At baseline, median levels of TNFR1 and TNFR2 were roughly two-fold higher in the advanced than in the early cohort. TNFR1 and TNFR2 levels were associated with higher risk of eGFR decline in T2DM persons with both early (ACCORD) and established (VA-NEPHRON-D) DKD. In both cohorts, patients who reached the renal outcome had higher baseline TNFRs levels. This evidence concerns the gene TNFRSF1B and type 2 diabetes mellitus.