Novel Protein Biomarkers to Monitor Kidney Function Decline and Treatment Response in Individuals With Normoalbuminuria and Type 2 Diabetes.

Kidney function can decline in individuals with type 2 diabetes despite normal albuminuria, yet current risk stratification relies heavily on urinary albumin-to-creatinine ratio (UACR), which may inadequately capture this process. We investigated whether biomarkers reflecting inflammation, tubular injury, regenerative capacity, and fibrosis improve risk prediction and treatment monitoring beyond UACR in these individuals. Baseline UACR did not predict the composite kidney outcome, whereas TNFR-1, TNFR-2, KIM-1, and MMP-7 were independently associated. In those who developed the outcome, these biomarkers and uEGF/Cr showed divergent trajectories, unlike UACR. Biomarkers capturing pathways beyond glomerular injury may improve risk stratification and treatment monitoring in these normoalbuminuric patients.