Older people, particularly women, who start treatment with thiazide-type diuretics are at increased risk of developing low sodium levels in the blood. This is shown by a large registry study from the Karolinska Institutet published in JAMA Network Open.
Thiazides are a common group of medicines used to treat high blood pressure. In some cases, however, treatment can lead to hyponatraemia. Low sodium levels can cause symptoms such as fatigue, nausea, confusion and, in severe cases, seizures.
In the study, the researchers compared the risk of hyponatraemia in people who started treatment with thiazides with the risk in people who were instead given calcium channel blockers, another type of blood pressure medication. The study included a total of 159 080 adults in the Stockholm area and is based on data from the so-called Stockholm Sodium Cohort.
The researchers from KI SÖS, Department of Laboratory Medicine and Department of Molecular Medicine and Surgery at KI, followed the participants for the first two years after the start of treatment. The risk was particularly high among older women. Among women aged 80 or over, 2.4% developed severe hyponatraemia. For this group, this meant that one in 53 people treated was affected. In women under 65, however, the risk was low.
“Our findings show that the link between thiazides and low blood sodium levels is very weak in younger people, but clear in older people, particularly in women,” says Cecilia Bergh Fahlén, a PhD student at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.
The researchers believe that the findings may inform clinical decisions regarding the treatment of high blood pressure.
“For vulnerable patients, such as older women, there may be good reasons for considering alternative blood pressure medications. If thiazides are used nonetheless, it is important to monitor sodium levels in the blood”, says Cecilia Bergh Fahlén.
Every minute your kidneys are hard at work, filtering around 200 litres of blood, removing waste, balancing salts and fluids, and regulating blood pressure. This happens without any conscious effort on your part.
But when your kidneys begin to fail, the consequences are devastating, including fatigue, fluid buildup and heart complications. Some people eventually need dialysis or a transplant to stay alive.
Kidney disease is one of the fastest-growing causes of death across the world. Around 850 million people are living with some form of it, more than the combined number of people affected by diabetes and cancer. Chronic kidney disease – when your kidneys slowly lose the ability to do their job – causes approximately 1.5 million deaths each year globally and that toll is rising.
But kidney disease develops silently, with few symptoms until it is already severe.
And the burden is not shared equally. People of African ancestry are four times more likely to develop the most severe form of kidney failure than people of European ancestry. In sub-Saharan Africa, rates of high blood pressure and type 2 diabetes are rising too. Both are leading drivers of kidney damage. Around 30% of adults in sub-Saharan Africa have high blood pressure, and 25 million (one in 20 adults) have diabetes) – mostly undiagnosed and untreated.
Sub-Saharan Africa has lower numbers of kidney specialists, dialysis facilities and transplant services per capita than the rest of the world. Africa as a whole has fewer than one nephrologist per million people. In some African countries there are no kidney specialists at all. The global median is around 10 per million. In high-income countries the figure reaches 23 per million. For most Africans who reach kidney failure, there is simply no treatment available.
Identifying who is at risk before their kidneys fail is therefore vital.
Our recently published research fills a big gap here. We are members of the KidneyGenAfrica consortium, a pan-African partnership that aims to deliver research and training excellence in genomics of kidney disease.
We found new genetic variants that point to kidney disease risk in African populations. And we uncovered differences between the genetic risks faced by people living in Africa, on one hand, and people of African descent living in the North America and Europe, on the other.
This shows how important it is for medicine to be based on relevant research.
Understanding kidney disease
Kidney disease does not appear suddenly. It often develops gradually, shaped by a combination of factors. Some people carry genetic variants, small differences in their DNA, that make their kidneys more susceptible to damage.
Others face environmental risks such as high-salt diets, uncontrolled high blood pressure or diabetes infections. The use of herbal medicines, contaminated water and environmental toxins are risks too.
In most cases, it is the combinations of these factors that determine who gets sick and how quickly. But until recently, African populations had barely featured in the scientific conversation about this. Africa, home to the most genetically diverse human populations on Earth, have been represented in only a small fraction of the world’s genomic research.
That is beginning to change.
Large genetic study of Africans
We analysed genomic data from about 26,000 individuals across eastern, western and southern Africa, and around 81,000 individuals of African ancestry living elsewhere. It’s the largest genetic study of kidney function in continental Africans ever conducted.
