High prevalence of immuno-unreactive intact albumin in urine of diabetic patients

Am J Kidney Dis. 2003 Feb;41(2):336-42. doi: 10.1053/ajkd.2003.50041.


Background: Intact albumin in urine may exist in two forms, immunoreactive and immuno-unreactive. Previous estimates of albuminuria in diabetic urine have only detected immunoreactive forms.

Methods: High performance liquid chromatography (HPLC) was used in this study to measure both forms of intact albumin (termed total intact albumin) to provide a more accurate measurement of albuminuria compared with radioimmunoassay (RIA) on 97 fresh urine samples from patients with diabetes. Eighty-six control urine samples from volunteers without diabetes were also tested.

Results: There was no significant difference between the two methods for nondiabetic controls. For diabetic urine samples, 91.6% of samples showed a greater concentration of albumin measured by HPLC than RIA. For normoalbuminuric diabetic samples, HPLC gave a mean albumin excretion rate of 12.5 +/- 4.4 microgram/min (SD), whereas RIA gave a rate of 8.0 +/- 6.7 microgram/min (P = 0.004; N = 28). For microalbuminuric samples, there also was a statistically significant difference: HPLC albumin excretion rate, 82.0 +/- 49.9 microgram/min, and RIA, 49.0 +/- 34.6 microgram/min (P = 0.004; N = 30). Thirty-two urine samples were normoalbuminuric by RIA (albumin, 11.4 +/- 3.9 microgram/min), but in the microalbuminuric range as determined by HPLC (albumin, 38.5 +/- 14.4 microgram/min). For urine samples in the macroalbuminuric range, there was no statistically significant difference between HPLC and RIA. Immuno-unreactive albumin was confirmed as albumin, analyzed by two-dimensional electrophoresis and matrix-assisted laser desorption ionization mass spectrometry.

Conclusion: These studies show that to determine microalbuminuria accurately, there is a need to assess urinary total intact albumin, rather than simply immunoreactive albumin. Am J Kidney Dis 41:336-342.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Albumins / analysis
  • Albumins / immunology*
  • Albuminuria / epidemiology*
  • Chromatography, High Pressure Liquid / methods
  • Diabetes Mellitus, Type 1 / urine*
  • Diabetes Mellitus, Type 2 / urine*
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Radioimmunoassay / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods


  • Albumins