Tag: Chronic Kidney Disease

Focusing on rare conditions could reduce kidney disease burden

[ad_1]

Focusing on rare conditions could significantly reduce the burden of kidney disease on both patients and the NHS, according to a major new study led by UCL and the UK Kidney Association.

The study, published in The Lancet to mark World Kidney Day, draws on the largest rare kidney disease dataset ever created. It found that patients with rare kidney diseases are 28 times more likely to experience kidney failure than those with chronic kidney disease (CKD), but are less than half as likely to die before kidney failure treatment is needed.

The results suggest that additional focus on treating rare kidney diseases, many of which have new therapies in development or already available, could disproportionately alleviate the overall demand for expensive and hazardous dialysis and kidney transplantation treatments. The authors hope that the research will reframe perceptions of chronic kidney disease, rare diseases and kidney failure among patients, caregivers, regulators, healthcare providers, and researchers.

Chronic kidney disease (CKD) ranges from mild loss of kidney function to kidney failure with around 6% of the general population having mild to moderate CKD – most often caused by poorly controlled blood pressure or diabetes.

Rare kidney diseases are a group of conditions that each affect fewer than one in 2,000 people. Though each disease might be rare on its own, collectively their impact is significant. Rare kidney diseases account for 5-10% of people with CKD, but they constitute over a quarter of those receiving dialysis or with a kidney transplant globally.

To find out what happens to people with these difficult-to-study disorders, the UK’s National Registry of Rare Kidney Diseases (RaDaR) was set up in 2010. It continues to be developed and run by the UK Kidney Association and now includes over 25,000 patients with rare kidney diseases recruited from 108 UK hospitals.

In this study, researchers from UCL and the UK Kidney Association charted the progression and outcomes in 28 rare kidney diseases by comparing data from 27,285 RaDaR patients with data from 2.81 million CKD patients in the general population.

They found that over five years, rare kidney disease patients were 28 times more likely to experience kidney failure compared to CKD patients, yet their overall risk of death was less than half.

Professor Danny Gale, senior author of the study from UCL Division of Medicine and Director of RaDaR, said: “This study underscores the importance of recognizing the pivotal role rare kidney diseases play in the overall burden of kidney failure. Our results show that rare diseases can progress from mild kidney damage to kidney failure so rapidly that, despite being rare in the population, they make a major contribution to the overall burden of kidney failure. This means that therapies effective in these diseases are likely to have a disproportionately beneficial impact on the overall demand for life-sustaining dialysis and kidney transplantation.

“I hope that this will be a call to arms to show how important rare kidney diseases are and the many potential benefits of focusing on these conditions. Treatments for many of these diseases are either available or in development, so I think we now have a golden opportunity to substantially reduce the burden, both for patients and the NHS, of kidney failure.”

The authors say that the results are likely to reframe perceptions of chronic kidney disease, rare diseases and kidney failure among regulators, healthcare providers and researchers.

In general, rare kidney disease patients are much younger than those with CKD and are much less likely to die from related conditions such as cardiovascular disease. We know that they can live a long life with a successful kidney transplant, but there’s also an opportunity to prevent kidney failure in the first place with targeted treatment. I hope that the robust, large-scale data for each of the 28 diseases covered by RaDaR will inform trial design and make developing new treatments a less uncertain endeavor for drug companies.”

Dr Katie Wong, first author of the study from UCL Division of Medicine and RaDaR Clinical Research Fellow at the UK Renal Registry

As well as the difference new treatments would make to patients’ lives, reducing the burden of kidney failure could bring significant cost and resource savings. Kidney failure alone accounts for around 3% of the NHS’s budget, with dialysis costing £30-40,000 per person each year. Currently, around 70,000 people receive kidney replacement therapy in the UK, with around 45% on dialysis and 55% with functioning kidney transplants.

Ron Cullen, Chief Executive of the UK Kidney Association, said: “Since its inception some 13 years ago, the National Registry of Rare Kidney Diseases (RaDaR) has been a key strategic development led by the UK Kidney Association and the renal community. It is now the largest rare kidney disease registry in the world and its continuous growth and evolution make it an invaluable resource.

“With a strengthening connection between the medical community and patients with rare kidney diseases, RaDaR offers insights that are crucial for shaping future research and clinical discoveries. It is wonderful to see all the hard work of so many individuals come to fruition in a paper that could have significant patient benefit.”