Our study sheds new light on the genetics of chronic kidney disease across diverse African populations. It will also support future work aimed at improving prevention, diagnosis and treatment of kidney disease among these populations and worldwide.
The team used a method called a genome-wide association study, which scans the entire human genetic code to find variants linked to a particular trait or disease. Here, the trait of interest was estimated glomerular filtration rate, a standard blood test result that measures how efficiently the kidneys are filtering waste. A lower score signals poorer kidney function and higher risk of disease.
Analysing continental African populations alone, the study identified four relevant locations on genes, including two that hadn’t been reported before.
Adding African-ancestry populations across the diaspora, the number rose to 19 locations, three of them new. Four of these genetic locations were pinpointed with high precision. This means the team was able to identify the specific genetic variant most likely driving the effect, rather than simply flagging a region of the genome where something relevant was happening.
Each newly discovered location is now a potential target for future drugs or diagnostic tools.
The study also examined polygenic scores, which are tools that estimate a person’s overall risk of developing a disease. A key finding here was that scores built using data from genetically similar African populations performed better than scores derived from larger but genetically distant datasets.
This matters enormously for medicine in Africa: the science only works if the reference data matches the population it is meant to serve.
A gene that behaves differently on either side of the Atlantic
An important finding from the study concerns a gene called APOL1. Two variants of the APOL1 gene, known as G1 and G2, increase the risk of several serious forms of kidney disease in African Americans. It was widely assumed that the same risk would apply equally to people living on the African continent.
However, the data suggests otherwise. In continental Africa, these high-risk APOL1 variants occur at lower frequencies (and vary across regions of Africa). Their association with reduced kidney function is markedly weaker than in the African diaspora.
The same gene appears to behave differently depending on where a person lives and what population they descend from.
The finding matters for drug development. Clinical trials for kidney disease treatments must include people living in Africa and not just people of African descent living elsewhere.
What must happen now
Several things must follow from this research if it is to benefit people’s health:
African health systems must invest in early kidney disease detection. Simple, affordable blood and urine tests can identify kidney damage when lifestyle changes and medication can still make a difference. Genetic risk tools can help identify who needs screening most urgently.
Pharmaceutical companies must include continental African populations in their clinical trials.
The global research community must continue investing in African genomic infrastructure – research cohorts and large groups of consenting participants whose genetic and health data are collected and stored for analysis.
This research is evidence that African scientists, working with African communities, can generate knowledge that shifts the global picture. The world’s understanding of one of its most urgent health challenges will be sharper for it.
A combination of immunotherapy and targeted cancer treatment given before and after surgery may reduce the risk of recurrence and improve survival in patients with muscle‑invasive bladder cancer who cannot tolerate conventional chemotherapy. The findings come from a new study from Karolinska Institutet, published in The New England Journal of Medicine.
Muscle‑invasive bladder cancer is a serious disease with a high risk of recurrence. To lower the risk of recurrence, patients are often given cisplatin‑based chemotherapy before surgery, but around half of patients cannot receive this treatment, commonly due to impaired kidney function. In the phase 3 study, all participants underwent standard surgery, in which the bladder is removed. One of the groups also received a new combination treatment with the immunotherapy pembrolizumab and the targeted drug enfortumab vedotin before and after surgery.
Large differences between the groups
The results show that 75% of participants treated with the combination therapy were alive without recurrence two years after enrolment, compared with 39% in the control group. When the researchers looked at overall survival, a larger proportion of patients in the treatment group were also alive after two years. In addition, no tumour cells were found in the removed bladder tissue in 57% of patients in the treatment group, compared with 9% in the control group. In total, 344 participants from 27 countries took part in the study.
“These are very promising results for patients with few treatment options available before surgery. It is also reassuring that the treatment does not appear to affect the ability to proceed with surgery, which can otherwise be a concern when treatment is given beforehand,” says Anders Ullén, professor of oncology at the Department of Oncology‑Pathology at Karolinska Institutet and the study’s last author.
Side effects occurred in both groups
All patients who received the combination treatment experienced some form of side effect. Common side effects included itching and hair loss, and the most frequent serious side effect in both groups was urinary tract infection. Serious complications also occurred among those who underwent surgery alone, which the researchers note reflects the fact that many patients in this group are older and have other underlying health conditions.
“It is always important to balance the benefits of treatment against the risk of side effects. At the same time, the results indicate that the treatment may offer clinically meaningful improvements, reduce the risk of recurrence and improve survival for many patients. We hope that the findings can help inform future treatment practice,” says Anders Ullén.
