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.
Researchers at Children’s Hospital of Philadelphia (CHOP), along with several academic partners, announced the primary results of the Pediatric KIDney Stone (PKIDS) trial, the largest comparative effectiveness study of surgical interventions for children and adolescents with kidney stones. The CHOP-led PKIDS trial, with two published studies, marks a significant breakthrough by offering stronger evidence for treating stones of varying sizes, including new information on patient experiences after surgery, thus reducing uncertainty and empowering informed decision-making for patients, caregivers, and physicians.
Kidney stones were once largely a disease that affected adults. However, kidney stones in children have been on the rise in recent decades, doubling the likelihood that a child will develop a kidney stone. As a result, CHOP founded the PKIDS Care Improvement Network in 2019, which now includes 31 sites in the United States and Canada.
Ureteroscopy (an endoscopic outpatient procedure), shockwave lithotripsy (a noninvasive outpatient procedure) and percutaneous nephrolithotomy (a minimally invasive surgery with a short hospital stays) are the procedures used to treat children and adults with kidney stones. Most children and adolescents with kidney and ureteral stones are treated with ureteroscopy despite uncertainty of which procedure is more effective and their impact on patients’ lives. As pioneers in urology, CHOP leaders aimed to enhance pediatric patient and caregiver decision-making for kidney stone surgeries while enabling urologists to adopt techniques for optimal outcomes, including patient-selected experiences.
In the first study in JAMA Network Open, Tasian and his team enrolled 1142 patients aged 8 to 21 with kidney and/or ureteral stones between 2020 and 2023 at all 31 sites in the United States and Canada. Researchers evaluated ureteroscopy against shockwave lithotripsy and found that shockwave lithotripsy was associated with less pain and fewer urinary symptoms compared with those who had ureteroscopy. No meaningful differences were detected in stone-free rates for the procedures.
In the other CHOP-led study in JAMA Network Open, Jonathan S. Ellison, MD, an Associate Professor of Urology at the Medical College of Wisconsin and Pediatric Urologist at Children’s Wisconsin, and the PKIDS team compared percutaneous nephrolithotomy (PCNL) and ureteroscopy. That study found that for children with larger stones, PCNL not only cleared more stones effectively but also led to a better overall recovery experience than ureteroscopy.
Overall, the authors emphasised the post-surgery experiences of children, noting that quality of life factors, such as the loss of school time for children and work time for caregivers, are crucial in determining effective treatment options. While the authors are planning further research, they also hope these findings will lead to immediate improvements for families.
“The PKIDS trial demonstrated that ureteroscopy and shockwave lithotripsy remove stones equally well and that patients having shockwave lithotripsy recover more quickly after surgery with less pain and fewer urinary symptoms. Our findings provide new information that allow for tailored approaches to kidney stone treatment for children and their families,” said Gregory E. Tasian, MD, MSc, MSCE, Director of the PKIDS network and an attending pediatric urologist in the Division of Urology at Children’s Hospital of Philadelphia. “Although future clinical trials are important, we hope that clinical practice guidelines will consider outcomes that matter to patients.”
Urinary incontinence is a devastating condition, leading to significant adverse impacts on patients’ mental health and quality of life. Disorders of urination are also a key feature of all neurological disorders.
A USC research team has now made major progress in understanding how the human spinal cord triggers the bladder emptying process. The discovery could lead to exciting new therapies to help patients regain control of this essential function.
In the pioneering study, a team from USC Viterbi School of Engineering and Keck School of Medicine of USC has harnessed functional ultrasound imaging to observe real-time changes in blood flow dynamics in the human spinal cord during bladder filling and emptying.
The work was published in Nature Communications and was led by Charles Liu, the USC Neurorestoration Center director at Keck School of Medicine of USC and professor of biomedical engineering at USC Viterbi, and Vasileios Christopoulos, assistant professor at the Alfred E. Mann Department of Biomedical Engineering.
The spinal cord regulates many essential human functions, including autonomic processes like bladder, bowel, and sexual function. These processes can break down when the spinal cord is damaged or degenerated due to injury, disease, stroke, or aging. However, the spinal cord’s small size and intricate bony enclosure have made it notoriously challenging to study directly in humans.
Unlike in the brain, routine clinical care does not involve invasive electrodes and biopsies in the spinal cord due to the obvious risks of paralysis.
