Chronic administration of SMP-534 ameliorates renal dysfunction in 5/6 nephrectomized rats.
OBJECTIVE
Chronic kidney disease (CKD) is the common cause of end-stage renal disease. Antihypertensive agents are clinically used to inhibit the progression of CKD. However, these agents cannot completely prevent progression to renal failure. We have previously reported that 5-chloro-2-{(1E)-3-[2-(4-methoxybenzoyl)-4-methyl-1H- pyrrol-1-yl]prop-1en-1-yl}-N-(methylsulfonyl)benzamide (SMP-534) improves renal disease and prevents the production of extracellular matrix in vitro. Additionally, SMP-534 inhibits glomerular fibrosis and provides renoprotection in vivo. In the present study, we investigated the effect of SMP-534 on renal dysfunction in a 5/6 nephrectomized (5/6Nx) rat model.


METHODS
Five groups of rats were studied: sham operated, 5/6Nx + vehicle, 5/6Nx + SMP-534 30 mg/kg, 5/6Nx + SMP-534 60 mg/kg and 5/6Nx + SMP-534 90 mg/kg. Treatment with SMP-534 began 13 weeks after surgery, when hypertension and renal insufficiency had developed. Serum creatinine, blood urea nitrogen levels, creatinine clearance and urinary albumin were measured at specific time points.


RESULTS
Serum creatinine and blood urea nitrogen levels were significantly reduced in SMP-534-treated groups. In addition, SMP-534 dose-dependently suppressed the increase in urinary albumin excretion observed in 5/6Nx rats. Moreover, survival rates were improved in SMP-534-treated groups.


CONCLUSIONS
We have shown in this study that chronic oral administration of SMP-534 improves renal dysfunction in 5/6Nx rats. These findings indicate that SMP-534 may be a new therapeutic agent for the treatment of CKD.
Tsujimura
Tsuyoshi
T
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Drug Research Division, Osaka, Japan.
Nagamine
Jun
J
Sugaru
Eiji
E
Nakagawa
Tsutomu
T
Ono-Kishino
Michiko
M
Tokunaga
Teruhisa
T
Kitoh
Makoto
M
Nagata
Ryu
R
Taiji
Mutsuo
M
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D009392:Nephrectomy / Q000379:methods; D051381:Rats; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D001549:Benzamides; C505358:SMP-534