One in ten emergency patients with visible blood in their urine die within three months of presenting at A&E, new research has found. The WASHOUT study, presented Monday 16 March at the European Association of Urology Congress (EAU26) in London, found that a scan within 48 hours could reduce this risk.
Such a scan also ensured patients with cancer were diagnosed significantly faster. Around 1 in 4 people who presented at A&E with visible blood in their urine had an underlying cancer, with the most common being bladder cancer, the study found.
Around 25 000 people visit UK A&E departments each year because they have blood in their urine. Currently, patients receive different care depending on which hospital they visit or even which doctor they see. This is because there are no guidelines built on real-world evidence for doctors to follow. Based on global figures, only around half (53%) of patients receive a scan and a third (35%) receive surgery, with others discharged home or admitted to the ward to watch how their symptoms progress, says the WASHOUT study.
The WASHOUT study drew on global data to show that rapid action is critical for better patient outcomes. A CT scan or cystoscopy to look inside the bladder within 48 hours of arriving at A&E should determine the most appropriate next steps – such as whether the person should be treated for bladder cancer. Patients who didn’t receive investigative tests or appropriate treatment were 2.5% more likely to die within the next three months compared to those who did. They also spent more time in hospital and were more likely to be readmitted with the same problem within three months.
For patients with an underlying cancer, those who received investigative tests within the first 48 hours of admission were diagnosed within one day on average. In contrast, patients who were discharged without investigation faced a significantly longer wait, with diagnosis taking on average three weeks.
The research team is now taking steps to incorporate their findings into clinical guidelines, to help hospital staff provide the best treatment for these patients.
The study looked at data from more than 8500 people across 380 hospitals around the world and followed their journey for 90 days after arriving at A&E with blood in their urine. It also considered other factors that might have affected results, including age, frailty and other underlying conditions.
Nikita Bhatt, consultant urologist at St Vincent’s University Hospital, Dublin, led the research being presented at EAU26. She said: “This is the largest study exploring how we should treat people who present at A&E with blood in their urine. It’s a common problem affecting thousands of people around the world, and these patients are usually very unwell. But too often they fall through the gaps because it isn’t obviously tied to a specific disease. Our findings show how important it is that doctors take the necessary steps to identify the cause of the problem. For patients, the message is clear: if you have visible blood in your urine, don’t ignore it. See your doctor as soon as you can. If it doesn’t clear up, keep pushing until you find an answer. I hope our study gives patients the encouragement to do that.”
Jacqueline Emeks, a patient advocate on the WASHOUT study, who was diagnosed with a kidney infection and sepsis after arriving at A&E with visible blood in their urine, agrees: “These findings highlight that blood in the urine should trigger immediate action. It’s not something to watch and wait. For patients, this should mean quicker triage, earlier investigations and faster treatment, translating into safer care, fewer delays, and a better chance of avoiding severe illness or long-term harm. Patients know their bodies and deserve to be taken seriously. Blood in urine is a red flag until proven otherwise.”
Prof Dr Joost Boormans, a member of the EAU Scientific Congress Office and a urologist at the Erasmus University Medical Center, Rotterdam, said: “This is an important study highlighting the scale of the problem that emergency blood in the urine presents, both for patients and our already over-stretched healthcare systems. It’s difficult to draw strong conclusions about specific conditions because blood in the urine can be caused by many things, including cancer, and this group of patients is very diverse. But this study shows that timely investigative tests can accelerate diagnosis and reduce patients’ risk of readmission and long hospital stays, both being significantly high as shown in the WASHOUT study. As urologists in emergency care, we should be aware of these numbers and do more to get an immediate diagnosis for people with blood in urine, to reduce the burden on our healthcare systems and give our patients the best outcomes.”
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
Prostate cancer screening compares favourably to screening for breast cancer in identifying significant cancers, reducing mortality and avoiding unnecessary harms, according to new research. The findings are presented on Sunday 15 March 2026 at the European Association of Urology Congress (EAU26) in London. The research is also accepted for publication in European Urology.
The researchers maintain that the similarities between the two forms of screening mean it is no longer rational to reject prostate cancer screening on one hand while endorsing screening for breast cancer on the other. Nevertheless, they recommend some caution given their research compares a trial with a population-based screening programme and across two different cancers.
