Degradation of albumin by the renal proximal tubule cells and the subsequent fate of its fragments.
BACKGROUND
In view of recent reports of large amounts of albumin fragments present in normal urine we investigated the mechanism of albumin handling by the proximal tubule.


METHODS
We injected (125)I-albumin intravenously in rats and measured the excretion of intact and degraded (125)I-albumin in the urine by trichloroacetic acid (TCA) precipitation. The excretion rate of intact (125)I-albumin was compared to that obtained by routine radioimmunoassay (RIA). Human proximal tubular HK-2 cells were used to characterize the albumin receptor and study the degradation of albumin to peptides, establish their size by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration chromatography, and determine the direction in which the degradation products are removed from the cell.


RESULTS
Following injection of (125)I-albumin intravenously into rats we recovered large quantities of (125)I-albumin fragments in urine and determined that 98% was in a highly degraded form and only 2% was intact. Only the intact albumin could be detected by RIA. We observed similar results in the urine of ex vivo kidneys perfused with (125)I-albumin. We found that (125)I-albumin was taken up by HK-2 cells via a receptor, degraded in the lysosomes and the peptides exocytosed to both the apical and basolateral sides of the cells.


CONCLUSIONS
We conclude that normally the kidney degrades large amounts of albumin and that the degradation fragments appear in the urine. These findings are in sharp contrast with the established view that degraded albumin is completely reabsorbed into the blood stream.
Gudehithlu
Krishnamurthy P
KP
Division of Nephrology, Cook County Hospital, Section of Nephrology, University of Illinois at Chicago, and VAMC, West Side Division, USA.
Pegoraro
Alfredo A
AA
Dunea
George
G
Arruda
Jose A L
JA
Singh
Ashok K
AK
D000818:Animals; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004705:Endocytosis; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000008:administration & dosage / Q000378:metabolism*
D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D012709:Serum Albumin; D002738:Chloroquine