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Atherosclerosis Risk in Communities (ARIC) Study

Lori D. Bash, MPH; Elizabeth Selvin, PhD, MPH; Michael Steffes, MD, PhD; Josef Coresh, MD, PhD, MHS; Brad C. Astor, PhD, MPH, MS

Arch Intern Med. 2008;168(22):2440-2447.

Background  Diabetic nephropathy is the leading cause of kidney failure in the United States. The extent to which an elevated glycated hemoglobin (HbA_1c) concentration is associated with increased risk of chronic kidney disease (CKD) in the absence of albuminuria and retinopathy, the hallmarks of diabetic nephropathy, is uncertain.

Methods  Glycated hemoglobin concentration was measured in 1871 adults with diabetes mellitus followed up for 11 years in the Atherosclerosis Risk in Communities (ARIC) Study. Incident CKD was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m² after 6 years of follow-up or a kidney disease–related hospitalization. We categorized HbA_1c concentrations into 4 clinically relevant categories. Albuminuria and retinopathy were measured midway through follow-up.

Results  Higher HbA_1c concentrations were strongly associated with risk of CKD in models adjusted for demographic data, baseline glomerular filtration rate, and cardiovascular risk factors. Compared with HbA_1c concentrations less than 6%, HbA_1c concentrations of 6% to 7%, 7% to 8%, and greater than 8% were associated with adjusted relative hazard ratios (95% confidence intervals) of 1.4 (0.97-1.91), 2.5 (1.70-3.66), and 3.7 (2.76-4.90), respectively. Risk of CKD was higher in individuals with albuminuria and retinopathy, and the association between HbA_1c concentration and incident CKD was observed even in participants without either abnormality: adjusted relative hazards, 1.46 (95% confidence intervals, 0.80-2.65), 1.17 (0.43-3.19), and 3.51 (1.67-7.40), respectively; P_trend = .004.

Conclusions  We observed a positive association between HbA_1c concentration and incident CKD that was strong, graded, independent of traditional risk factors, and present even in the absence of albuminuria and retinopathy. Hyperglycemia is an important indicator of risk of both diabetic nephropathy with albuminuria or retinopathy and of less specific forms of CKD.

Author Affiliations: Departments of Epidemiology (Ms Bash and Drs Selvin, Coresh, and Astor) and Biostatistics (Dr Coresh), The Johns Hopkins Bloomberg School of Public Health; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University (Ms Bash and Drs Selvin, Coresh, and Astor); and Department of Medicine, The Johns Hopkins University School of Medicine (Drs Coresh and Astor), Baltimore, Maryland; and Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis (Dr Steffes).

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