Although breast and prostate cancer are the most commonly diagnosed cancers in Europe amongst men and women respectively, screening for the diseases is vastly different. Organised breast cancer screening programmes have been established across Europe for more than three decades. Prostate cancer screening has lagged behind, primarily due to concerns around the effectiveness of the PSA blood test and the risks of overdiagnosis and overtreatment. Nevertheless, many men undergo variable, ‘opportunistic’ screening for the disease, mostly based on self-referral.
Several prostate cancer screening trials in Europe have now reported long-term outcomes, showing a reduced risk of death from prostate cancer [1]. This risk reduction is similar to that seen in breast screening programmes.
The new analysis compares the two types of cancer screening in terms of the effectiveness of the diagnostic tests and levels of overdiagnosis. The researchers, from the German Cancer Research Centre in Heidelberg, Germany, drew on data from the PROBASE prostate cancer screening trial in Germany and the country’s breast cancer screening programme.
They used data from 39,392 men who underwent an initial PSA blood test as part of the PROBASE trial at age 45 or 50. They compared this with data from just over 2.8 million women, aged 50–69, who had a mammography as part of Germany’s organised breast cancer screening programme. They found:
PSA blood testing followed by an MRI scan leads to a higher number of false positives than mammography (37-42% vs 10%).
A similar proportion of men and women were referred for biopsy (0.8-2.4% for men and 1.1% for women) as men in the PROBASE trial were triaged before referral using various factors to determine the likelihood of significant cancer (known as risk stratification)
Biopsies were far more likely to identify significant cancer in prostate screening than in breast screening (50-68% vs 10%), indicating that fewer men were referred for biopsy unnecessarily.
The percentages of invasive cancers identified were similar across both prostate and breast cancer screening (60-74% vs 73%).
Prostate cancer screening was more likely to identify non-aggressive cancers than breast cancer screening (26-31% vs. 22%). However, in prostate cancer the option of active surveillance is well-established, and the researchers maintain this would limit the risk of overtreatment. Active surveillance involves monitoring lower grade cancers and only starting treatment (radiotherapy or surgery) if they progress.
Dr Sigrid Carlsson, who leads Clinical Epidemiology of Early Cancer Detection at the German Cancer Research Centre (DKFZ) in Heidelberg, is lead author of the research. She said: “Until we have a population-based screening programme for prostate cancer, we can’t make an exact like-for-like comparison with breast cancer. But we can make some informed assumptions based on the data from our trial, which shows that if prostate cancer screening were extended to the wider population, then the outcomes are likely to be very similar to breast cancer. Although our study used German data, the findings are applicable to other countries. The final question we now need to answer is: what will this cost compared to what we are already paying for opportunistic screening? And that work is already underway.”
Tobias Nordström is a clinical urologist and Associate Professor at the Karolinska Institute, Sweden and a member of the EAU Scientific Congress Office. He said: “There is much that prostate cancer screening can learn from breast cancer screening and that is why this analysis is an important addition to our knowledge base. As these kinds of comparisons are very challenging, the results do need to be taken with a level of caution. That said, the clear overall similarities between the outcomes for breast and prostate cancer screening show that we are moving in the right direction, ensuring prostate cancer screening offers more benefits than harm.”
Urology departments in England and Wales have reported seeing an increase in the number of 16- to 24-year-olds being admitted for bladder inflammation associated with ketamine use.
This appears to coincide with an increase in ketamine use – with the number of adults and teens entering treatment for ketamine abuse last year jumping substantially compared to even just a few years previously.
Ketamine abuse can have many affects on the bladder, causing frequent urination, night-time urination, sudden urges, leakage, inflammation, pain in the bladder or lower back and blood in the urine. These symptoms can be severe, make daily life very difficult and may even be permanent in some cases.
But a growing number of people are now using ketamine recreationally. It acts as a dissociative drug, causing users to feel detached from themselves and their surroundings. It can produce hallucinogenic, stimulant and pain-relieving effects, which last one to two hours.
Users typically snort or smoke powdered ketamine, or inject liquid ketamine or mix it into drinks in order to experience the drug’s effects. Snorting usually produces stronger effects and more noticeable symptoms than swallowing it.
Ketamine users can develop tolerance to the drug quickly, needing higher doses to get the same effects. This is probably due to the body and brain adapting to become more efficient at breaking down the drug. Frequent users often need to take twice the amount of occasional users to get the same effect.