Furthermore, fMRI imaging, which comprises most of human functional neuroimaging, does not exist in practical reality for the spinal cord, especially in the thoracic and lumbar regions where much of the critical function localises.
“The spinal cord is a very undiscovered area,” Christopoulos said. “It’s very surprising to me because when I started doing neuroscience, everybody was talking about the brain. And Dr. Liu and I asked, “What about the spinal cord?”
“For many, it was just a cable that transfers information from the brain to the peripheral system. The truth was that we didn’t know how to go there—how to study the spinal cord in action, visualize its dynamics and truly grasp its role in physiological functions.”
Functional ultrasound imaging: A new window into the spinal cord
To overcome these barriers, the USC team employed functional ultrasound imaging (fUSI), an emerging neuroimaging technology that is minimally invasive. The fUSI process allowed the team to measure where changes in blood volume occur on the spinal cord during the cycle of urination.
However, fUSI requires a “window” through the bone to image the spinal cord. The researchers found a unique opportunity by working with a group of patients undergoing standard-of-care epidural spinal cord stimulation surgery for chronic low back pain.
“During the implantation of the spinal cord stimulator, the window we create in the bone through which we insert the leads gives us a perfect and safe opportunity to image the spinal cord using fUSI with no risk or discomfort to the study volunteers,” said co-first author Darrin Lee, associate director of the USC Neurorestoration Center, who performed the surgeries.
“While the surgical team was preparing the stimulator, we gently filled and emptied the bladder with saline to simulate a full urination cycle under anaesthesia while the research team gathered the fUSI data,” added Evgeniy Kreydin from the Rancho Los Amigos National Rehabilitation Center and the USC Institute of Urology, who was already working closely with Liu to study the brain of stroke patients during micturition using fMRI.
“This is the first study where we’ve shown that there are areas in the spinal cord where activity is correlated with the pressure inside the bladder,” Christopoulos said.
“Nobody had ever shown a network in the spinal cord correlated with bladder pressure. What this means is I can look at the activity of your spinal cord in these specific areas and tell you your stage of the bladder cycle – how full your bladder is and whether you’re about to urinate.”
Christopoulos said the experiments identified that some spinal cord regions showed positive correlation, meaning their activity increased as bladder pressure rose, while others showed negative (anti-correlation), with activity decreasing as pressure increased. This suggests the involvement of both excitatory and inhibitory spinal cord networks in bladder control.
“It was extremely exciting to take data straight from the fUSI scanner in the OR to the lab, where advanced data science techniques quickly revealed results that have never been seen before, even in animal models, let alone in humans,” said co-first author Kofi Agyeman, biomedical engineering postdoc.
New hope for patients
Liu has worked for two decades at the intersection of engineering and medicine to develop transformative strategies to restore function to the nervous system. Christopoulos has spent much of his research career developing neuromodulation techniques to help patients regain motor control.
Together, they noted that for patients, retaining control of the autonomic processes that many of us take for granted is more fundamental than even walking.
“If you ask these patients, the most important function they wanted to restore was not their motor or sensory function. It was things like sexual function and bowel and bladder control,” Christopoulos said, noting that urinary dysfunction often leads to poor mental health. “It’s a very dehumanising problem to deal with.”
Worse still, urinary incontinence leads to more frequent urinary tract infections (UTIs) because patients must often be fitted with a catheter. Due to limited sensory function, they may not be able to feel that they have an infection until it is more severe and has spread to the kidneys, resulting in hospitalisation.
This study offers a tangible path toward addressing this critical need for patients suffering from neurogenic lower urinary tract dysfunction. The ability to decode bladder pressure from spinal cord activity provides proof-of-concept for developing personalised spinal cord interfaces that could warn patients about their bladder state, helping them regain control.
Currently, almost all neuromodulation strategies for disorders of micturition are focused on the lower urinary tract, largely because the neural basis of this critical process remains unclear.
“One has to understand a process before one can rationally improve it,” Liu said.
This latest research marks a significant step forward, opening new avenues for precision medicine interventions that combine invasive and noninvasive neuromodulation with pharmacological therapeutics to make neurorestoration of the genitourinary system a clinical reality for millions worldwide.
