便秘薬に慢性腎臓病（CKD）の進行抑制効果がある

既存の便秘症治療薬に慢性腎臓病（CKD）の進行抑制効果があることが、東北大学大学院の阿部高明教授らの検討で明らかになった。慶應義塾大学との共同研究結果で、同薬がCKDの新しい治療薬になる可能性が期待されるという。

　「Journal of the American Society of Nephrology」電子版に2014年12月18日掲載された論文によると、検討では慢性腎不全のマウスにルビプロストンという便秘治療薬を投与し、効果を検証した。

　その結果、投与マウスでは腸液の分泌が増加し、腸壁の悪化が改善されていた。腸内細菌叢も善玉菌の減少が改善していた。腸内環境の改善に伴って体内への尿毒素の蓄積も軽減され、結果として腎障害の進行が抑えられた。

　CKDは糖尿病や高血圧に多く合併するが、現在のところ原疾患の治療以外に進行を抑制する方法はない。

Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD.

Eikan Mishima, Shinji Fukuda, Hisato Shima, Akiyoshi Hirayama, Yasutoshi Akiyama, Yoichi Takeuchi, Noriko N Fukuda, Takehiro Suzuki, Chitose Suzuki, Akinori Yuri, Koichi Kikuchi, Yoshihisa Tomioka, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

Journal of the American Society of Nephrology : JASN. 2014 Dec 18; pii: ASN.2014060530.

PMID:25525179

Abstract

The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis-mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment.