Sci Adv
Lubiprostone preserves eGFR in patients with advanced CKD
Lubiprostone may be a safe therapeutic option to mitigate renal decline in CKD, acting via mitochondrial and polyamine pathways rather than uremic toxin reduction.
Study details: This multicenter, phase 2, randomized, double-blind, placebo-controlled trial enrolled 150 patients with stage IIIb-IV CKD across 9 Japanese centers. Participants received lubiprostone (8 or 16 μg) or placebo for 24 weeks. Primary endpoint was change in indoxyl sulfate; secondary endpoints included other uremic toxins, renal function markers, and safety.
Results: Lubiprostone didn't significantly alter uremic toxin levels. However, the 16-μg group demonstrated improved or preserved estimated glomerular filtration rate (eGFR) and eGFR slope. Mild-to-moderate GI events were reported in both placebo and high-dose groups. Multiomics analysis revealed modulation of the gut microbial agmatine pathway and increased spermidine, correlating with improved renal mitochondrial function.
Source:
Watanabe S, et al; LUBI-CKD TRIAL Investigators. (2025, August 29). Sci Adv. Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial. https://pubmed.ncbi.nlm.nih.gov/40880481/