New research presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) reveals the presence of microplastics in human reproductive fluids, raising important questions about their potential risks to fertility and reproductive health.[1]
The study abstract appears in Human Reproduction, one of the world’s leading reproductive medicine journals.
Researchers examined follicular fluid from 29 women and seminal fluid from 22 men, both of which play critical roles in natural conception and assisted reproduction.
A range of commonly used microplastic polymers, including polytetrafluoroethylene (PTFE), polystyrene (PS), polyethylene terephthalate (PET), polyamide (PA), polypropylene (PP) and polyurethane (PU), were identified in both groups.
Microplastics were present in 69% of the follicular fluid samples analysed. Notably, the most frequently detected polymer was PTFE, found in 31% of the samples. This was followed by PP (28%), PET (17%), PA (14%), polyethylene (PE) (10%), PU (10%) and PS (7%), in descending order of prevalence.
In male seminal fluid samples, microplastics were found in 55% of those analysed. PTFE again emerged as the most prevalent polymer, identified in 41% of the samples. Other polymers detected included PS (14%), PET (9%), PA (5%), and PU (5%), though in lower concentrations.
To prevent contamination, all samples were collected and stored in glass containers and underwent chemical treatment before analysis using laser direct infrared microscopy.
Lead researcher Dr. Emilio Gomez-Sanchez commented, “Previous studies had already shown that microplastics can be found in various human organs. As a result, we weren´t entirely surprised to find microplastics in fluids of the human reproductive system, but we were struck by how common they were – found in 69% of the women and 55% of the men we studied.”
Microplastics are defined as plastic particles under 5mm in size, and there is evidence that they pose a threat to environmental and public health.[2] While this research did not directly assess how microplastics affect fertility, their detection highlights the need to explore possible implications for human reproductive health.
“What we know from animal studies is that in the tissues where microplastics accumulate, they can induce inflammation, free radical formation, DNA damage, cellular senescence, and endocrine disruptions”, continued Dr Gomez-Sanchez. “It’s possible they could impair egg or sperm quality in humans, but we don’t yet have enoughevidence to confirm that.”
The research team plans to expand their analysis to a larger cohort, alongside detailed lifestyle and environmental exposure questionnaires. Further phases of the project will also explore the potential relationship between the presence of microplastics and oocyte and sperm quality.
Dr Gomez-Sanchez stressed that fertility is influenced by many factors, including age, health, and genetics, and that the findings should not cause alarm among those trying to conceive. “There’s no need for alarm at this point. Microplastics are just one of many elements that may play a role in fertility. However, it is sensible to consider ways of reducing our exposure to them. Simple steps, such as using glass containers to store and heat food, or limiting the amount of water we consume from plastic bottles, can help minimise our intake.”
[1] Gomez-Sanchez, E., et al. (2025) Unveiling the Hidden Danger: Detection and characterisation of microplastics in human follicular and seminal fluids. Human Reproduction. [insert link when available]
[2] Wang, L., Yin, Y., & He, X. (2024). The hidden threat: Unraveling the impact of microplastics on reproductive health. Science of the Total Environment, 912, 173177.
Arriving home after a long day may be a relief, but for some people, seeing their front door or inserting a key into the lock triggers a powerful urge to pee. Known as “latchkey incontinence,” this phenomenon is the subject of a new study by researchers at the University of Pittsburgh who found that mindfulness training and/or non-invasive brain stimulation could reduce bladder leaks and feelings of urgency evoked by these cues.
The findings of the pilot study, the first evaluation of brain-based therapies for urinary incontinence, are published in the latest issue of the journal Continence.
“Incontinence is a massive deal,” said senior author Dr. Becky Clarkson, research assistant professor in the Pitt School of Medicine Division of Geriatrics and co-director of the Continence Research Center. “Bladder leaks can be really traumatizing. People often feel like they can’t go out and socialise or exercise because they’re worried about having an accident. Especially for older adults, this feeds into social isolation, depression and functional decline. Our research aims to empower people with tools to get back their quality of life.”
Latchkey incontinence, or situational urgency urinary incontinence, is bladder leakage triggered by specific environments or scenarios. Common cues include one’s front or garage door, running water, getting into a car or walking past public restrooms.
