Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model

Eikan Mishima, Shinji Fukuda, Yoshitomi Kanemitsu, Daisuke Saigusa, Chikahisa Mukawa, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Tatsuki Tachikawa, Tomoya Tsukimi, Noriko N. Fukuda, Hsin Jung Ho, Koichi Kikuchi, Chitose Suzuki, Fumika Nanto, Takehiro Suzuki, Sadayoshi Ito, Tomoyoshi Soga, Yoshihisa Tomioka, Takaaki Abe

研究成果: Article査読

28 被引用数 (Scopus)

抄録

Mishima E, Fukuda S, Kanemitsu Y, Saigusa D, Mukawa C, Asaji K, Matsumoto Y, Tsukamoto H, Tachikawa T, Tsukimi T, Fukuda NN, Ho HJ, Kikuchi K, Suzuki C, Nanto F, Suzuki T, Ito S, Soga T, Tomioka Y, Abe T. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. Am J Physiol Renal Physiol 315: F824–F833, 2018. First published November 22, 2017; doi:10.1152/ajprenal.00314.2017.—Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins, including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg po) treatment did not influence the impaired renal function; however, it significantly reduced the plasma levels of p-cresyl sulfate and indoxyl sulfate in renal failure mice (a 75% and 26% reduction, respectively, compared with the vehicle group). Additionally, canagliflozin significantly increased cecal short-chain fatty acids in the mice, suggesting the promotion of bacterial carbohydrate fermentation in the intestine. Analysis of the cecal microbiota showed that canagliflozin significantly altered microbiota composition in the renal failure mice. These results indicate that canagliflozin exerts intestinal effects that reduce the accumulation of uremic toxins including p-cresyl sulfate. Reduction of accumulated uremic toxins by canagliflozin could provide a potential therapeutic option in chronic kidney disease.

本文言語English
ページ(範囲)F824-F833
ジャーナルAmerican Journal of Physiology - Renal Physiology
315
4
DOI
出版ステータスPublished - 2018 10

ASJC Scopus subject areas

  • 生理学
  • 泌尿器学

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