Monoclonal antibody 1-22-3-induced glomerulonephritis in uninephrectomized rats as a model of progressive renal failure.
BACKGROUND
At present, there are few available animal models of progressive renal failure originating from mesangial proliferative glomerulonephritis (GN). In the current study, we examined the usefulness of anti-Thy-1 monoclonal antibody (mAb) 1-22-3-induced GN in uninephrectomized rats as a model of progressive renal failure by analysing the similarities to human disease.


METHODS
GN was induced by intravenous injection of mAb 1-22-3 into uninephrectomized male Wistar rats. The natural course of the disease was analysed in this model for 47 weeks. The effect of treatment with the angiotensin-converting enzyme inhibitor, captopril, on renal functional outcome was also examined in this model for 23 weeks, beginning from 1 week after antibody injection.


RESULTS
Injection of mAb 1-22-3 induced a persistent proteinuria during the entire study period. Animals showed a progressive decline in renal function and 63% died by week 47. Severe glomerular and tubulointerstitial lesions were consistently observed. Treatment with captopril significantly inhibited increases in proteinuria and blood pressure, and attenuated renal injury. Captopril also retarded the progression of renal failure, and decreased mortality. Finally, the level of proteinuria was significantly correlated with the rate of decline in renal function, and the reduction in proteinuria by captopril was accompanied by a slower progression of renal failure.


CONCLUSIONS
The mAb 1-22-3-induced GN in a uninephrectomized rat model simulates the clinical manifestations of human disease, indicating that this model may be useful for studying progressive renal failure and for investigating new therapeutic strategies against renal failure.
Tomita
Masayuki
M
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan. masayuki.tomita@jp.astellas.com
Sogabe
Hajime
H
Nakazato
Shoko
S
Nakatsuji
Shunji
S
Noto
Takahisa
T
Hamada
Kaori
K
Kawachi
Hiroshi
H
Shimizu
Fujio
F
Matsuo
Masahiko
M
Mutoh
Seitaro
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D001794:Blood Pressure / Q000502:physiology; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D018450:Disease Progression; D005500:Follow-Up Studies; D005920:Glomerular Mesangium / Q000648:ultrastructure; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D007518:Isoantibodies / Q000633:toxicity*; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000648:ultrastructure; D008297:Male; D009392:Nephrectomy; D010784:Photomicrography; D011507:Proteinuria / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D051381:Rats
D000911:Antibodies, Monoclonal; D007518:Isoantibodies; C035678:anti-Thy antibody; D003404:Creatinine