HbA1c-dependent projection of long-term renal outcomes.

Background: Diabetes mellitus is a major risk factor for the development of chronic kidney disease (CKD). There is limited data addressing the value of glycated hemoglobin (HbA1c) to predict renal outcomes independent of diabetes status.

Methods: This single-center retrospective observational study presents data of 19,285 subjects, irrespective of initial CKD or diabetes status. The primary endpoint was defined as the time to manifestation of moderate CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m ) in subjects with eGFR ≥60 mL/min/1.73 m at baseline. The secondary endpoint was defined as time to progression of CKD (eGFR <30 mL/min/1.73 m ) in subjects with eGFR 30-60 mL/min/1.73 m . Multivariate time-to-event and logistic regression models were applied to estimate the influences of HbA1c, sex, age, eGFR, triglycerides, and cholesterol on both endpoints.

Results: Lowest baseline HbA1c levels were associated with the slowest decline of kidney function (median time to manifestation of moderate CKD for HbA1c <5.7%: 15.9 years [95% confidence interval (CI): 15.2-16.7]; for HbA1c 5.7%-6.5%: 14.5 years [95% CI: 14.0-15.1]; for HbA1c 6.5%-8.5%: 11.1 years [95% CI: 10.4-11.7]; for HbA1c >8.5%: 8.3 years [95% CI: 7.8-9.2]; p < 0.001). Similar results were observed for the secondary endpoint. Covariate-adjusted time-to-event analysis demonstrated an almost linear correlation between continuous baseline HbA1c levels and the probabilities of reaching both endpoints.

Conclusions: HbA1c levels are a strong predictor for eGFR decline, irrespective of diabetes status or CKD stage, demonstrating a tight concentration-dependent relationship. This association becomes apparent in the prediabetic HbA1c range and remains constant over the entire HbA1c spectrum.