Elevated urinary angiotensinogen excretion links incidence of chronic kidney disease among community-dwelling population: The Aging Kidney Study

OBJECTIVES: Activation of the intrarenal renin-angiotensin system (RAS) has been implicated in chronic kidney disease (CKD) pathophysiology. Although urinary angiotensinogen (AGT) is a noninvasive surrogate marker of intrarenal RAS activity, whether urinary AGT is associated with incident CKD remains unclear. We investigated the association between urinary AGT and incident CKD in community-dwelling adults without CKD. METHODS: We conducted a prospective cohort study of community-dwelling adults without CKD. Urinary AGT, urinary N-acetyl-β-d-glucosaminidase (NAG), urinary β2-microglobulin (β2-MG), urinary albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) were assessed at baseline. Incident CKD was defined according to established criteria based on eGFR and urinary ACR during follow-up. Associations between urinary AGT levels and incident CKD were examined using multivariable-adjusted Cox proportional hazards models. RESULTS: Among 197 participants without CKD at baseline, 22% developed incident CKD during a median follow-up of 4.9 years. Weak to moderate correlations were observed between urinary AGT levels and kidney-related markers at baseline, including an inverse correlation with eGFR (ρ = -0.21) and positive correlations with urinary ACR (ρ = 0.44), urinary NAG (ρ = 0.35), and urinary β2-MG (ρ = 0.56). Higher baseline urinary AGT levels were significantly associated with an increased risk of incident CKD [adjusted hazard ratio per 1-SD increase, 1.48; 95% confidence interval (CI), 1.02-2.16] after multivariable adjustment. CONCLUSION: Higher urinary AGT levels were associated with incident CKD in individuals with preserved kidney function, suggesting that urinary AGT may serve as a marker of early CKD risk.