Gut Health to Kidney Health: Constipation Drug Lubiprostone Halts Kidney Decline

 

​A groundbreaking study, led by Professor Takaaki Abe at the Tohoku University Graduate School of Medicine in Japan, has uncovered an unexpected therapeutic use for a common constipation medication, lubiprostone, in managing Chronic Kidney Disease (CKD). The findings suggest that this drug can significantly slow the loss of kidney function in CKD patients, opening a promising new avenue for treatment centered around the gut.

​The Gut-Kidney Connection

​The research began by observing a correlation between constipation and the worsening of kidney function in CKD patients. The hypothesis was that constipation disrupts the intestinal microbiota (gut bacteria), which, in turn, exacerbates the damage to the kidneys.

​The researchers reasoned that by treating the constipation and restoring balance to the gut environment, they could indirectly improve kidney health. This led them to test the constipation drug lubiprostone.

​Clinical Evidence for Kidney Protection

​The team conducted a multicenter Phase II clinical study (LUBI-CKD TRIAL) involving 150 individuals with moderate CKD in Japan. The results demonstrated a clear protective effect:

​Slower Decline in Kidney Function: Participants who received lubiprostone (at 8 ug or 16 ug doses) experienced a slower decline in their estimated glomerular filtration rate (eGFR) compared to those on a placebo. The eGFR is the standard measure used by doctors to assess how well the kidneys are filtering waste.

​This finding marks the first time a common constipation drug has been shown in a clinical trial to actively preserve kidney function in people with CKD.

​The Mechanism of Action: Boosting Mitochondria

​The scientists went on to explore why lubiprostone had this renoprotective effect, uncovering a complex link involving gut bacteria and cellular energy production:

​Spermidine Production: Lubiprostone was found to encourage the growth of beneficial gut bacteria.

​Mitochondrial Enhancement: These bacteria then boost the production of spermidine, a compound known to enhance mitochondrial activity. 3. Renoprotective Effect: Improved mitochondrial function in the kidney cells was directly linked to a renoprotective effect, helping to limit further damage and slow the progression of the disease.

​Future Outlook for CKD Treatment

​These findings are highly significant because there are currently no approved medications that can actively restore kidney function; most therapies focus only on managing symptoms and lowering uremic toxins.

​The research points toward a gut-based, mitochondria-boosting therapy as a fundamentally new treatment strategy for CKD. The team plans to proceed with a Phase III clinical trial involving a larger group of participants and aims to identify biomarkers to personalize treatment, ensuring the right patients receive this potentially game-changing therapy.