A medicine commonly used to treat constipation may have an unexpected benefit for people with chronic kidney disease. Researchers in Japan found that the drug lubiprostone may help slow the loss of kidney function.
Chronic kidney disease, or CKD, happens when the kidneys gradually lose their ability to work properly. The kidneys normally remove waste and extra fluid from the blood while helping control blood pressure and maintaining the right balance of important substances in the body.
Kidney damage can become worse over many years without causing obvious symptoms at first. In advanced cases, patients may eventually need dialysis, a treatment that removes waste and extra fluid from the blood when the kidneys can no longer do enough of this work.
Modern treatments can already help many people slow the progression of CKD and reduce complications. However, kidney damage can still continue despite treatment, so scientists are searching for additional ways to preserve kidney function for longer.
A research team led by Professor Takaaki Abe at Tohoku University Graduate School of Medicine investigated a surprising possibility. They studied lubiprostone, a medicine normally prescribed to help people who have chronic constipation.
The idea came partly from an observation about people with kidney disease. Constipation is common among CKD patients, and scientists increasingly believe that the health of the intestines may be connected to kidney health.
The human gut contains trillions of bacteria and other tiny organisms. Together, they form a complex community that helps digest food and produces substances that can travel through the body and influence other organs.
When this community becomes unbalanced, it may increase inflammation or produce substances that place additional stress on the kidneys. Researchers therefore wondered whether improving the gut environment could also help protect kidney function.
To investigate, the scientists conducted a Phase II clinical trial called the LUBI-CKD TRIAL. It involved 150 people with moderate chronic kidney disease at nine medical centers in Japan.
Participants were randomly given either a placebo, which contained no active drug, or different doses of lubiprostone. Researchers then monitored their kidney function using a measurement called estimated glomerular filtration rate, or eGFR.
eGFR is commonly used by doctors to estimate how effectively the kidneys are filtering the blood. A falling eGFR can be a sign that kidney disease is becoming worse.
The researchers found that kidney function declined more slowly in people receiving lubiprostone than in those receiving the placebo. Higher doses were associated with a stronger effect, providing encouraging evidence that the medicine could influence the progression of the disease.
The scientists also investigated why a constipation medicine might affect the kidneys. Their results pointed toward changes involving the bacteria living in the gut and a natural substance called spermidine.
Lubiprostone appeared to increase the production of spermidine and encourage changes in gut bacteria. These changes were linked to better function of the tiny structures inside cells that produce most of their energy.
Improving this cellular energy system could help kidney cells remain healthier and better able to withstand damage. The findings add to growing evidence that the gut and kidneys communicate with each other in important ways.
However, the results do not mean that people with CKD should start taking lubiprostone specifically to protect their kidneys. This was a Phase II trial involving 150 patients, and larger studies are needed to confirm that the treatment is both effective and safe for wider use.
The researchers are now planning a larger Phase III clinical trial. They also hope to identify signs that could help doctors predict which patients are most likely to benefit from the treatment.
If future studies confirm the findings, lubiprostone could eventually provide doctors with another way to slow kidney disease and potentially delay serious complications. It may also strengthen the idea that protecting the gut could become an important part of treating diseases elsewhere in the body.
The research led by Professor Takaaki Abe at Tohoku University Graduate School of Medicine was published in the journal Science Advances.
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