The first recorded cases of ketamine affecting the bladder were reported in Canada in 2007, where nine people who used ketamine recreationally had severe bladder problems and blood in their urine. Later, a bigger study in Hong Kong found the same issues in 59 people who had used ketamine for more than three months.
Ketamine, as with any other drug, is metabolised in the body where it’s broken down and excreted in urine.
When ketamine is broken down, it turns into chemicals that can seriously harm the bladder. When these by-products stay in contact with the urinary tract for a long time, they irritate and damage the tissue.
The bladder is damaged first, because it holds urine the longest. Later, the ureters (tubes connecting the kidney to the bladder) and the kidneys can also be affected.
Over time, the bladder can shrink and become stiff, causing strong urinary symptoms. The ureters can become narrow and bent, sometimes described as looking like a “walking stick.” This can lead to backed-up urine in the kidneys (hydronephrosis).
Ketamine also increases oxidative stress, which damages cells and causes bladder cells to die. This breaks the protective bladder lining, making it leaky and overly sensitive.
All these changes can make the bladder overactive, extremely sensitive and painful, often causing severe urges to urinate and incontinence.
In the first stage, the bladder becomes inflamed. This can often be reversed by stopping ketamine and taking certain medication – such as anti-inflammatory drugs, pain relievers or prescription drugs that reduce bladder urgency and help the bladder lining heal.
In the second stage, the bladder can shrink or become stiff. In this stage, treatment is similar to stage one, but a bladder wash may also be required. This is where a catheter is used to put liquid medication directly into the bladder. The drug coats the bladder’s inner lining, helping to restore its protective layer and reduce inflammation.
Botulinum toxin injections may also be used to relax the bladder and reduce pain and urgency. Stopping ketamine remains essential to prevent further damage.
In the final stage, permanent damage occurs to the bladder and kidneys. Over time, if the kidneys are affected, it can lead to kidney failure. Dialysis (a treatment where waste products and excess fluid are filtered from the blood) or even surgery may be required to repair kidney function and the urinary system.
Although ketamine has been a class B drug since 2014, it’s unfortunately affordable and accessible – costing as little as £3 per gram in some parts of the UK. Raising awareness about the risks of ketamine use is essential to prevent these serious health problems.
Researchers at the Icahn School of Medicine at Mount Sinai, in collaboration with other leading institutions across the country, have published an innovative study that provides radiation oncologists with practical guidance to identify and protect female sexual organs during pelvic cancer treatment.
Published in the latest issue of Practical Radiation Oncology, this study addresses a long-standing gap in cancer care by bringing key female sexual anatomy into consideration during routine radiotherapy planning and survivorship research.
The study, “Getting c-literate: Bulboclitoris functional anatomy and its implications for radiotherapy,” synthesises current scientific knowledge and pairs it with original anatomic dissection, histology, and advanced imaging analysis. The work focuses on the bulboclitoris, a female erectile organ (consisting of the clitoris and the vestibular bulbs) that plays a central role in sexual arousal and orgasm and can be exposed to radiation during treatment for pelvic cancers.
“Pelvic radiotherapy can be life-saving, but it can also affect sexual function and quality of life,” said Deborah Marshall, MD, MAS, Assistant Professor, Departments of Radiation Oncology and Population Health Science and Policy at the Icahn School of Medicine at Mount Sinai; Division Chief of Women’s Health, Department of Population Health Science and Policy; and senior author of the study. “Compared to male sexual anatomy, female erectile structures have been largely invisible in standard radiation workflows. Our goal was to provide clinicians with a practical anatomy-grounded way to change that.”
Using detailed anatomic and radiologic correlation, the research team demonstrates how the bulboclitoris and related neurovascular structures can be identified on standard CT and MRI scans and consistently outlined (or “contoured”) for radiotherapy planning. This step-by-step guidance makes it feasible for clinicians to measure radiation dose to these tissues and begin linking exposure to patient-reported outcomes related to arousal and orgasm.
“This work builds upon our previous knowledge that the clitoris is not just an external structure,” Dr. Marshall said. “It includes an entire internal organ comprised of erectile tissues located just outside the pelvis, and those tissues matter for sexual health and, in particular, for female sexual pleasure. Once clinicians can reliably see and measure them, we can begin to ask better questions, have better conversations with patients, and ultimately deliver better care.”
