Diabetes Control and the Risks of ESRD and Mortality in Patients With CKD

Abstract

Background: Diabetes is the leading cause of end-stage renal disease (ESRD) and a significant contributor to mortality in the general population. We examined the associations of hemoglobin A_1c (HbA_1c) levels with ESRD and death in a population with diabetes and chronic kidney disease (CKD).

Study design: Cohort study.

Setting & participants: 6,165 patients with diabetes (treated with oral hypoglycemic agents and/or insulin) and CKD stages 1 to 5 at a large health care system.

Predictor: HbA_1c level (examined as a categorical and continuous measure).

Outcomes: All-cause and cause-specific mortality ascertained from the Ohio Department of Health mortality files and ESRD ascertained from the US Renal Data System.

Results: During a median 2.3 years of follow-up, 957 patients died (887 pre-ESRD deaths) and 205 patients reached ESRD. In a Cox proportional hazards model, after multivariable adjustment including for kidney function, HbA_1c level < 6% was associated with higher risk for death when compared with HbA_1c levels of 6% to 6.9% (HR, 1.23; 95% CI, 1.01-1.50). Similarly, HbA_1c level ≥ 9% was associated with higher risk for all-cause death (HR, 1.34; 95% CI, 1.06-1.69). In competing-risk models, baseline HbA_1c level was not associated with ESRD. For cause-specific mortality, diabetes accounted for >12% of deaths overall and >19% of deaths among those with HbA_1c levels > 9%.

Limitations: Small proportion of participants with advanced kidney disease; single-center population.

Conclusions: In this cohort of patients with CKD with diabetes, HbA_1c levels < 6% and ≥9% were associated with higher risk for death. HbA_1c levels were not associated with ESRD in this specific CKD population. Diabetes-related deaths increased with higher HbA_1c levels.

Keywords: Glycated hemoglobin; HbA(1c); chronic kidney disease (CKD); death and kidney disease; diabetes control; diabetes mellitus; diabetic nephropathy; end stage renal disease (ESRD); incident ESRD; mortality.

Figure 1

Cumulative incidence curves for end-stage renal disease (ESRD) and death among patients with chronic kidney disease across hemoglobin A_1c categories using competing risks.

Figure 2

Associations of hemoglobin A_1c (HbA_1c) with all-cause mortality (baseline HbA_1c considered as continuous measure with splines at the 10th, 50th, and 90th percentile: 5.8, 6.9, and 9.1 respectively; main effect P = 0.07, nonlinear P = 0.04).