Immuno-unreactive albumin excretion increases in streptozotocin diabetic rats

Kerryn A. Greive, Gabriela A. Eppel, Shane Reeve, A. Ian Smith, George Jerums, Wayne D. Comper

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Abstract

We previously showed that albumin is fragmented (>90%) during renal passage to low-molecular-weight (<10 kd) peptides. The aim of the present study was to document the renal handling of albumin in experimental diabetes. Tritium-labeled albumin was infused into control and streptozotocin (STZ) diabetic rats during 7 days. Urinary radioactivity, assessed by size exclusion chromatography, revealed a major peak corresponding to low-molecular-weight, albumin-derived fragments and a minor peak corresponding to intact albumin or high-molecular-weight, albumin-derived protein. The fractional clearance of albumin, calculated from total radioactivity measurements, was at least 100-fold greater than the fractional clearance of albumin determined by radioimmunoassay (RIA) for control and diabetic rats. This result was mainly because low-molecular-weight, albumin-derived fragments were not detected by RIA. The fractional clearance of high-molecular-weight, albumin-derived protein was 2- to 10-fold greater than the fractional clearance determined by RIA. The immuno-unreactive high-molecular-weight, albumin-derived protein (called ghost albumin), characterized by size exclusion chromatography and high-performance liquid chromatography, was present in control and diabetic rat urine. Ghost albumin excretion rate was enhanced 11-fold after 8 weeks of STZ diabetes as compared with aged-matched controls. This study shows that renal modification resulting in low-molecular-weight and high-molecular-weight components of albumin is a major contributor to the renal handling of albumin. The results indicate that excretion of modified albumin is increased in STZ rats as compared with albumin detected by conventional RIA. Long-term studies are necessary to evaluate the potential of ghost albumin as a new marker for the assessment of urinary albumin in diabetes.

Original languageEnglish
Pages (from-to)144-152
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume38
Issue number1
DOIs
Publication statusPublished - 1 Jan 2001

Keywords

  • Albumin degradation
  • Albuminuria
  • Intact albumin
  • Lysosome
  • Radioimmunoassay (RIA)

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