Chronic kidney disease (CKD) affects hundreds of millions of people worldwide and is one of the leading causes of kidney failure. As the disease progresses, many patients eventually need dialysis to survive. While current treatments can help slow damage, there are still no approved medications that directly restore kidney function.
Researchers at Tohoku University Graduate School of Medicine uncovered an unexpected possibility involving a drug that has long been used to treat constipation. In a clinical trial, the medication lubiprostone appeared to slow the decline of kidney function in patients with moderate CKD, raising hopes for an entirely new approach to kidney disease treatment.
"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."
The Surprising Gut Kidney Connection
Doctors have increasingly focused on what researchers call the "gut kidney axis," the complex relationship between intestinal bacteria and kidney health. People with CKD often experience constipation and imbalances in gut microbes, which can contribute to inflammation and the buildup of harmful compounds in the body.
Earlier research had hinted that improving gut health might help protect the kidneys, but evidence in humans remained limited. To explore the idea further, researchers launched the multicenter Phase II clinical trial known as the LUBI-CKD TRIAL across nine medical institutions in Japan.
The study enrolled 150 patients with moderate chronic kidney disease. Participants received either lubiprostone or a placebo, allowing scientists to compare how the treatment affected kidney function over time.
The results surprised the researchers. Patients who received either 8 µg or 16 µg doses of lubiprostone showed a slower decline in kidney function compared with those in the placebo group. Kidney performance was measured using estimated glomerular filtration rate (eGFR), one of the most widely used indicators of kidney health.
Researchers reported that the protective effect appeared dose dependent, meaning higher doses were linked to greater benefits. The 16 µg group showed particularly promising preservation of kidney function signals during the 24 week trial period.
How a Constipation Drug May Protect the Kidneys
Scientists then investigated why the drug appeared to help the kidneys.
Their analysis pointed to changes in the gut microbiome. Lubiprostone increased the production of spermidine, a naturally occurring compound tied to healthier mitochondrial activity. Mitochondria are often described as the power plants of cells because they generate the energy cells need to function properly.
The researchers found that improved mitochondrial function may help shield kidney tissue from further damage. They also identified changes in bacterial pathways connected to polyamine production, adding more evidence that gut microbes may directly influence kidney health.
Interestingly, the treatment did not significantly reduce certain uremic toxins that scientists originally expected to change. Instead, the kidney benefits seemed tied more closely to microbiome remodeling and mitochondrial support. That finding could reshape how researchers think about treating CKD in the future.
Why Researchers Are Excited About the Findings
The study has drawn attention because lubiprostone is already an approved medication for chronic constipation, potentially making future clinical use faster than developing a completely new drug from scratch.
Researchers also believe the discovery may have implications beyond kidney disease. Because mitochondrial dysfunction is involved in many chronic illnesses, scientists are exploring whether similar gut targeted approaches could eventually help other disorders as well.
The research team is now planning larger Phase 3 trials to confirm whether the benefits hold up in broader patient populations. Scientists are also searching for biomarkers that could predict which patients are most likely to respond to treatment.
Although more research is still needed, the findings have added momentum to a rapidly growing area of medicine focused on the connection between gut bacteria, cellular energy production, and chronic disease progression. For people living with CKD, even modest slowing of kidney decline could potentially delay dialysis and improve quality of life.
