Renal tubular lesions induced by human Bence Jones protein in the rat: N-acetyl-beta-D-glucosaminidase as a sensitive marker.
The renal tubular lesion induced by human Bence Jones proteins (BJPs) in the rat was investigated to elucidate the initial role of BJPs in the genesis of renal tubular damage in myeloma kidney. Human BJP extracted from the urine collected from a patient with lambda light chain myeloma was given intraperitoneally to Sprague-Dawley rats with a daily dose of 300 mg/day for 5 days (BJP group, n = 16). Daily urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), which may represent the intensity of tubular damage, was measured. On days 10 and 20 after start of the injection, the kidneys were removed and examined by light and electron microscopy. The renal content of NAG was also measured to estimate the lysosomal activity. Both urinary and renal tissue NAG were significantly higher in the BJP group than in control rats injected with bovine serum albumin (n = 16). The most characteristic changes were found in the proximal tubules of the BJP group; the number and size of lysosomes were increased, and some showed enlargement with autophagic vacuolation. However, these were not found in the control group. There were no obvious changes in the distal tubules in either group, and the glomeruli appeared to be intact. These results suggest that BJP directly damages the proximal tubules via the process of catabolism, resulting in injury to these cells, and that the urinary NAG is a sensitive marker to detect early tubular damage by BJP.
Yokota
N
N
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Yamamoto
Y
Y
Kitamura
K
K
Kuroki
N
N
Hisanaga
S
S
Fujimoto
S
S
Eto
T
T
Tanaka
K
K
D000118:Acetylglucosaminidase / Q000032:analysis / Q000652:urine*; D000818:Animals; D001536:Bence Jones Protein / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis / Q000652:urine; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009101:Multiple Myeloma / Q000473:pathology; D009194:Myeloma Proteins / Q000633:toxicity*; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000633:toxicity
D015415:Biomarkers; D009194:Myeloma Proteins; D012710:Serum Albumin, Bovine; D001536:Bence Jones Protein; D000118:Acetylglucosaminidase