According to lead author Dr. Cynthia Conklin, associate professor in the Pitt Department of Psychiatry, latchkey incontinence is a type of Pavlovian conditioning. Like Pavlov’s dogs, which salivated upon hearing a bell that they associated with food, years of going to the bathroom immediately upon entering the house can condition one to feel strong bladder urgency when seeing the front door.
In a previous study, Clarkson and Conklin showed participants pictures of their own front doors or other triggers versus “safe” images of things that did not evoke urgency while they had an MRI of their brain. A part of the brain called the dorsolateral prefrontal cortex was more active when participants viewed urgency-related images.
“The prefrontal cortex is the seat of cognitive control,” said Clarkson. “It’s the executive function center of the bladder, the bit that is telling you, ‘Okay, it’s time to go. You should find somewhere to go.’”
The researchers hypothesised that activating this part of the brain during exposure to urgency cues, through mindfulness and/or with transcranial direct current stimulation (tDCS) of the brain, could improve participants’ ability to regulate responses to these cues and control urgency and leakage.
They recruited 61 women aged over 40 who reported regular situationally triggered bladder leaks and randomly assigned them to one of three groups: Participants either listened to a 20-minute mindfulness exercise, received tDCS or both while viewing personal trigger photos.
The mindfulness exercise, developed by coauthor Dr Carol Greco, associate professor of psychiatry and physical therapy at Pitt, was like a typical body scan practice that instructs participants to move through their body, bringing attention to each part in turn. But unlike most body scans, it included specific acknowledgment of bladder sensation.
After completing four in-office sessions over five to six days, participants in all three groups experienced reduced urgency when they viewed trigger cues. Women in all three groups also reported an improvement in the number of urgency episodes and leaks after completing the sessions.
Although this pilot study did not have a control group, for comparison, the researchers say that the magnitude of improvement from tDCS and mindfulness was similar to what other research has reported for interventions such as medications and pelvic floor therapy.
“Although we need to do more research, these results are really encouraging because they suggest that a behavioral tool like mindfulness can be an alternative or additional way to improve symptoms,” said Conklin. “Balancing multiple prescriptions is a big issue among older adults, and a lot of people are reluctant to take another medication, so I think that’s one of the reasons that we saw such high acceptability of non-pharmacologic interventions in this study.”
More than 90% of recruited participants completed the study.
“Participants loved it,” said Clarkson. “Almost everyone who started the study finished it, even though coming into the office four days within one week was quite a big commitment. We got really great feedback, and a lot of women told us that they continue to use the mindfulness exercise in their daily lives.”
“For the first time in 20 years of doing research, we got thank you cards!” added Conklin. “I think that incontinence is such a taboo subject, and a lot of people find it difficult to talk about, so they often don’t even realize that there are treatments out there. But you don’t have to suffer in silence.”
Now, the researchers are planning to explore whether the mindfulness component of the study could be helpful in independent living facilities to reach a wide range of older adults. They also hope to eventually develop an app-based tool for smartphones.
A UCLA Health surgical team has performed the first-in-human bladder transplant.
The surgery was successfully completed at Ronald Reagan UCLA Medical Center on May 4, 2025. The team was led by Dr Nima Nassiri, a urologic transplant surgeon and director of the UCLA Vascularized Composite Bladder Allograft Transplant Program, with assistance from Dr Inderbir Gill, founding executive director of USC Urology.
“Bladder transplantation has been Dr Nassiri’s principal academic focus since we recruited him to the UCLA faculty several years ago,” said Dr Mark Litwin, UCLA Urology Chair, “It is incredibly gratifying to see him take this work from the laboratory to human patients at UCLA, which operates the busiest and most successful solid-organ transplant program in the western United States.”
“This first attempt at bladder transplantation has been over four years in the making,” Nassiri said. “For the appropriately selected patient, it is exciting to be able to offer a new potential option.”
The patient had lost most of his bladder during a tumour removal, leaving the remainder too small and compromised to work. Both of his kidneys were also subsequently removed due to renal cancer in the setting of pre-existing end-stage kidney disease. As a result, he was on dialysis for seven years.
The biggest risks of organ transplantation are the body’s potential rejection of the organ and side-effects caused by the mandatory immune suppressing drugs given to prevent organ rejection.
“Because of the need for long-term immunosuppression, the best current candidates are those who are already either on immunosuppression or have an imminent need for it,” Nassiri said.
