Tag: chronic kidney disease

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Clinical Trial Shows a Constipation Drug Aids Kidney Function

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Human kidney. Credit: Scientific Animations CC0

Chronic kidney disease (CKD) is a major health issue worldwide. Many patients end up requiring regular dialysis to avoid kidney failure and stay alive. Despite the severity of the condition, there are currently no drugs available that improve kidney function. A research group led by Tohoku University Graduate School of Medicine’s Professor Takaaki Abe has found a remarkable solution to treat patients with CKD by co-opting a drug typically used for constipation. This is the first time that this drug (lubiprostone) was shown to prevent the decline of renal function in patients with CKD.

“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 hypothesised that we could improve kidney function by treating constipation.”

To address this issue, the group conducted a multicentre Phase II clinical trial (LUBI-CKD TRIAL) at nine Japanese medical institutions, enrolling 150 patients with moderate CKD. This study evaluated the effects of lubiprostone on kidney function. The results showed that, compared to the placebo group, the decline in kidney function (defined as the estimated glomerular filtration rate: eGFR) was suppressed in a dose-dependent manner in patients treated with 8µg or 16µg of lubiprostone.

The researchers also investigated the mechanism underlying how this effect occurred. They found that lubiprostone increases spermidine production, which improves mitochondrial function by promoting bacterial growth in the gut. The improved mitochondrial function was seen to exert a renoprotective effect – suppressing further kidney damage.

Going forward, the research team has plans to validate the trial results in a larger population (Phase 3 clinical trial) and advance the exploration of biomarkers that predict treatment efficacy. Their goal is to provide each patient with CKD the optimal treatment plan tailored to their needs. This discovery has the potential to significantly transform the conventional approach to CKD treatment, which primarily focuses on reducing uremic toxins.

These findings suggest a new therapeutic strategy in which laxatives suppress renal function decline. This strategy is expected to contribute to the development of treatments for not only CKD, but also mitochondrial dysfunction disorders. The results of this study were published in Science Advances on August 30, 2025.

Source: Tohoku University

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GLP-1 Receptor Agonists also Protect the Kidneys, Study Shows

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GLP-1 agonists significantly reduced kidney deterioration and failure, regardless of diabetes status

Chronic kidney disease (CKD). Credit: Scientific Animations CC4.0

The biggest and most comprehensive analysis of glucagon-like peptide-1 (GLP-1) receptor agonists on kidney and cardiovascular outcomes shows they have significant benefits in people with and without diabetes.1 Findings appear in The Lancet Diabetes & Endocrinology.

Originally developed to treat diabetes, GLP-1 receptor agonists mimic the action of glucagon-like peptide 1, a hormone which stimulates insulin production and lowers blood sugar levels. More recently, they have emerged as effective treatments for obesity – slowing digestion, increasing satiety and reducing hunger. 

But while the benefits of GLP-1 receptor agonists for the treatment of type 2 diabetes, obesity and cardiovascular disease are well known, their impact on chronic kidney disease (CKD) has been less certain.

Researchers conducted a meta-analysis of 11 large-scale clinical trials of GLP-1 receptor agonists involving a total of 85 373 people (79.4% with type 2 diabetes and 20.6% with overweight or obesity and cardiovascular disease but without diabetes). Seven different GLP-1 receptor agonists were investigated among the trials. 

The results showed that compared to placebo, GLP-1 receptor agonists reduced the risk of kidney failure by 16% and the worsening of kidney function by 22% (defined by a drop in estimated glomerular filtration rate – a measure of how much blood the kidneys filter clean every minute – of at least 50%). The combined reduction in the risk of kidney failure, worsening kidney function, and death due to kidney disease was 19%. 

The analysis also confirmed previous findings that GLP-1 receptor agonists protect cardiovascular health, with a 14% reduction in the risk of cardiovascular death, non-fatal heart attack, and non-fatal stroke, compared to placebo. Death by any cause was 13% lower among patients treated with GLP-1 receptor agonists.

