Immuno-unreactive albumin excretion increases in streptozotocin diabetic rats.
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.
Greive
K A
KA
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Eppel
G A
GA
Reeve
S
S
Smith
A I
AI
Jerums
G
G
Comper
W D
WD
D000418:Albumins / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000652:urine; D005919:Glomerular Filtration Rate; D007260:Infusion Pumps; D008297:Male; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014316:Tritium; D014563:Urodynamics
D000418:Albumins; D010446:Peptide Fragments; D014316:Tritium