VICM, a Biomarker of Macrophage-Driven Inflammation, as a Risk Marker of Diabetic Kidney Disease Progression in People with Type 2 Diabetes and Microalbuminuria

Introduction and Objective: Hyperglycemia-induced metabolic stress promotes macrophage recruitment, driving inflammation, fibrosis, and structural kidney damage. Early biomarkers that can serve as risk markers for progression of diabetic kidney disease (DKD) are needed. We investigated whether circulating VICM — a fragment of citrullinated, MMP-degraded vimentin — is a risk marker for progression of DKD in people with type 2 diabetes (T2D) and microalbuminuria. Methods: Serum VICM was measured at baseline using the nordicVICMTM ELISA in 196 participants with T2D, microalbuminuria, but normal kidney function. DKD progression was defined as a >30% decline in eGFR. Cox proportional hazards models were applied; non-normal distributed variables were log2-transformed. Hazard ratios (HRs) are per doubling. Results: The cohort was 75% male, median age was 60 (59-61) years, eGFR 91 (87-94) ml/min/1.73 m2, and UAER 104 (80-131) mg/24 h. Levels of VICM correlated with hsCRP (r=0.26, p<0.001) and urinary KIM-1 (0.32, p<0.0001). Data on DKD progression were available for 173 (88%) participants. Over a median follow-up of 4.6 years, higher VICM was associated with a higher risk of DKD progression (HR: 1.56 [95% CI: 1.14-2.15], n=42/173). After adjustment for age, sex, baseline eGFR, and UAER, the association remained significant (HR: 1.50 [1.05-2.13], n=41/169). In sensitivity analyses, further adjusted for BMI, HbA1c, systolic BP, LDL, smoking, urinary KIM-1, and inflammatory markers (hsCRP, YKL-40, IL-6, TNF-α, GDF-15) yielded a HR of 1.65 [1.06-2.57], n=39/156. Conclusion: Higher VICM was an independent risk marker of DKD progression in people with T2D and microalbuminuria. Biomarkers reflecting macrophage-driven immune dysregulation, such as VICM, may enable early identification of people at high risk of DKD progression. Disclosure: A.L. Møller: None. B. von Scholten: Employee; Current; Novo Nordisk A/S. P. Rossing: Advisory Panel; Ended; Abbott Diagnostics. Advisory Panel; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Eli Lilly and Company. Consultant; Current; Lexicon Pharmaceuticals, Inc., Roche Pharmaceuticals. Consultant; Ended; Amgen Inc.