Introduction and Objective: Albuminuria incompletely predicts diabetic kidney disease (DKD) progression. Urinary post-translationally modified Fetuin-A (uPTM-FetA) reflects kidney stress-related pathophysiology. We evaluated whether uPTM-FetA predicts renal outcomes independent of albuminuria and eGFR in CREDENCE participants with type 2 diabetes and CKD.Methods: Baseline urine from 1,466 participants was analyzed for uPTM-FetA. Associations with UACR and eGFR were assessed using Spearman correlation. Cox models evaluated risk of the renal composite (≥40% eGFR decline, ESKD, or renal death). Multivariable models adjusted for UACR and eGFR.Results: Over median 2.68 years, 112 renal events occurred. uPTM-FetA correlated with UACR (ρ=0.46) and inversely with eGFR (ρ=−0.22). Higher uPTM-FetA predicted renal outcomes (HR per log unit 2.02 [1.70-2.40], p=2.1×10−15) and remained significant after adjustment (HR 1.25 [1.02-1.54], p=0.035). Risk increased across tertiles (HR T2 vs T1 2.36; HR T3 vs T1 5.80).Conclusion: uPTM-FetA predicts renal disease progression independent of albuminuria and eGFR in type 2 diabetes with CKD. Increasing levels identify progressively higher renal risk, supporting uPTM-FetA as a biomarker for improved DKD risk stratification.
T.K. Tseng: Board Member; Current; Bio Preventive Medicine Corp. E. Button: None. C. Rossi: None. F. Raggi: None. A. Solini: None. C. Huang: Employee; Current; Bio Preventive Medicine Corp. E. Ferrannini: Research Support; Current; Precsion Diabetes, Inc. Consultant; Ended; 23andMe, Inc.
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