Albuminuria and estimated glomerular filtration rate (eGFR) incompletely predict diabetic kidney disease (DKD) progression. Additional biomarkers may help identify patients at higher risk for renal decline. An analysis presented at the ADA Scientific Sessions 2026 evaluated urinary post-translationally modified Fetuin-A (uPTM-FetA) as a predictor of renal outcomes in participants from the CREDENCE trial with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).

The study analyzed baseline urine samples from 1,466 CREDENCE participants. Associations between uPTM-FetA, urine albumin-to-creatinine ratio (UACR), and eGFR were assessed using Spearman correlation. Cox proportional hazards models evaluated associations between uPTM-FetA and a composite renal outcome. The endpoint included at least 40% decline in eGFR, end-stage kidney disease (ESKD), or renal death. Multivariable analyses adjusted for baseline UACR and eGFR.

Findings

• During a median follow-up of 2.68 years, 112 composite renal events occurred.
• uPTM-FetA showed moderate positive correlation with UACR (ρ=0.46) and inverse correlation with eGFR (ρ=−0.22).
• Higher uPTM-FetA levels were associated with increased risk of renal outcomes (hazard ratio [HR] per log unit 2.02; 95% CI 1.70-2.40; P=2.1×10−15).
• The association remained significant after adjustment for UACR and eGFR (HR 1.25; 95% CI 1.02-1.54; P=0.035).
• Renal risk increased progressively across uPTM-FetA tertiles. HR was 2.36 for tertile 2 versus tertile 1 and 5.80 for tertile 3 versus tertile 1.

This analysis showed that urinary uPTM-FetA was independently associated with renal disease progression in patients with T2DM and CKD. Increasing biomarker levels identified progressively higher renal risk and may improve DKD risk stratification alongside conventional markers.