGT was the best predictor of AKI progression among six biomarkers tested, with an area under the receiver operating curve of 0.78 2
• After multivariable adjustment, the highest tertile of uAGT was associated with 10.8 times higher odds of AKI progression compared to the lowest tertile 2

Comparison with Other Biomarkers

When compared to other renal injury biomarkers, uAGT demonstrates superior predictive performance:

• uAGT outperformed urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary IL-18 (uIL-18) in predicting AKI progression 2
• uAGT provided the best risk reclassification improvement compared to clinical models alone (category-free net reclassification improvement of 0.76) 2
• In contrast, traditional tubular injury biomarkers were not strongly associated with outcomes in heart failure patients experiencing worsening renal function 4

Clinical Application

For optimal use of uAGT in predicting AKI in heart failure patients:

1. Measure uAGT at the time of heart failure diagnosis or admission
2. Higher uAGT levels indicate increased risk for AKI progression
3. Pay particular attention to patients with:
   • Chronic kidney disease
   • Use of beta-blockers and thiazide diuretics
   • Lack of renin-angiotensin system blocker prescription 1

Potential Pitfalls and Caveats

• The relationship between uAGT and AKI may be affected by medication use, particularly RAS blockers 1
• AKI definitions vary across studies, with the Kidney Disease Improving Global Outcomes (KDIGO) criteria being the most current standard 3
• Distinguishing between new-onset AKI and acute-on-chronic kidney injury (ACKI) is important, as ACKI carries worse prognosis 5
• Current guidelines recommend traditional markers (serum creatinine and urine output) for AKI diagnosis, but these have limitations in early detection 3

Conclusion

The evidence clearly demonstrates that uAGT is a valuable biomarker for predicting AKI in heart failure patients, offering superior prognostic information compared to conventional markers and other novel biomarkers. Its use can help identify patients at highest risk for adverse outcomes, potentially enabling earlier intervention.