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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
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Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Chronic kidney disease (CKD) progression is a major global health burden, and novel therapeutic strategies are urgently needed. Constipation is associated with accelerated CKD progression, yet the renoprotective mechanisms of laxatives remain poorly defined. We conducted a clinical trial in patients with CKD to evaluate the effects of lubiprostone, a chloride-channel activator, on renal function and to investigate underlying mechanisms, with a particular focus on interactions between the gut microbiome and host pathways.
This Phase II, multicenter, randomized, double-blind, placebo-controlled trial enrolled 118 patients in Japan with moderate-to-severe CKD (eGFR 25-45 ml/min/1.73m²). Patients were randomized to receive placebo, 8 µg, or 16 µg of lubiprostone daily for 24 weeks. While the primary endpoint was the change in serum indoxyl sulfate, uremic toxin derived from intestinal bacteria, secondary endpoints included other uremic toxins and markers of renal function (e.g., eGFR). In addition, we conducted an exploratory multi-omics substudy (n=46), analyzing blood, urine and stool by capillary electrophoresis–time-of-flight mass spectrometry (CE-TOFMS) metabolomics and stool by shotgun metagenomics to explore mechanisms potentially mediating lubiprostone’s renoprotective effects.
Lubiprostone did not significantly change serum indoxyl sulfate or other major uremic toxins. However, the 16-µg group showed better preservation of renal function. Over 24 weeks, the least-squares mean change in eGFR was +0.37 mL/min/1.73 m² (95% CI, −0.70 to 1.44) with lubiprostone versus −1.55 mL/min/1.73 m² (95% CI, −2.83 to −0.27) with placebo (p=0.0457). The effect appeared more marked among patients with moderate CKD (eGFR 35–45 mL/min/1.73 m²) in exploratory subgroup analyses.
Diarrhea occurred in 14% of patients receiving lubiprostone; however, only one participant discontinued because of diarrhea. Overall discontinuation rates were 2 patients (5.7%) with placebo, 0 with 8 µg, and 4 (8%) with 16 µg, indicating no clear between-group difference in safety.
To probe this renoprotective signal, the exploratory multi-omics substudy indicated that lubiprostone modulated the gut microbiome, with an increased relative abundance of the fecal aguA (agmatine deiminase) gene and elevated circulating spermidine in plasma. In complementary in vivo and in vitro studies, exogenous spermidine administration improved renal mitochondrial function and mitigated renal dysfunction, consistent with a mechanistic link (without direct measurement of systemic levels).
Lubiprostone attenuated the decline in renal function over 24 weeks in patients with CKD, despite no measurable reductions in major uremic toxins, and was generally well tolerated. Exploratory multi-omics and validation studies support a hypothesis in which gut microbiome modulation increases systemic polyamine exposure, thereby enhancing renal mitochondrial function along a gut–polyamine–mitochondria axis. Targeting this pathway may represent a promising strategy for CKD. Findings were published in August 2025 in Science Advances. Clinical Trials Registry Number: UMIN000023850.