Sexual function outcomes after pelvic radiotherapy have historically been understudied in women, limiting counselling, toxicity prevention strategies, and equitable survivorship care. By establishing a shared, standardised approach to identifying the bulboclitoris, the study lays the groundwork for future research to develop dose-volume constraints and mitigation strategies, as other organs at risk are managed in radiation oncology.
For clinicians, the framework enables routine contouring and dose reporting using CT alone when necessary, with MRI improving soft-tissue visualization when available. In the absence of prospective dose-response data, the authors recommend minimising radiation dose to the bulboclitoris when oncologically appropriate, using an “as low as reasonably achievable” approach.
For patients, the work supports more informed conversations about potential sexual side effects of pelvic radiotherapy, including changes in arousal, sensation, orgasm, lubrication, or pain. This research also promotes more personalized treatment planning that considers female sexual health and pleasure as a legitimate and important component of cancer survivorship.
Next steps include prospective research through Mount Sinai’s STAR program, deeper mapping of neurovascular anatomy relevant to sexual function, expanded educational resources for oncology and radiology teams, and improved patient-reported outcome measures that reflect diverse sexual practices and experiences.
Subtle abnormalities in kidney function – even within the range considered normal – may help identify people at risk of developing chronic kidney disease. This is shown in a new study from Karolinska Institutet, published in Kidney International. The researchers have therefore developed a web-based tool that could aid in early detection and thus primary prevention.
Chronic kidney disease is a growing global health concern afflicting 10−15% of adults worldwide, and is projected to become one of the top five leading causes of years of life lost by 2040. In the absence of effective screening programmes, patients are often diagnosed late, when more than half of their kidney function has already been lost.
To address this gap, researchers at Karolinska Institutet have constructed population-based distributions for estimated glomerular filtration rate (eGFR), the most widely used measure of kidney function. The aim is to help doctors identify people at risk, thus enabling early preventive action.
“We were inspired by the growth and weight charts used in paediatrics, which intuitively help clinicians identify children at risk of obesity or undergrowth,” says the first author of the study, Yuanhang Yang, Postdoctoral Researcher at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.
A web-based calculator
The researchers have made their eGFR distribution charts openly available to healthcare professionals and developed a web-based calculator, developed by PhD student Antoine Creon, that can help assess how a patient’s eGFR compares with population norms for their age.
The study included over 1.1 million adults in the region of Stockholm, covering roughly 80 per cent of the population aged between 40 and 100 years. Nearly seven million eGFR tests collected between 2006 and 2021 were used to construct age- and sex-specific distributions.
The findings show that departures from the median eGFR for one’s age and sex are associated with worse outcomes. Individuals with an eGFR below the 25th percentile had a markedly higher risk of developing kidney failure requiring dialysis or transplantation. Mortality also displayed a U-shaped relationship; both low and high percentile extremes were linked to increased risk of death.
Ability to act earlier
The study also illustrates this lack of awareness in healthcare, according to the researchers. Among those with a seemingly normal eGFR above 60 ml/min/1.73 m², but below the 25th percentile, only one fourth had received additional testing for urinary albumin, which is important for detecting early kidney damage.
“For example, consider a 55-year-old woman with an eGFR of 80. Most clinicians would not react to such a seemingly normal value. However, our charts show that this corresponds to the 10th percentile for women of that age – and that she has a three-fold higher risk of starting dialysis in the future. This signals an opportunity to act earlier,” says Juan Jesús Carrero, Professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
A mismatch between two common tests for kidney function may indicate a higher risk for kidney failure, heart disease, and death, a new study shows.
Healthcare providers for decades have measured blood levels of creatinine to track the rate at which kidneys filter waste from muscle breakdown in the bloodstream. According to more recent guidelines, levels of cystatin C, a small protein made by all cells in the body, can also be used to measure kidney function. Since these two tests are influenced by different factors – including some related to disease or aging – using both markers together can provide a better measure of kidney function and risk of organ failure than either one alone.
Led by NYU Langone Health researchers, the new work reveals that many people, especially those who are sick, often have a large gap between the two readings, which may be a signal of future disease. Specifically, the global study shows that more than a third of hospitalised participants had a cystatin C-based readout of kidney function that was at least 30% lower than one based on their creatinine levels.