Lead author Professor Sunil Badve, Professorial Fellow at The George Institute for Global Health and UNSW Sydney said the study expanded current knowledge about this class of drugs in key areas, including benefits in people with CKD, and in people with and without diabetes. 

“This is the first study to show a clear benefit of GLP-1 receptor agonists on kidney failure or end-stage kidney disease, suggesting they have a key role in kidney-protective and heart-protective treatment for patients with common medical conditions like type 2 diabetes, overweight or obesity with cardiovascular disease, or CKD,” he said.

“These results are particularly important for patients with chronic kidney disease. It is a progressive condition eventually leading to kidney failure requiring dialysis or kidney transplantation and is associated with premature death, mostly from heart disease. It has a significant impact on patients’ quality of life and incurs substantial healthcare costs.” 

CKD is estimated to affect one in ten people worldwide, equivalent to around 850 million people.2 It is the tenth leading cause of death and is projected to become the fifth most common cause of death by 2050.3 Diabetes, cardiovascular disease and obesity are independent risk factors for CKD and represent a major global health burden.4

Source: George Institute for Global Health

References

  1. Badve S et al. Effects of glucagon-like peptide-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2024. https://doi.org/10.1016/S2213-8587(24)00271-7
  2. Jager KJ, et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int. 2019. https://doi.org/10.1016/j.kint.2019.07.012 
  3. GBD 2021 Forecasting Collaborators. Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021. Lancet. 2024. https://doi.org/10.1016/S0140-6736(24)00685-8 
  4. The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration. Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardio-metabolic risk factors between 1980 and 2010: comparative risk assessment. Lancet Diabetes Endocrinol. 2015. https://doi.org/10.1016/S2213-8587(14)70102-0 
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Regular Checkups may Forestall Kidney Disease Progression

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Photo by Robina Weermeijer on Unsplash

A new Japanese ecological study revealed that participation rates for Specific Health Checkups (SHC participation rates) had significant negative effects on standardised incidence rates (SIRs) of treated end-stage kidney disease (ESKD) and prevalence of chronic kidney disease (CKD). The findings support the importance of increasing SHC participation rates at the population level and encouraging people to undergo regular health checkups.

These factors were all relative to each of Japan’s administrative regions, known as prefectures. The findings were reported in Clinical and Experimental Nephrology.

“Japan has one of the highest incidence and prevalence rates of treated ESKD and substantial regional variation in the incidence of treated ESKD despite a uniform health care and insurance system and low ethnic and racial diversity,” said Dr Wakasugi, the corresponding author of the study. “Large variations have been observed by prefecture in participation rates for SHC, an annual health screening program introduced by Japan’s Ministry of Health, Labour and Welfare since 2008 to identify individuals requiring specific health guidance to reduce the number of people having or at risk for, metabolic syndrome.”

Using five sources of nationwide open data, the study revealed that SHC participation rates had significant direct negative effects on prefecture-specific standardised incidence rates (SIRs) and the prefecture-specific prevalence of CKD. Furthermore, through SHC participation rates, the ratio of nephrology specialists had a significant indirect negative effect on prefecture-specific SIRs, suggesting that a higher prefecture-specific ratio of nephrology specialists was associated with lower prefecture-specific SIRs. The structural equation modelling model explained 14% of the variance in prefecture-specific SIRs, indicating that prefecture-specific SHC participation rates can partially explain regional variation in prefecture-specific SIRs of treated ESKD.

“Our findings concord with the Neyagawa Health Checkups and Health Care in Kokuho Database study, which showed that men who did not attend health checkups and did not undergo a kidney test using dipstick urinalysis and/or serum creatinine measurement at medical facilities were at significantly higher risk of treated ESKD than those who attended checkups, especially among those aged ≥ 75 years,” said Dr Wakasugi. “Our findings provide evidence to support the importance of increasing SHC participation rates from a population-level perspective and encouraging people to undergo health checkups.”

Source: EurekAlert