A constipation drug has shown promise in slowing kidney damage in chronic kidney disease patients by improving gut and mitochondrial health.
Chronic kidney disease (CKD) is a widespread and serious medical condition. For many individuals, the progressive loss of kidney function ultimately requires regular dialysis to prevent kidney failure and sustain life. Although CKD poses a major global health challenge, no drug has yet been approved that can directly enhance kidney performance.
A team led by Professor Takaaki Abe at Tohoku University Graduate School of Medicine has uncovered a surprising possibility. They tested a medication normally prescribed for constipation and found that it may help protect kidney health. For the first time, this drug (lubiprostone) demonstrated an ability to slow the decline of kidney function in patients with CKD.
“We noticed that constipation is a symptom that often accompanies CKD, and decided to investigate this link further,” explains Abe. “Essentially, constipation disrupts the intestinal microbiota, which worsens kidney function. Working backwards, we hypothesized that we could improve kidney function by treating constipation.”
To explore this idea, the researchers launched a multicenter Phase II clinical trial (LUBI-CKD TRIAL) at nine medical institutions in Japan. The study involved 150 patients with moderate CKD and carefully assessed how lubiprostone influenced their kidney function.
Clinical Trial Results
The results showed that, compared to the placebo group, the decline in kidney function (defined as the estimated glomerular filtration rate: eGFR) was suppressed in a dose-dependent manner in patients treated with 8 µg or 16 µg of lubiprostone.
The researchers also investigated the mechanism underlying how this effect occurred. They found that lubiprostone increases spermidine production, which improves mitochondrial function by promoting bacterial growth in the gut. The improved mitochondrial function was seen to exert a renoprotective effect – suppressing further kidney damage.
Going forward, the research team has plans to validate the trial results in a larger population (Phase 3 clinical trial) and advance the exploration of biomarkers that predict treatment efficacy. Their goal is to provide each patient with CKD the optimal treatment plan tailored to their needs. This discovery has the potential to significantly transform the conventional approach to CKD treatment, which primarily focuses on reducing uremic toxins.
These findings suggest a new therapeutic strategy in which laxatives suppress renal function decline. This strategy is expected to contribute to the development of treatments for not only CKD, but also mitochondrial dysfunction disorders.
Reference: “Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial” by Shun Watanabe, Masaaki Nakayama, Takashi Yokoo, Satoru Sanada, Yoshifumi Ubara, Atsushi Komatsuda, Katsuhiko Asanuma, Yusuke Suzuki, Tsuneo Konta, Junichiro J. Kazama, Takehiro Suzuki, Shinji Fukuda, Tomoyoshi Soga, Takuji Yamada, Sayaka Mizutani, Mitsuharu Matsumoto, Yuji Naito, Kensei Taguchi, Kei Fukami, Hitomi Kashiwagi, Koichi Kikuchi, Chitose Suzuki, Hidetaka Tokuno, Marina Urasato, Ryota Kujirai, Yotaro Matsumoto, Yasutoshi Akiyama, Yoshihisa Tomioka, Shun Itai, Yoshiyasu Tongu, Eikan Mishima, Chiharu Kawabe, Tomoko Kasahara, Yoshiaki Ogata, Takafumi Toyohara, Takeya Sato, Tetsuhiro Tanaka, Takaaki Abe and LUBI-CKD TRIAL Investigators, 29 August 2025, Science Advances.
DOI: 10.1126/sciadv.adw3934
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