Nassiri and Gill collaborated for several years to develop the surgical technique. Numerous pre-clinical procedures were performed at USC and OneLegacy, Southern California’s organ procurement organisation, to prepare for the first human bladder transplant.
During the complex procedure, the surgeons transplanted the donated kidney, following that with the bladder. The new kidney was then connected to the new bladder using the technique that Nassiri and Gill pioneered. The entire procedure lasted approximately eight hours.
“The kidney immediately made a large volume of urine, and the patient’s kidney function improved immediately,” Nassiri said. “There was no need for any dialysis after surgery, and the urine drained properly into the new bladder.”
Current treatment for severe terminal cases of bladder dysfunction or a bladder that has been removed due to various conditions includes replacement or augmentation of the urinary reservoir. These surgeries use a portion of a patient’s intestine to create a new bladder or a pathway for the urine to exit the body.
While these surgeries can be effective, they come with many short-and long-term risks that compromise a patient’s health such as internal bleeding, bacterial infection and digestive issues.
“A bladder transplant, on the other hand, results in a more normal urinary reservoir, and may circumvent some short- and long-term issues associated with using the intestine,” Nassiri said.
As a first-in-human attempt, there are naturally many unknowns associated with the procedure, such as how well the transplanted bladder will function immediately and over time, and how much immunosuppression will ultimately be needed.
Bladder transplants have not been done previously, in part because of the complicated vascular structure of the pelvic area and the technical complexity of the procedure. As part of the research and development stage, Nassiri and Gill successfully completed numerous practice transplantation surgeries at Keck Medical Center of USC, including the first-ever robotic bladder retrievals and successful robotic transplantations in five recently deceased donors with cardiac function maintained on ventilator support.
The two surgeons also undertook several non-robotic trial runs of bladder recovery at OneLegacy, allowing them to perfect the technique while working closely with multi-disciplinary surgical teams.
The bladder is strictly within the domain of urologists. At UCLA, kidney transplantation is also housed within the department of urology. This is why the combined kidney and bladder transplant was ultimately performed at UCLA, which has the necessary infrastructure, clinical expertise, and multidisciplinary support to carry out the procedure and manage the patient from pre-transplant evaluation through post-transplant care, all within the one department.
The procedure was performed as part of a UCLA clinical trial. Nassiri hopes to perform more bladder transplants in the near future.
UCLA Urology has long been at the frontier of urologic transplantation, with pioneering research in kidney transplantation and now, bladder transplantation.
A court case over the trade names of two urinary tract infection (UTI) drugs has been settled. The court ordered that Cipla Medpro be restrained from using the trade name Furizome as it is too similar to Adcock Ingram’s UTI drug Urizone, leading to potential confusion by consumers. In his ruling, Justice James Lekhuleni of the High Court, Western Cape Division, who stated that despite safeguards against confusion in prescribing, ultimately “doctors are human”, so miscommunications could occur – and that the agency of patients cannot be ignored.
The trademark infringement case was brought by three applicants: Adcock Ingram Limited, Adcock Ingram Healthcare (Pty) LTD, and Italian company Zambon S.P.A. Zambon is the owner of the name Urizone, which is used under licence. Urizone had been launched in South Africa in 1993. The applicants stated that more than 3 million sachets had been sold between 2011 and 2023, with R5 million in advertising spent to promote the drug between 2018 and 2022 alone.
The applicants brought the case that Cipla Medpro’s Furizome, with the active ingredient fosfomycin, was too similar to their own product, Urizone, which contained the same ingredient in 3g sachets, and thus could confuse consumers. They alleged that Cipla Medpro sought to capitalise on the reputation earned by Urizone.
The applicants made the case that, despite Urizone being made available as a generic, none of the pharmaceutical companies producing it chose to use the name. When Furizome was launched, Adcock Ingram sent a letter of demand to Cipla to stop using the name due to its . Cipla, through its attorneys, rebutted the claim, saying that the two are sufficiently distinct to avoid confusion, with the “F” alluding to the fosfomycin ingredient. Cipla contended that it had already submitted the name through SAHPRA, and
Cipla also contended that the consumer – the patient – would not be misled during the prescribing and purchase of a schedule 4 medication as they would be informed by the pharmacist of the two different drugs.
