Glycemic Monitoring and Management in Advanced Chronic Kidney Disease

Abstract

Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.

Keywords: CGM; CKD; diabetes mellitus; end-stage renal disease; glucose and insulin metabolism; hemoglobin A1c; hypoglycemia; hypoglycemic agents therapeutic use; insulin therapeutic use; practice guidelines.

Graphical Abstract

Figure 1.

A, Insulin and glucose metabolism by the liver, fat and muscle tissues, and kidney with normal renal function. B, Insulin and glucose metabolism by the kidney, fat and muscle tissues, and pancreas in early chronic kidney disease (CKD) resulting in higher risk of hyperglycemia. C, Insulin and glucose metabolism by the kidney, fat and muscle tissues, and pancreas in advanced CKD and hemodialysis (HD) resulting in higher risk of hypoglycemia. RBC, red blood cells

Figure 2.

Association of mean hemoglobin A_1c and adjusted all-cause mortality risk in patients with diabetes on hemodialysis: results of a meta-analysis of 10 studies (n = 83 684 patients).

Figure 3.

Limitations of glycemic biomarkers (hemoglobin A_1c [HbA_1c], fructosamine, and glycated albumin) in patients with advanced chronic kidney disease (CKD)