“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 address this issue, the group conducted a multicenter Phase II clinical trial (LUBI-CKD TRIAL) at nine Japanese medical institutions, enrolling 150 patients with moderate CKD. This study evaluated the effects of lubiprostone on kidney function. 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. The results of this study were published in the scientific journal Science Advances on August 30, 2025.
Reference:
Shun Watanabe et al. ,Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial.Sci. Adv.11,eadw3934(2025).DOI:10.1126/sciadv.adw3934
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