Immuno-unreactive albumin excretion increases in streptozotocin diabetic rats

We previously showed that albumin is fragmented (> 90%) during renal passag e to low-molecular-weight (< 10 kd) peptides. The aim of the present study was to document the renal handling of albumin in experimental diabetes. Tri tium-labeled albumin was infused into control and streptozotocin (STZ) diab etic 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 albumi n or high-molecular-weight, albumin-derived protein. The fractional clearan ce of albumin, calculated from total radioactivity measurements, was at lea st 100-fold greater than the fractional clearance of albumin determined by radioimmunoassay (RIA) for control and diabetic rats. This result was mainl y 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 prote in (called ghost albumin), characterized by size exclusion chromatography a nd high-performance liquid chromatography, was present in control and diabe tic rat urine. Ghost albumin excretion rate was enhanced 11-fold after 8 we eks of STZ diabetes as compared with aged-matched controls. This study show s that renal modification resulting in low-molecular-weight and high-molecu lar-weight components of albumin is a major contributor to the renal handli ng of albumin. The results indicate that excretion of modified albumin is i ncreased 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. (C) 200 1 by the National Kidney Foundation, Inc.