Is A1c (Hemoglobin A1c) an unreliable marker for Diabetes Mellitus (DM) in patients with End-Stage Renal Disease (ESRD) on dialysis?

A1c is an Unreliable Marker for Diabetes Mellitus in Patients on Dialysis

HbA1c is not a reliable marker for glycemic control in patients with end-stage renal disease (ESRD) on dialysis due to multiple factors that can falsely alter its values, making it a problematic tool for diabetes management in this population. 1

Why HbA1c is Unreliable in Dialysis Patients

Factors That Falsely Lower HbA1c Values

• Reduced red blood cell lifespan - Dialysis patients have shortened erythrocyte survival time 1
• Hemolysis - More common in ESRD patients 1
• Iron deficiency - Prevalent in dialysis patients 1
• Blood transfusions - Often required in this population 1
• Erythropoietin therapy - Can reduce HbA1c by 0.5-0.7% due to formation of new red cells 1
• Increased erythrocyte glucose uptake during hemodialysis 1

Factors That Falsely Elevate HbA1c Values

• Carbamylation of hemoglobin - Due to uremia 1
• Acidosis - Common in ESRD 1
• Repetitive exposure to high glucose dialysate - Can artificially elevate HbA1c 2

Evidence of Poor Correlation with Actual Glycemia

Multiple studies demonstrate that HbA1c correlates poorly with actual blood glucose levels in dialysis patients:

• Inaba et al. found lower correlation of plasma glucose levels with HbA1c in hemodialysis patients (r = 0.520) compared to those with normal kidney function (r = 0.630) 1
• Joy et al. demonstrated that an HbA1c increase of 1% correlated with a change in mean glucose of only 20 mg/dL in hemodialysis patients versus 30 mg/dL in those with normal kidney function 1
• Riveline et al. found a shallower regression slope for hemodialysis patients, indicating that at lower glucose levels, hemodialysis patients tended to have higher glucose levels for a given HbA1c 1

Alternative Monitoring Approaches

Preferred Monitoring Methods

• Self-monitoring of blood glucose (SMBG) - Provides immediate glycemic information 1
• Continuous glucose monitoring (CGM) - Emerging data suggest promise for more precise monitoring and treatment adjustments 1
• Glycated albumin or fructosamine - May be alternatives, though not fully validated 1

Target Ranges

• Based on observational data for associations with mortality, an HbA1c range of 7% to 8% appears most favorable for dialysis patients if HbA1c must be used 1
• However, this should be interpreted with caution given the unreliability of the measurement

Clinical Implications

• Relying solely on HbA1c may lead to inappropriate treatment decisions:

  • Falsely low values may result in undertreatment and increased risk of hyperglycemia
  • Falsely high values may lead to overtreatment and dangerous hypoglycemia

• Hypoglycemia risk is already elevated in dialysis patients due to:

  • Impaired kidney gluconeogenesis
  • Impaired insulin clearance
  • Defective insulin degradation due to uremia
  • Impaired counterregulatory hormone responses 1

Practical Recommendations

1. Use multiple methods to assess glycemic control rather than relying solely on HbA1c
2. Implement regular SMBG with attention to both pre- and post-dialysis values
3. Consider CGM when available for more comprehensive glycemic patterns
4. Be cautious with HbA1c interpretation - values may not reflect true glycemic status
5. Adjust treatment targets - conventional HbA1c targets may not be appropriate for dialysis patients

In conclusion, while HbA1c remains in use due to lack of fully validated alternatives, clinicians should recognize its significant limitations in dialysis patients and incorporate additional glycemic monitoring methods for more accurate assessment and safer diabetes management.