Glycated Hemoglobin Level and Mortality in a Nondiabetic Population with CKD

Background and objectives

Glycated hemoglobin (HbA_1c) is used to diagnose diabetes mellitus (DM) and guide its management. The association between higher HbA_1c and progression to ESRD and mortality has been demonstrated in populations with DM. This study examined the association between HbA_1c and these end points in a population with CKD and without DM.

Design, setting, participants, & measurements

In the hospital-based NephroTest cohort study, measured GFR (mGFR) was taken by ⁵¹Cr-EDTA renal clearance and HbA_1c in 1165 adults with nondialysis CKD stages 1–5 and without DM between January 2000 and December 2010. The median follow-up was 3.48 years (interquartile range, 1.94–5.82) for the competing events of ESRD and pre-ESRD mortality. Time-fixed and time-dependent Cox models were used to estimate hazard ratios (HRs) for ESRD and mortality according to HbA_1c, treated continuously or in tertiles.

Results

At inclusion, the mean mGFR was 42.2±19.9 ml/min per 1.73 m², and the mean HbA_1c value was 5.5%±0.5%. During follow-up, 109 patients died, and 162 patients reached ESRD. Pre-ESRD mortality was significantly associated with HbA_1c treated continuously: for every 1% higher HbA_1c, the crude HR was 2.16 (95% confidence interval [95% CI], 1.27 to 3.68), and it was 1.85 (95% CI, 1.05 to 3.24) after adjustment for mGFR and other risk factors of death. After excluding incident diabetes over time, the updated mean of HbA_1c remained significantly associated with higher mortality risk: adjusted HR for the highest (5.7%–6.4%) versus the lowest tertile (<5.3%) was 2.62 (95% CI, 1.16 to 5.91). There was no association with ESRD risk after adjustment for risk factors of CKD progression.

Conclusions

In a CKD cohort, HbA_1c values in the prediabetes range are associated with mortality. Such values should be therefore included among the risk factors for negative outcomes in CKD populations.