Introduction and Objective: Glycemic targets in advanced CKD are unclear; we assessed HbA1c associations with CVD, kidney failure, and mortality in diabetes by baseline eGFR. Methods: In the Chronic Renal Insufficiency Cohort (CRIC), we studied 2,801 participants with diabetes stratified by baseline eGFR (preserved ≥45 vs reduced 45 mL/min/1.73 m²). Multivariable Cox models estimated adjusted hazard ratios (HRs) for major adverse cardiovascular events (MACE), kidney failure, and all-cause mortality across HbA1c categories (reference 6.5-7.5%). Effect modification by eGFR was evaluated using restricted cubic splines with HbA1c-by-eGFR interaction. Results: eGFR significantly modified the HbA1c-MACE association (P-interaction=0.01). With preserved eGFR, HbA1c 5.7-6.5% was associated with lower MACE risk versus reference (HR 0.65; 95% CI 0.47-0.90) (Panel B). With reduced eGFR, this benefit was attenuated (HR 0.89; 95% CI 0.70-1.14) (Panel B). In reduced eGFR, HbA1c 5.7% was associated with higher all-cause mortality (HR 1.54; 95% CI 1.13-2.10) (Panel B). Spline analyses showed the hazard ratio for intensive control crossed 1.0 as eGFR declined below ~45 mL/min/1.73 m², consistent with diminishing benefit/futility (Panel A). Conclusion: Lower HbA1c reduced CVD risk with eGFR ≥45, but not with eGFR 45, where very low HbA1c increased mortality—supporting tighter targets for eGFR ≥45 and more conservative goals for eGFR 45. Disclosure B. Nadim: None. A. Verma: None.
NADIM et al. (2026) studied this question.