Can glycated hemoglobin (HbA1c) be used to assess glycemic control in patients with chronic kidney disease?

Can HbA1c Be Used in CKD Patients?

Yes, HbA1c can be used in CKD patients, but its reliability decreases significantly as kidney function declines, particularly below eGFR 30 mL/min/1.73 m², and it should be supplemented with glucose monitoring or alternative markers in advanced CKD (stages 4-5). 1, 2

HbA1c Reliability by CKD Stage

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

• HbA1c remains the preferred glycemic biomarker and maintains acceptable accuracy in CKD stages 1-3b. 2
• The correlation between HbA1c and actual glucose levels remains intact with no clinically significant bias requiring alternative markers down to eGFR 30 mL/min/1.73 m². 2
• Continue using HbA1c as the primary monitoring tool with standard interpretation in this population. 2

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

• HbA1c significantly underestimates glycemic control in advanced CKD and should be interpreted with extreme caution. 1, 2, 3
• The correlation between HbA1c and mean glucose is substantially reduced (r = 0.520 in advanced CKD vs r = 0.630 with normal renal function). 2
• Patients on hemodialysis tend to have higher actual glucose levels for any given HbA1c value, particularly at lower glucose ranges (160 mg/dL corresponding to HbA1c 7.5%). 2

Factors Causing HbA1c Inaccuracy in Advanced CKD

Factors That Falsely Lower HbA1c

• Shortened red blood cell lifespan from uremia is the primary mechanism reducing HbA1c reliability. 1, 2
• Erythropoietin-stimulating agents reduce HbA1c by 0.5-0.7% through formation of new red cells with less glycation time. 2
• Iron supplementation decreases HbA1c values. 2
• Hemolysis during hemodialysis procedures lowers HbA1c. 1, 2
• Blood transfusions artificially reduce HbA1c. 2

Factors That Falsely Elevate HbA1c

• Carbamylation of hemoglobin due to elevated blood urea nitrogen creates carbamylated hemoglobin that certain assays cannot distinguish from glycated hemoglobin. 1, 2
• Metabolic acidosis can falsely elevate HbA1c measurements. 2

Recommended Monitoring Strategy by CKD Stage

For CKD Stages 1-3b

• Use HbA1c as the primary glycemic monitoring tool without modification. 2
• Target HbA1c 7-8% based on NKF-KDOQI guidelines to balance glycemic control against hypoglycemia risk. 1

For CKD Stages 4-5 and Dialysis

• Continue measuring HbA1c but supplement with self-monitored blood glucose or continuous glucose monitoring (CGM) for accurate assessment. 1, 2, 4
• CGM is the preferred alternative as it is not affected by kidney function and provides the most accurate assessment of glycemic patterns. 1, 2
• Consider glycated albumin as an alternative marker, which correlates significantly with mean glucose in CKD stages 4-5 and outperforms HbA1c. 2, 3
• The GA/HbA1c ratio is significantly higher in CKD patients (2.5 ± 0.4) compared to controls (2.2 ± 0.4), indicating HbA1c underestimation. 3

Alternative Glycemic Markers

Glycated Albumin

• Glycated albumin more accurately reflects glycemic control compared to HbA1c in advanced CKD (stages 4-5). 5, 3
• It reflects glycemic control over 2-4 weeks rather than 2-3 months. 1
• Glycated albumin predicts all-cause and cardiovascular mortality in chronic hemodialysis patients. 1
• Limitation: The assay is biased low by hypoalbuminemia, common in CKD due to proteinuria, malnutrition, or peritoneal dialysis. 1

Fructosamine

• Reflects glycemia over 2-4 weeks. 1
• Limitation: The assay is biased high by hypoalbuminemia and is not accurate for eGFR <30 mL/min. 1
• Has insufficient accuracy for overall glycemic control and limited availability. 1

Continuous Glucose Monitoring

• CGM provides superior assessment of glycemic patterns, hypoglycemia detection, and insulin needs in advanced CKD and dialysis patients. 1, 2
• CGM-derived metrics (time in range, time in hypoglycemia, glucose variability) are not affected by altered red blood cell turnover. 1
• Factory-calibrated devices (Abbott FreeStyle Libre, Dexcom G6) reduce burden by eliminating fingerstick calibrations. 1
• CGM allows calculation of glucose management indicator (GMI), which may be more useful than HbA1c in advanced CKD. 1

Critical Clinical Pitfalls to Avoid

• Never rely solely on HbA1c for glycemic assessment in CKD stages 4-5 or dialysis patients, as it systematically underestimates true glycemia. 1, 2, 4
• Do not assume good glycemic control based on low HbA1c values in advanced CKD without confirming absence of hypoglycemia through glucose monitoring. 2
• Be aware that glucose meter interferences can occur: GDH-PQQ-based meters falsely elevate readings in patients using icodextrin-containing peritoneal dialysis solutions, potentially masking true hypoglycemia. 1
• When HbA1c seems discordant with symptoms or self-monitored glucose values in advanced CKD, prioritize direct glucose measurements over HbA1c. 2
• Do not use fructosamine as an alternative in patients with eGFR <30 mL/min due to poor accuracy. 1