Association of plasma angiogenin with risk of incident end-stage kidney disease in individuals with type 2 diabetes

We aim to investigate the association between plasma angiogenin and the risk of progression to end-stage kidney disease (ESKD) in Type 2 Diabetes (T2D) patients and attempted to infer the causal relationship between plasma angiogenin and chronic kidney disease. A total of 1863 outpatients with T2D were included in this prospective cohort study. ESKD was defined as a composite of progression to sustained eGFR below 15 ml/min/1.73m², maintenance dialysis or death due to renal causes. The secondary outcome was rapid kidney function decline defined as eGFR decline of 5 ml/min/1.73m² or greater per year. Over a median follow-up of 9.3 years, 125 incident ESKD events were identified. Elevated plasma angiogenin levels were associated with an increased risk of incident ESKD (adjusted HR 1.25, 95% CI 1.01-1.55, per one SD) independent of cardio-renal risk factors including baseline eGFR and albuminuria. A high level of plasma angiogenin was also associated with an increased risk for rapid kidney function decline (adjusted OR 1.31 [1.07-1.61] per 1-SD). A two-sample Mendelian randomization approach suggested a potential causal relationship between plasma angiogenin and chronic kidney disease. Plasma angiogenin may be a novel biomarker and potential therapeutic target for progressive kidney disease in patients with T2D.