In considering the judgment, the court noted that a test as to whether trademarks are be similar can be mode on a phonetic basis, or if they conceptually or visually similar. A trademark’s essential function is to indicate the origin of the goods in connection with which it is used. The “N” and “M” where seen as visually and phonetically similar, and “furi” was similar phonetically to “uri“. This could cause confusion and miscommunication even between doctors as to what drug they had prescribed a patient.
While Justice Lekhuleni acknowledged the safeguards of prescribing schedule 4 medications, he pointed out that the general public had become much more knowledgeable about prescription drugs in the past two decades. On this, he wrote “…the reality is that patients are involved in the process of deciding which medicines they will use, and that creates the risk of confusion. This situation in turn creates a responsibility upon pharmaceutical companies to make sure that they adopt trade marks that are not confusingly similar.”
A University of Iowa-led research team has found that urinary incontinence may be associated with a greater risk for cardiovascular disease in women.
Urinary incontinence is a common condition, especially in older adults. Previous studies have stated that it can affect between 38% and 60% of women. The researchers aimed to find out whether urinary incontinence was linked to a decline in physical activity, which can lead to a host of health issues, including greater risk for cardiovascular disease.
In the study, the researchers – led by Lisa VanWiel, assistant professor at the University of Wisconsin-La Crosse who in April earned her doctorate in health and human physiology from Iowa – analysed medical records over two years from more than 20 000 female patients in the Hartford Healthcare system in Connecticut. Of those patients, 5.4% reported through a questionnaire to have urinary incontinence. All patients were asked to rate their level of physical activity in the questionnaire.
The researchers found that the respondents with urinary incontinence did not report engaging in less physical activity than those who did not have the condition. But the team did find an association between patients with urinary incontinence and cardiovascular disease risk factors or events, such as dyslipidemia, type 2 diabetes, and stroke.
“There is an association between incontinence and cardiovascular disease (CVD) risk,” the study authors write. “Women should be screened for incontinence regularly as it may contribute to CVD risk, and women with CVD risk factors should be screened for undiagnosed incontinence.”
New insights into what causes the painful and disruptive symptoms of urinary tract infections (UTIs) could offer hope for improved treatment. Nearly one in three women will experience UTIs before the age of 24, and many elderly people and those with bladder issues from spinal cord injuries can experience multiple UTI’s in a single year.
Findings from a new study led by Flinders University’s Dr Luke Grundy and SAHMRI’s Dr Steven Taylor show that UTIs cause the nerves in the bladder to become hypersensitive resulting in the extremely painful and frequent urge to urinate, pelvic pain, and burning pain while urinating.
“We found that UTIs, caused by bacterial infections such as E. coli, can significantly alter the function and sensitivity of the nerves that usually detect bladder fulness, a phenomenon known as ‘bladder afferent hypersensitivity’, says Dr Grundy, from the College of Medicine and Public Health.
“The study was the first of its kind to explore the impact of UTIs on the sensory signals that travel from the bladder to the brain, and the direct link this response has to causing bladder pain and dysfunction.”
A normal bladder will expand to store urine and can store up to two cups of urine for several hours. Once full, the bladders nervous system will signal that it is time to urinate, or empty the bladder.
Described in Brain, Behavior, & Immunity – Health, researchers analysed how UTIs cause sensory nerves that respond to bladder distension to become hypersensitive, so that they send signals of bladder fulness, even when the bladder is not yet full.
“Our findings show that UTIs cause the nerves in the bladder to become overly sensitive, which means that even when the bladder is only partly filled, it can trigger painful bladder sensations that would signal for the need to urinate,” he says.
“We think that these heightened sensory responses may serve as a protective mechanism, alerting the body to the infection and prompting more frequent urination to expel the bacteria.”
Building on previous research, the new study reveals a deeper understanding of how UTIs affect bladder function and the nervous system, and raises important questions about the role of bladder hypersensitivity in the development of UTI-related symptoms.
“Our findings go further in identifying the significant changes that occur during UTIs and provide a clearer picture of the mechanisms behind the painful and disruptive bladder sensations often associated with these infections,” says Dr Grundy.
The study also suggests that better understanding and targeting of bladder afferent hypersensitivity could improve treatment options for patients suffering from recurrent UTIs or other bladder conditions where sensory dysfunction plays a role.
