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Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model

Yuki Narita, Miki Ueda, Kohei Uchimura, Yutaka Kakizoe, Yoshikazu Miyasato, Teruhiko Mizumoto, Jun Morinaga, Manabu Hayata, Terumasa Nakagawa, Masataka Adachi, Taku Miyoshi, Yoshiki Sakai (+4 others)
2016 Journal of Pharmacological Sciences  

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We previously reported that camostat mesilate (CM) had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE), a renin-angiotensin-aldosterone system (RAS) inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day) and/or TE (10 mg/kg/day) on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks
more » ... t period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.
doi:10.1016/j.jphs.2016.01.003 pmid:26887332 fatcat:wjxxyrp7ozc2lmt6plzclwim5a
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Yuki Narita, Miki Ueda, Kohei Uchimura, Yutaka Kakizoe, Yoshikazu Miyasato, Teruhiko Mizumoto, Jun Morinaga, Manabu Hayata, Terumasa Nakagawa, Masataka Adachi, Taku Miyoshi, Yoshiki Sakai, Daisuke Kadowaki, Sumio Hirata, Masashi Mukoyama, Kenichiro Kitamura. "Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model." Journal of Pharmacological Sciences 130.2 (2016) 110-116