Can HbA1c (hemoglobin A1c) be relied upon to assess glycemic control in patients with chronic kidney disease (CKD) and diabetes?

Can HbA1c Be Relied Upon in CKD Diabetic Patients?

HbA1c remains the preferred glycemic biomarker for monitoring diabetic patients with CKD stages 1-3b (eGFR ≥30 mL/min/1.73 m²), but becomes increasingly unreliable in advanced CKD (stages 4-5) and dialysis patients, where continuous glucose monitoring or glycated albumin should be considered as alternatives. 1

Reliability by CKD Stage

Early to Moderate CKD (Stages 1-3a, eGFR ≥45 mL/min/1.73 m²)

• HbA1c accuracy and precision do not vary significantly from normal kidney function down to an eGFR of 30 mL/min/1.73 m², making it reliable for routine monitoring in this population 1, 2
• The correlation between HbA1c and actual glucose levels remains intact, with no clinically significant bias requiring alternative markers 1
• Standard HbA1c measurement frequency applies: twice yearly if stable and meeting targets, quarterly if not at goal or after treatment changes 2

Advanced CKD (Stages 4-5, eGFR <30 mL/min/1.73 m²)

• HbA1c significantly underestimates glycemic control in CKD stages 4-5, with values typically 0.5-1.0% lower than expected for actual glucose levels 3, 4
• The correlation between plasma glucose and HbA1c deteriorates substantially (r = 0.38 in CKD vs r = 0.66 in normal kidney function) 1, 3
• At glucose levels around 160 mg/dL, dialysis patients may have HbA1c values 0.5-1.5% lower than non-CKD patients with identical glucose exposure 1, 5

Factors Causing HbA1c Inaccuracy in Advanced CKD

Factors That Lower HbA1c (More Common)

• Shortened red blood cell lifespan from uremia is the primary mechanism reducing HbA1c reliability 1
• Erythropoietin-stimulating agents reduce HbA1c by 0.5-0.7% through formation of new red cells with less glycation time 1, 5
• Iron supplementation similarly decreases HbA1c by promoting new RBC formation 1, 5
• Hemolysis during hemodialysis sessions removes glycated hemoglobin 1
• Blood transfusions introduce non-glycated hemoglobin, diluting the HbA1c measurement 1, 5

Factors That Raise HbA1c (Less Common)

• Carbamylation of hemoglobin from elevated urea falsely increases HbA1c 1, 5
• Metabolic acidosis can artifactually elevate HbA1c values 1, 5

Alternative Monitoring Strategies

Continuous Glucose Monitoring (CGM)

• CGM is not affected by kidney function and provides the most accurate assessment of glycemic control in advanced CKD and dialysis patients 1
• The glucose management indicator (GMI) derived from CGM correlates strongly with time-in-range (r = -0.96) and more accurately reflects glucose exposure than HbA1c in dialysis patients 4
• In dialysis patients, 49% show >1% discordance between HbA1c and GMI, with HbA1c consistently underestimating true glycemic burden 6, 4
• CGM should be considered when HbA1c is discordant with clinical symptoms or directly measured glucose levels 1, 7

Glycated Albumin

• Glycated albumin correlates significantly with mean glucose in CKD stages 4-5 (r = 0.54) and outperforms HbA1c (r = 0.38) as a glycemic marker 3
• The GA/HbA1c ratio is significantly elevated in CKD patients (2.5 ± 0.4 vs 2.2 ± 0.4 in controls), indicating HbA1c underestimation 3
• Glycated albumin reflects 2-3 week glucose exposure and predicts mortality and hospitalization rates better than HbA1c in dialysis patients 1, 5, 8
• Limitation: Hypoalbuminemia (common in ESKD) can reduce glycated albumin levels, though it remains more reliable than HbA1c 1
• Practical barrier: Limited availability in real-world clinical settings restricts widespread use 1

Fructosamine

• Fructosamine reflects 2-3 week glycemic control but correlates more poorly with glucose than both HbA1c and glycated albumin in CKD 1
• Hypoalbuminemia (common in ESKD) significantly reduces fructosamine accuracy 1
• Not recommended as a primary alternative to HbA1c 1

Clinical Implications and Recommended Approach

For CKD Stages 1-3b (eGFR ≥30 mL/min/1.73 m²)

• Continue using HbA1c as the primary monitoring tool with standard interpretation 1, 2
• Target HbA1c between 6.5-8.0% based on hypoglycemia risk, comorbidities, life expectancy, and treatment propensity for hypoglycemia 1, 2
• No adjustment to HbA1c interpretation is needed 1

For CKD Stages 4-5 and Dialysis (eGFR <30 mL/min/1.73 m²)

• Interpret HbA1c values with extreme caution, recognizing they likely underestimate true glycemic exposure by 0.5-1.5% 1, 5, 3
• Consider the actual HbA1c value as potentially 0.5-1.0% higher when making treatment decisions 5, 4
• Strongly consider CGM for accurate assessment, particularly when HbA1c seems discordant with symptoms or self-monitored glucose values 1, 7
• If CGM unavailable, increase frequency of self-monitoring blood glucose to supplement HbA1c interpretation 1
• Request glycated albumin if available, as it provides superior accuracy in this population 3, 8

Critical Pitfalls to Avoid

• Do not assume HbA1c <7% represents adequate control in dialysis patients—this may correspond to mean glucose levels warranting treatment intensification 3, 4
• Do not aggressively target HbA1c <6.5% in advanced CKD, as both very low (<5.4%) and very high (≥8.5%) HbA1c values associate with increased mortality in dialysis patients 1, 9
• Do not rely solely on HbA1c when initiating or adjusting insulin or sulfonylureas in advanced CKD, as underestimation of true glucose levels combined with these hypoglycemia-prone agents creates dangerous risk 1
• Do not ignore the wide inter-individual variability in the glucose-HbA1c relationship in CKD—two patients with identical HbA1c values may have substantially different actual glucose exposures 1, 5