Competition between albumin and low-molecular-weight proteins for renal tubular uptake in experimental nephropathies.
A controversy presently exists concerning the ability of albumin to inhibit the tubular reabsorption of low-molecular-weight (M(r)) proteins in experimental renal diseases leading to massive proteinuria. We have examined the urinary excretion of albumin and of 2 low-M(r) proteins, beta 2-microglobulin and cystatin C, in rats treated with toxins affecting primarily the glomerulus (puromycin amino-nucleoside and Adriamycin) or the tubule (mercuric chloride and maleic acid). Above a threshold of 100 mg/24 h, albuminuria induced by puromycin aminonucleoside (50 mg/kg) and Adriamycin (5 mg/kg) was associated with a marked increase in the urinary excretion of beta 2-microglobulin and cystatin C peaking at more than 100-fold the baseline levels. These glomerulotoxins did not affect the urinary excretion of the tubular enzyme N-acetyl-beta-D-glucosaminidase. This pattern of effects was completely different from that induced by mercuric chloride (2 mg/kg) and maleic acid (400 mg/kg) which increased the excretion of both N-acetyl-beta-D-glucosaminidase and low-M(r) proteins in rats with albuminuria values below 100 mg/24 h. These results strongly support the hypothesis that at high filtered loads, albumin decreases the tubular uptake of low-M(r) proteins most likely by competition for a common transport mechanism.
Unit of Industrial Toxicology and Occupational Medicine, Catholic University of Louvain, Brussels, Belgium.
N
N
Thielemans
R
R
Lauwerys
A
A
Bernard
D000118:Acetylglucosaminidase / Q000378:metabolism; D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001693:Biological Transport, Active; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000633:toxicity; D008627:Mercuric Chloride / Q000633:toxicity; D008970:Molecular Weight; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D001613:beta 2-Microglobulin / Q000378:metabolism
D000418:Albumins; C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D008298:Maleates; D011506:Proteins; D001613:beta 2-Microglobulin; D008627:Mercuric Chloride; D011692:Puromycin Aminonucleoside; D004317:Doxorubicin; C030272:maleic acid; D000118:Acetylglucosaminidase