How does dialysis affect Hemoglobin A1c (HbA1c) levels?

Impact of Dialysis on HbA1c Measurements

HbA1c measurements in dialysis patients can be inaccurate and may underestimate actual glycemic control, requiring supplementary monitoring methods such as continuous glucose monitoring or glycated albumin for optimal management. 1

Factors Affecting HbA1c Accuracy in Dialysis Patients

Factors causing falsely decreased HbA1c values:

• Reduced red blood cell lifespan due to uremia 1
• Hemolysis during hemodialysis procedures 1
• Blood transfusions 1
• Iron supplementation (can decrease HbA1c by 0.5-0.7%) 1
• Erythropoietin-stimulating agent administration 1

Factors causing falsely increased HbA1c values:

• Carbamylation of hemoglobin 1
• Acidosis 1

Evidence on HbA1c-Glucose Relationship in Dialysis

Research findings on the relationship between HbA1c and glucose levels in dialysis patients show mixed results:

• Some studies found no significant difference in the HbA1c-glucose relationship between patients with normal kidney function and those with kidney failure 1
• Other studies reported 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
• Inaba et al. found shallower regression slopes for the HbA1c-glucose relationship in hemodialysis patients 1
• At lower glucose levels (around 160 mg/dL and HbA1c 7.5%), hemodialysis patients tend to have higher glucose levels for a given HbA1c value 1
• In peritoneal dialysis patients, mean sensor glucose was found to be 0.98 mmol/L higher than estimated mean plasma glucose derived from HbA1c 2

Clinical Implications

Despite these limitations, the KDOQI guidelines state that:

• HbA1c remains the best clinical marker of long-term glycemic control in dialysis patients, particularly when combined with self-monitoring of blood glucose 1
• The modest changes in HbA1c with decreasing eGFR and even with hemodialysis do not appear to be of clinical significance compared to the wide inter-individual variability 1
• Neither hemodialysis nor peritoneal dialysis acutely changes HbA1c levels 1

Alternative Glycemic Markers for Dialysis Patients

When HbA1c reliability is questionable, consider these alternatives:

1. Glycated albumin:

   • Reflects glycemic control over a 2-week period 1
   • May be a better predictor of mortality and hospitalizations than HbA1c in dialysis patients 1
   • Less affected by factors that influence HbA1c 3
   • Limitation: Can be affected by hypoalbuminemia common in ESKD 1

2. Fructosamine:

   • Reflects glycemia over 2-4 weeks 3
   • Shows significant association with mean sensor glucose in peritoneal dialysis patients 2
   • Limitation: Can be inaccurate due to hypoalbuminemia 1

3. Continuous glucose monitoring (CGM):

   • Provides comprehensive evaluation of glycemic excursions over 24 hours 3
   • Recent studies show that in hemodialysis patients, glucose management indicator (GMI) from CGM has a strong correlation with time-in-range metrics 4
   • HbA1c underestimated the average glucose and GMI in patients with diabetes and ESKD treated by hemodialysis 4

Practical Recommendations for Clinicians

1. Continue using HbA1c as the primary marker for long-term glycemic control, but interpret results with caution 1, 3

2. Supplement HbA1c with:

   • Regular self-monitoring of blood glucose 1
   • Consider continuous glucose monitoring when available 4
   • Consider glycated albumin or fructosamine when HbA1c reliability is particularly questionable 3, 2

3. Be aware of potential discrepancies:

   • Up to 49% of dialysis patients may have a discordance of >1% between HbA1c and glucose management indicator 4
   • HbA1c may underestimate actual glycemic control in many dialysis patients 2

4. Avoid over-reliance on HbA1c alone for treatment decisions in dialysis patients, especially when clinical picture doesn't match the HbA1c value 5

Pitfalls to Avoid

• Don't assume that HbA1c targets for the general diabetic population apply directly to dialysis patients 1
• Be cautious about tight glycemic control in dialysis patients due to increased risk of hypoglycemia 1
• Don't rely solely on column chromatography methods for HbA1c measurement as they can measure carbamylated hemoglobin with HbA1c, leading to falsely high concentrations in renal failure 6
• Avoid making treatment decisions based on HbA1c alone without considering the patient's clinical status, risk of hypoglycemia, and other glycemic markers 5