Poor glycemic control in diabetes and the risk of incident chronic kidney disease even in the absence of albuminuria and retinopathy: Atherosclerosis Risk in Communities (ARIC) study

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 m ² 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.