How does End-Stage Renal Disease (ESRD) affect Hemoglobin A1c (HbA1c) measurements?

Effect of End-Stage Renal Disease on HbA1c Measurement

HbA1c remains the best clinical marker of long-term glycemic control in patients with diabetes and ESRD, but its interpretation requires caution due to multiple factors that can affect its accuracy. 1

How ESRD Affects HbA1c Measurements

ESRD can impact HbA1c measurements in opposing ways, leading to both falsely decreased and falsely increased values:

Factors causing falsely decreased HbA1c:

• Reduced red blood cell lifespan due to uremia
• Blood transfusions
• Hemolysis
• Use of erythropoietin-stimulating agents (decreases HbA1c by 0.5-0.7%)
• Iron supplementation (decreases HbA1c by 0.5-0.7%)
• Anemia (common in advanced CKD)

Factors causing falsely increased HbA1c:

• Carbamylation of hemoglobin
• Metabolic acidosis
• Advanced glycation end-product formation
• Repetitive exposure to high glucose levels in dialysate 2

Correlation Between HbA1c and Blood Glucose in ESRD

Studies show conflicting results regarding the relationship between HbA1c and glucose levels in ESRD patients:

• Some studies found no difference in the HbA1c-glucose relationship between patients with normal kidney function and those with kidney failure 1
• Other studies reported that hemodialysis patients had lower correlation of plasma glucose levels with HbA1c (r=0.520) compared to those with normal kidney function (r=0.630) 1
• At lower glucose levels (160 mg/dL and HbA1c 7.5%), hemodialysis patients tend to have higher glucose levels for a given HbA1c 1
• HbA1c values above 7.5% may overestimate hyperglycemia in ESRD patients 3

Clinical Implications

Despite these limitations, the KDOQI clinical practice guideline states that:

1. HbA1c remains the best clinical marker of long-term glycemic control, particularly when combined with self-monitoring of blood glucose 1
2. The modest changes in HbA1c with decreasing eGFR (from 75 to 15 mL/min/1.73 m²) and even with hemodialysis do not appear to be of clinical significance compared to the wide inter-individual variability 1
3. Neither hemodialysis nor peritoneal dialysis acutely change HbA1c levels 1

Alternative Glycemic Markers in ESRD

When HbA1c reliability is questionable in advanced CKD:

• Glycated albumin: Reflects glycemic control over a 2-week period and may be a better predictor of mortality and hospitalizations than HbA1c in dialysis patients 1, 4

  • However, it can be affected by hypoalbuminemia, which is common in CKD 1

• Fructosamine: Reflects glycemia over 2-4 weeks

  • Can be falsely elevated in hypoalbuminemia 1

• Continuous glucose monitoring (CGM): Provides comprehensive evaluation of glycemic excursions over 24 hours and can aid in achieving glycemic targets 1

  • Studies show 97.9-99.1% of CGM readings in hemodialysis patients fall within clinically acceptable zones 1

Practical Approach to Glycemic Monitoring in ESRD

1. Use HbA1c as the primary marker for long-term glycemic control
2. Combine with self-monitoring of blood glucose or CGM for daily management
3. Consider glycated albumin when HbA1c reliability is questionable
4. Be aware that an HbA1c of 6-7% estimates glycemic control similarly to patients without severe renal impairment 3
5. For HbA1c values above 7.5%, consider the possibility of overestimation of hyperglycemia 3

Important Caveats

• High HbA1c levels and glycemic variability increase the risk of severe hypoglycemia in diabetic hemodialysis patients 5
• The mean blood glucose value calculated from HbA1c may not reflect the actual mean blood glucose measured by CGM in ESRD patients 6
• ESRD patients have larger glycemic fluctuations compared to non-diabetic ESRD patients 6
• Hemodialysis itself can cause reduction in mean blood glucose and glycemic variability 6

By understanding these limitations and using a combination of monitoring tools, clinicians can better manage glycemic control in ESRD patients to improve outcomes.