Combination therapy with SMP-534 and an angiotensin-converting enzyme inhibitor provides additional renoprotection in 5/6 nephrectomized rats.
The number of patients with chronic kidney disease (CKD) has continuously grown worldwide. Treatment with antihypertensive agents reduces the rate of progression of CKD, however, there is still a large unmet need to develop strategies for the treatment of CKD. Although we have previously reported that the antifibrotic agent, SMP-534 inhibits the progression of CKD, it is unknown whether combination therapy with SMP-534 and antihypertensive agent shows additive effects on CKD. In present study, we examined whether combination therapy with SMP-534 and the antihypertensive agent, lisinopril is more effective than single therapy with SMP-534 or lisinopril on five-sixths nephrectomized (5/6Nx) rat model. Combination therapy with SMP-534 (50 mg/kg) and lisinopril (5 mg/kg) significantly decreased urinary albumin excretion, blood urea nitrogen (BUN) and serum creatinine and increased creatinine clearance in 5/6Nx rats. On the other hands, single treatment with SMP-534 or lisinopril did not improve renal function at this dose. In addition, combination therapy with SMP-534 and lisinopril significantly decreased extracellular matrix (ECM) accumulation in renal glomeruli and tubulointerstitial injury. These data suggest that combination therapy with an antifibrotic agent and an antihypertensive agent may offer a new therapeutic option for suppressing the progression of CKD.
Tsujimura
Tsuyoshi
T
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd.
Nagamine
Jun
J
Sugaru
Eiji
E
Ono-Kishino
Michiko
M
Tokunaga
Teruhisa
T
Kitoh
Makoto
M
Nagata
Ryu
R
Nakagawa
Tsutomu
T
Taiji
Mutsuo
M
D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005109:Extracellular Matrix / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009392:Nephrectomy; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001549:Benzamides; D020011:Protective Agents; C505358:SMP-534; D003404:Creatinine; D017706:Lisinopril