“Theoretically we should be able to find a way to address hypersensitive nerves in the bladder and reduce or eliminate the painful and debilitating symptoms of a UTI,” he adds. This would improve quality of life whilst antibiotics are taking care of the infection.
Researchers are striving to address the limited treatments available for bladder pain by exploring how the findings may translate into clinical practice and improve the management of UTIs in patients.
Researchers have identified a subset of brain cells in mice that act as the master regulators of urination.
The research, published as a Reviewed Preprint in eLife, is described by editors as an important study with convincing data showing that oestrogen receptor 1-expressing neurons (ESR1+) in the Barrington’s nucleus of the mouse brain coordinate both bladder contraction and relaxation of the external urethral sphincter.
Urination requires the coordinated function of two units of the lower urinary tract. The detrusor muscle of the bladder wall relaxes to allow the bladder to fill and empty, while the external sphincter opens when it’s appropriate to allow urine to flow out, but otherwise keeps tightly shut.
“Impairment of coordination between the bladder muscle and the sphincter leads to various urinary tract dysfunctions and can significantly degrade a person’s quality of life,” says first author Xing Li, Advanced Institute for Brain and Intelligence, School of Physical Science and Technology, Guangxi University, Nanning, China. “But although we know the individual nerve signalling pathways that control each of these urinary tract components, we don’t know which brain areas ensure they cooperate at the right time.”
To explore this, the authors used state-of-the-art live cell imaging to study the activity of brain cells in anaesthetised and awake mice during urination. They focused on a brain region called the pontine micturition centre (PMC), otherwise known as the Barrington’s nucleus, and compared the activity of different PMC nerve cell subtypes.
In their first experiments, they measured the activity of the cells as the bladder empties by measuring changes in levels of calcium. This revealed that the electrical firing rate of a subset of PMC cells expressing estrogen receptors (PMCESR1+ cells) was tightly linked to bladder emptying. When they combined this with monitoring bladder physiology, they found that it was not only the timing of PMCESR1+ cell activity that correlated with bladder emptying, but the strength of cell electrical activity, too.
Next, they tested what happened to urination if they blocked or triggered the PMCESR1+ cells. They found that when PMCESR1+ cell activity was blocked, the amount of urine the mice passed was significantly reduced and ongoing urination was suspended from the moment the cells were inactive. To understand the mechanism behind this, they measured the activity of the bladder muscle and sphincter. They discovered that both increase of bladder pressure and sphincter muscle bursting activity associated with bladder emptying both stopped when PMCESR1+ cell activity was blocked during an ongoing voiding even. Similarly, when PMCESR1+ cells were artificially activated using light, bladder emptying occurred 100% of the time. This suggests that PMCESR1+ cells work as a reliable master switch that either initiates or suspends bladder emptying.
To test whether PMCESR1+ cells can influence bladder emptying independently of controlling the sphincter, they disconnected either the nerve carrying messages from the brain to the sphincter, or the nerve carrying messages from the brain to the bladder. They found that PMCESR1+ cell control of the bladder was fully operational even when communication to the sphincter was blocked, and vice versa. This showed the cells could control the bladder and sphincter independently of one another, but the question remained: could they coordinate the action of the bladder muscle and sphincter together? That is, operate them in a controlled, perfectly timed manner, to trigger bladder emptying when appropriate?
To explore this, they simultaneously recorded bladder pressure and electromyography measurements of sphincter activity. The timing of bladder pressure changes immediately before sphincter bursting activity was consistent for both spontaneous bladder emptying and emptying caused by activating the PMCESR1+ cells, showing that these cells can coordinate the two steps in a precisely temporal sequence and controlled way.
“Our study shows that a subset of cells in the Barrington’s nucleus of the brain can initiate and suspend bladder emptying with 100% accuracy when needed, for example, to release only a small volume for landmarking by animals, or for a human to urinate into a small sample tube for a health check,” concludes senior author Xiaowei Chen, Third Military Medical University, and Chongqing Institute for Brain and Intelligence, China. “While other cells will no doubt be involved in perfect urination control, our pinpointing of PMCESR1+ cells’ crucial role in bladder–sphincter coordination will aid the development of targeted therapies for treating urination dysfunction caused by brain or spinal cord injury or peripheral nerve damage.”