“Our findings highlight the importance of measuring both creatinine and cystatin C to gain a true understanding of how well the kidneys are working, particularly among older and sicker adults,” said study co-corresponding author Morgan Grams, MD, PhD. “Evaluating both biomarkers may identify far more people with poor kidney function, and earlier in the disease process, by covering the blind spots that go with either test.”
Beyond detecting signs of disease, assessing patients’ kidney function is important for calculating the appropriate dosage for cancer medicines, antibiotics, and many other drugs, says Dr Grams, Professor of Medicine at the NYU Grossman School of Medicine.
During another investigation, the results of which were published the same day, the same research team found that a record number of people worldwide have chronic kidney disease, which is now the ninth leading cause of death globally. Having new ways to spot the condition early can help ensure that patients receive swift treatment and avoid more-dramatic interventions such as dialysis and organ transplantation, says Dr Grams.
For the recent investigation, the research team analysed healthcare records, blood tests, and demographic data collected from 860, 66 men and women of a half-dozen nationalities. All participants had their creatinine and cystatin C levels measured on the same day and received follow-ups 11 years later, on average. The team considered factors unrelated to kidney function that influence the biomarkers’ readings, such as smoking, obesity, and history of cancer.
Performed as part of the international Chronic Kidney Disease Prognosis Consortium, the study is the largest to date to explore differences between the two tests and whether they may signal potential health problems, the authors say. Established to better understand and treat the condition, the consortium provides evidence for global definitions of chronic kidney disease and related health risks.
According to the new findings, those whose cystatin C-based measures of kidney filtration were at least 30% lower than their creatinine-based measures were at higher risk for death, heart disease, and heart failure than those who had a smaller difference between the two metrics. The former group was also more likely to be diagnosed with severe chronic kidney disease that required dialysis or an organ transplant. The same was found for 11% of outpatients and seemingly healthy volunteers.
Dr. Grams notes that while cystatin C testing was first recommended in 2012 by the international organization Kidney Disease—Improving Global Outcomes, a 2019 survey revealed that less than 10 percent of clinical laboratories in the United States performed it in-house. The two largest laboratories, Quest Diagnostics and Labcorp, now offer the test.
“These results underscore the need for physicians to take advantage of the fact that more hospitals and healthcare providers are starting to offer cystatin C testing,” said study co-corresponding author Josef Coresh, MD, PhD, director of NYU Langone’s Optimal Aging Institute. “Physicians might otherwise miss out on valuable information about their patients’ wellbeing and future medical concerns.”
Dr Coresh cautions that among the hospitalised Americans in the study, less than 1% were tested for cystatin C.
A new gene therapy approach aimed at protecting people with type 1 diabetes from developing diabetic kidney disease – a serious and common complication of the condition, has shown promising results in a University of Bristol study.
One in three people with type one diabetes will develop kidney damage during their lifetime, which can develop silently over many years, often going undetected until it becomes severe.
Current treatments can slow kidney damage but there are none that act on the root cause: a tiny filter called the glomerulus. A new study published in Molecular Therapy, demonstrated a 64% reduction in a damage indicator for kidney disease, paving the way for a potential new treatment.
The study, driven by first author, Dr Aldara Martin Alonso and led by Dr Rebecca Foster, Associate Professor of Microvascular Medicine at Bristol Medical School: Translational Health Sciences, explored the potential of delivering a protein called VEGF-C directly into kidney cells.
Previous studies have shown VEGFC could protect against kidney disease as it helps keeps blood vessels in the kidney filter healthy, repairing early signs of diabetes-related kidney damage.
To test whether this new approach could be used to treat or slow down kidney disease, the team used a harmless virus to deliver VEGF-C directly into the kidney cells of diabetic mice.
Their results showed that this approach not only helped the kidneys work better, but also protected a key part of the kidney filter that normally helps prevent damage. It led to a 64% reduction in albuminuria. Importantly, this reduction is more than twice the reduction recommended by the American Diabetes Association to slow the progression of chronic kidney disease.
Dr Foster, the study’s senior author, explained: “Currently, there are no drugs specifically available to protect people with type 1 diabetes from kidney disease, despite their higher risk of developing kidney disease. This gap in treatment highlights the urgent need for new therapeutic approaches. Our goal was to investigate whether gene therapy could offer a viable solution by delivering VEGFC in a more targeted way.”
Dr Foster added: “This gene therapy approach has not been explored before in pre-clinical models and offers a long-term solution for these patients who are at risk of developing kidney disease.”
