Development of features of glomerulopathy in tumor-bearing rats: a potential model for paraneoplastic glomerulopathy.
BACKGROUND
It has been well-recognized that cancer patients occasionally develop renal disorders independently of direct tumor invasion. However, the clinical entity of paraneoplastic glomerulopathy remains poorly understood, in part due to the lack of an animal model for basic research. In the present study, we investigated whether cancer-bearing rats develop features of glomerulopathy.


METHODS
RCN-9 rat colon cancer cells (1 × 10(7)) were injected into F344 rats (n = 13) and T cell-deficient F344 rats (nude rats; n = 7) via the portal system. Urinalysis and histological examinations were performed in comparison with control rats (n = 6) that received a vehicle injection.


RESULTS
Metastatic growth of RCN-9 cells exclusively in the liver was observed in the cancer-injected F344 rats, whereas direct invasion into the kidney was not evident even microscopically. Two of the cancer-injected F344 rats died within 2 days, but 9 of the 11 that avoided early death showed elevation of urinary protein (up to 158.0 mg/day) compared to controls (mean values: 60.8 ± 12.9 versus 17.8 ± 2.1 mg/day, P = 0.0291). Although morphological changes were not evident in light microscopy, abundant IgG in the glomerular tufts of the proteinuric rats was shown immunohistochemically. Ultrastructure analysis revealed electron-dense deposits in the glomerular basement membrane zone and effacement of the podocytic foot process. Interestingly, none of the nude rats showed proteinuria despite of cancer growth, suggesting that a specific immune response was involved.


CONCLUSIONS
The tumor-bearing rats developed features of glomerulopathy, as expected from the clinical perspective, and this animal model may provide new insights into the development of paraneoplastic glomerulopathies.
Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan. takeshin@jichi.ac.jp
Shin-ichi
S
Takeda
Junko
J
Chinda
Takashi
T
Murakami
Akihiko
A
Numata
Yoshitaka
Y
Iwazu
Tetsu
T
Akimoto
Yoshitomo
Y
Hamano
Shigeaki
S
Muto
Masafumi
M
Takahashi
Eiji
E
Kusano
D000230:Adenocarcinoma / Q000150:complications* / Q000556:secondary; D000818:Animals; D002452:Cell Count; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D050533:Glomerular Basement Membrane / Q000473:pathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications* / Q000556:secondary; D008297:Male; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude