Glycohaemoglobin measurement: methodological differences in relation to interference by urea

Acta Diabetol. 2002 Apr;39(1):35-9. doi: 10.1007/s005920200010.


The aim of this study was to investigate the agreement between a cation-exchange HPLC method and a boronate affinity method of measuring glycohaemoglobin (HbA1c), with particular reference to the effect of elevated urea concentration. HbA1c was measured by both methods in samples from 75 subjects who were classified as diabetic with normal (n=36) or abnormal (n=12) renal function, and non-diabetic with normal (n=8) or abnormal (n=19) renal function. Urea was found to cause a clinically significant interference in the HPLC method at a level > or =17.0 mmol/l. Each increase of 1 mmol/l urea in serum was associated with an absolute increase of 0.04% in the HbA1c value as measured by the HPLC method. The boronate affinity method for HbA1c did not appear to be affected by elevated urea concentration. There was significant correlation (r=0.97, p<0.001) between HbA1c results obtained by the two methods, however, results obtained by the boronate affinity method were generally lower. The discrepancy between results obtained by the two methods was particularly marked in uraemic samples from diabetic subjects, as the HPLC/boronate affinity difference increased as the HbA1c increased and also as the urea concentration increased. Results indicate that blood from diabetic patients with renal failure may give erroneously high HbA1c values by HPLC. Results also highlight the importance of choosing appropriate clinical samples and statistical techniques when evaluating or comparing test methods.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Affinity
  • Chromatography, High Pressure Liquid
  • Diabetes Mellitus / blood*
  • Diabetic Nephropathies / blood
  • Glycated Hemoglobin A / analysis*
  • Glycated Hemoglobin A / isolation & purification
  • Humans
  • Kidney Diseases / blood
  • Reference Values
  • Regression Analysis
  • Reproducibility of Results
  • Urea / blood*


  • Glycated Hemoglobin A
  • Urea