Is HbA1c A Reliable Test In Patients With Diabetes And Renal Disease?
- Volume 22 - Issue 8 - August 2009
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How Hemodialysis Complicates The Diagnostic Picture
Hemoglobin A1c is the most widely used assay for evaluation of long-term glycemic control and is strongly correlated with adverse outcome risk. Moreover, the well established risks of diabetic microvascular and macrovascular complications are strongly associated with the HbA1c level in patients with both type 1 and type 2 diabetes. In general, a HbA1c <7% is associated with the projected reduction in diabetic complications over time.4 However, multiple studies have recently reported that HbA1c may not provide a relevant assay for glycemic control in hemodialysis patients.4,5,8
Hemoglobin A1c is the product of chemical condensation of circulating hemoglobin that has reacted with glucose and thus is influenced by factors other than glucose alone.4,5 The uremic environment, blood loss during dialysis and frequent blood sampling contribute to the decreased life span of erythrocytes in those on hemodialysis.4 The HbA1c is also lower due to the reduced red blood cell survival, red blood cell transfusions and erythropoietin treatments in those on hemodialysis.4,5,8,9 It is important to realize that erythropoietin accelerates the production of new erythrocytes and the proportion of young erythrocytes in peripheral blood must increase after erythropoietin injection.5
Additionally, these immature red blood cells have less glycemic exposure time for glycosylation to occur.5,8 The HbA1c levels are also theoretically suppressed by the resulting anemia associated with the shorter life span of erythrocytes. These factors establish the argument that HbA1c underestimates glycemic control in hemodialysis patients and that HbA1c is not a reliable test. Therefore, one should not use HbA1c as a guideline in patients with diabetes and renal disease who are on dialysis.3,4
Uzu and colleagues stated that HbA1c levels are underestimated in hemodialysis patients, especially in correlation with low hematocrit and those treated with higher doses of erythropoietin.4 The study recommended a more accurate means to estimate glycemic control:
• HbA1c x 1.14 if the hematocrit is ≥ 30%;
• HbA1c x 1.19 if the hematocrit is < 30% and treated with low dosages of erythropoietin; and
• HbA1c x 1.38 if hematocrit is < 30% and treated with high dosing of erythropoietin.
In those undergoing maintenance hemodialysis, researchers have reported that higher HbA1c values are incrementally associated with a higher burden of microvascular complications and a higher risk of cardiovascular death.4 Fukuoka and co-workers found no significant association between HbA1c and survival in diabetic ESRD patients.8 Evaluating patients from a large national dialysis organization, Kalantar-Zadeh and colleagues found a higher mortality rate in those with lower HbA1c levels.3
Can Glycated Albumin Be An Alternative Marker For Glycemic Control In Patients With Diabetes?
The lack of reliability in the HbA1c value in patients with diabetes and renal disease has prompted many questions and stimulated further research in this area. Serum glycated albumin (GA) is now under investigation and researchers have hypothesized it to be an alternative marker for glycemic control in patients with diabetes, including those with ESRD.5,8
Unlike HbA1c, which provides an integrated measure of plasma glucose over the past 120 days, mirroring the life span of an erythrocyte, GA is a glycemic indicator of the immediately previous two weeks. Glycated albumin is not affected by changes in the survival time of erythrocytes or changes in albumin concentration.5 Additionally, GA is not influenced by erythropoietin therapy.8 This is measured enzymatically via a liquid chemistry system and calculated as the percentage of GA relative to total serum albumin.4,5 This percentage is reportedly an accurate reflection of glycemic control. Therefore, one should consider the percentage of GA a more useful marker than HbA1c for determining glycemic control in patients with diabetes on hemodialysis.4