Urinary angiotensinogen as a novel mortality predictor in diabetic kidney disease: a propensity-matched analysis from the KNOW-CKD.

BACKGROUND

Patients with diabetic kidney disease (DKD) face a substantially higher risk of premature death compared to nondiabetic counterparts, yet accurate biomarkers for stratifying this mortality risk beyond conventional kidney function measures are currently lacking. We investigated whether urinary angiotensinogen (UAGT), reflecting intrarenal renin-angiotensin-aldosterone system activity, predicts all-cause mortality differently among patients with versus without diabetes in chronic kidney disease (CKD).

METHODS

This prospective cohort study included 824 propensity score-matched patients (412 with diabetes and 412 without diabetes) from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease. Participants were categorized into quintiles by baseline urinary angiotensinogen-to-creatinine ratio (UAGT/Cr). Cox proportional hazards models estimated adjusted hazard ratios (HRs) for all-cause mortality.

RESULTS

During median follow-up of 8.9 years, 149 deaths occurred. In patients with diabetes, the highest UAGT/Cr quintile was independently associated with increased mortality compared to the reference quintile (adjusted HR 3.61, 95% confidence interval 1.67-7.81, P < .001) after adjustment for kidney function, proteinuria, and comorbidities. Penalized spline analysis demonstrated a monotonic relationship between UAGT/Cr and mortality in patients with diabetes. In contrast, no significant association was observed in patients without diabetes (P for interaction <.001). Findings remained robust in sensitivity analyses.

CONCLUSION

UAGT/Cr independently predicts all-cause mortality specifically in CKD patients with diabetes but not in those without diabetes, suggesting its potential utility as an etiology-specific prognostic biomarker for risk stratification in DKD.