Management of Hyperglycemia in Diabetic Kidney Disease.

Abstract

The growing incidence and prevalence of diabetes has made a significant impact on the development of diabetic kidney disease (DKD) (1). DKD is among the most frequent complications of diabetes; indeed, diabetes accounts for ∼50% of all cases of end-stage renal disease (ESRD) in developed countries (2). Patients often have comorbid diabetes and chronic kidney disease (CKD). Although intensive glycemic management has been shown to delay the onset and progression of increased urinary albumin excretion and reduced estimated glomerular filtration rate (eGFR) in diabetes patients (3), conservative dose selection and adjustment of antidiabetic medications is necessary to balance glycemic control with safety. A1C has limitations related to its precision and interpretation in the CKD population (4), with erythrocyte turnover being a major cause of A1C imprecision in this population. Red blood cell survival times become shorter as eGFR falls, resulting in a reduction in measured A1C. Treatment with erythrocyte-stimulating agents lowers A1C further, perhaps because of changes in hemoglobin concentrations (5,6). Observational data support the notion that higher A1C levels in nondialysis diabetes patients with CKD stages 3–5 (eGFR levels <60 mL/min/1.73 m2) are associated with worse outcomes, including progression of kidney disease (7). However, these patients are at higher risk for hypoglycemic events (8). Factors that may contribute to this increased risk can include slowed elimination of hypoglycemic agents, alcohol intake, chronic malnutrition, acute caloric deprivation, and decreased renal gluconeogenesis as kidney function declines (8–10). In the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, when compared with patients with normal renal function, those with baseline serum creatinine of 1.3–1.5 mg/dL had a 66% increased risk of severe hypoglycemia (11). A U-shaped relationship between A1C and mortality has been demonstrated, suggesting that hypoglycemia may be one reason for higher mortality in those …