Elaine Davies, Director of Research Operations at Kidney Research UK said: “As well as highlighting the importance of finding treatments for rare kidney diseases, these new results will allow patients and doctors to make more informed decisions about their care and will be invaluable for the planning of future clinical trials. RaDaR is a fantastic resource that has provided and will continue to offer vital insights into rare kidney diseases, and we are proud to support it.”

RaDaR, originally funded by the Medical Research Council, Kidney Research UK, Kidney Care UK and the Polycystic Kidney Disease Charity, is now managed and funded by the UK Kidney Association.

Source:

University College London

Journal reference:

Wong, K., et al. (2024). Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort. The Lancet. doi.org/10.1016/s0140-6736(23)02843-x.

[ad_2]

Source link

March 15, 2024
New research identifies potential drug target to prevent kidney failure

[ad_1]

A new study found that retinoic acid receptors (RARa) in the proximal tubules of the kidney play a crucial role in limiting the damaging effects of kidney injury that often lead to kidney failure. Researchers from Weill Cornell Medicine have developed a preclinical model that showed a condition like chronic kidney disease develops when RARa in proximal tubules stop working.

Currently, there are few drugs on the market, so patients with prolonged, untreated kidney disease must undergo dialysis or kidney replacement. The paper, published in PNAS on Feb. 8, suggests drugs that can activate RARa in the kidney could counteract fibrosis—the buildup of scar tissue that results from inflammation caused by diabetes, autoimmune diseases or viral infections like COVID-19—to treat kidney disease.

Our kidneys filter blood to remove waste, which is excreted in urine. Proximal tubules are an important part of this process and return the substances needed by the body back into the blood. The RARa help maintain the health of proximal tubules and keep the kidneys working.

When RARa is knocked out in the proximal tubules of their mouse model, the researchers discovered that within three days mitochondria that produce energy in cells become distressed and cells start dying. After three months, they observed that epithelial cells in the proximal tubule secreted growth factors that led to fibrosis and decreased levels of retinoic acid, which normally binds to the RARa.

Stopping progressive renal fibrosis, a hallmark of late-stage chronic kidney disease, would be one way to prevent kidney failure. The researchers hope to use their novel mouse model to identify drugs that activate RARa to slow or reverse fibrosis and to potentially return kidneys to a healthy state.

Source:

Journal reference:

DiKun, K. M., et al. (2024) Retinoic acid receptor α activity in proximal tubules prevents kidney injury and fibrosis. Proceedings of the National Academy of Sciences of the United States of America. doi.org/10.1073/pnas.2311803121.

[ad_2]

Source link

March 9, 2024
Chronic underhydration linked to major health risks, study finds

[ad_1]

In a recent review article published in the journal Nature Reviews Nephrology, researchers synthesized what is known about the long-term consequences of being chronically underhydrated.

Most people know hydration is vital to staying healthy, but surveys suggest that underhydration is a common problem affecting nearly half of surveyed adults in the United States and Europe. Experts believe it to be exacerbated by the lack of inclusion in health guidelines and reinforcement by doctors during preventive check-ups.

While the effects of acute dehydration in the short term are widely known, less clinical focus has been given to the long-term effects of chronic underhydration.

Epidemiological studies now suggest that even mild but chronic underhydration can lead to the development of coronary heart disease, heart failure, diabetes, obesity, kidney function deterioration, premature mortality, and faster aging. These findings have been strengthened by observing mice subjected to chronic water restriction.

Review: Long-term health outcomes associated with hydration status. Image Credit: Love the wind / Shutterstock

Adaptive responses to underhydration

Homeostasis is the state of balance among all the body systems needed for the body to survive and function correctly, and water balance is a key mechanism through which this happens. Osmoregulation, or the control of water and salt balance, is known to provide an osmotically stable environment for many cells.

Underhydration leads to adaptive changes across the body. At all times, water losses through respiration, the gastrointestinal tract, sweat, and urine must be matched by water gains through ingestion of food and liquids.

The body needs to maintain a stable composition and volume of intracellular fluids (ICF) and extracellular fluids (ECF); changes in the body’s water content, either because of a surplus or a deficit, affect all organs, tissues, and cells.

One response to a water balance deficit is the release of the antidiuretic hormone arginine vasopressin (AVP), which decreases water loss through excretion. Vasoconstriction, blood pressure stabilization, and increased heart rate occur while water reabsorption is facilitated.

The sensations of thirst and appetite for salt are also stimulated by AVP and angiotensin II (ANGII). However, thirst regulation or anticipatory inhibition operates to prevent overdrinking; thirst responses may also decline with age. Sweating is also attenuated, which can lead to compromised thermoregulatory responses in sweltering conditions and cause chronic kidney disease.

Over time, chronic underhydration may establish a new water balance steady state, matching water losses with water intake. This response may be triggered under conditions where access to water is limited. Over time, this could lead to the deterioration of physiological systems, but these mechanisms are poorly understood.

Diseases associated with underhydration

Researchers consider underhydration or hypohydration to be a moderate decrease in the body’s water levels that leads to water conservation mechanisms being activated so that normal levels of plasma osmolality and sodium can be maintained. This contrasts with dehydration, a state in which the water conservation mechanisms cannot maintain water balance.

Acute water loss is most visible in military personnel and athletes, increasing heart rate and reducing anaerobic exercise performance. Acute dehydration can also adversely affect cognitive functioning, including alertness, concentration, short-term memory, and visual perception.

Certain diseases and conditions are thought to predispose people to underhydration. For example, uncontrolled diabetes mellitus can lead to water loss because it reduces renal water reabsorption. Increased urine output can result from nephrogenic diabetes insipidus and some forms of polycystic kidney disease. Conversely, certain cancers and drugs can also stimulate AVP secretion without low water intake, leading to hyponatremia.

Interventions to increase hydration

In response to emerging evidence regarding the adverse effects of underhydration, researchers have begun to explore whether optimal hydration can prevent or slow metabolic and cardiovascular diseases.

Interventions that focused on regimens designed to increase water intake found that participants faced barriers such as forgetting to drink, lack of access, lack of thirst, dislike for the taste of water, and not appreciating the benefits of proper hydration; another issue was work-related disruptions resulting from an increased frequency of urination.

These challenges were demonstrated by an experiment that found lower adherence to water intake regimens compared to a control liquid of inactive syrup.

One trial that successfully increased hydration in the intervention group found that higher water intake was significantly associated with reduced copeptin levels among people with chronic kidney disease. Another found that the greatest changes were seen in people who were habitually low drinkers.

Conclusions

The literature identifies connections between chronic underhydration markers and a heightened risk of several chronic diseases, but the mechanisms underlying these phenomena are not well understood. There are indications that hydration could be a preventive tool, but causal inference has been limited by the lack of adherence to hydration regimens.

However, even with these limitations, there is evidence that optimal hydration can be beneficial for people who are habitually low drinkers. Future studies on the efficacy of interventions to increase water intake should monitor compliance more closely and continue to focus on chronically underhydrated populations who stand to gain the most.

[ad_2]

Source link

February 28, 2024
Evaluating a machine learning tool for predicting hospital-acquired acute kidney injury

[ad_1]

Hospital-acquired acute kidney injury (HA-AKI) is a common complication in hospitalized patients that can lead to chronic kidney disease and is associated with longer hospital stays, higher health care costs and increased mortality. Given these negative consequences, preventing HA-AKI can improve hospitalized patient outcomes. However, anticipating HA-AKI onset is difficult due to a large number of contributing factors involved.

Researchers from Mass General Brigham Digital tested a commercial machine learning tool, the Epic Risk of HA-AKI predictive model, and found it was moderately successful at predicting risk of HA-AKI in recorded patient data. The study found a lower performance than those recorded by Epic Systems Corporation’s internal validation, highlighting the importance of validating AI models before clinical implementation.

The Epic model works by assessing adult inpatient encounters for the risk of HA-AKI, marked by predefined increases in serum creatinine levels. After training the model using data from MGB hospitals, the researchers tested it on data from nearly 40,000 inpatient hospital stays for a five-month period between August 2022 and January 2023. The dataset was extensive with many points collected on patient encounters, including information such as patient demographics, comorbidities, principal diagnoses, serum creatinine levels and length of hospital stay. Two analyses were completed looking at encounter-level and prediction-level model performance.

The investigators observed that the tool was more reliable when assessing patients with lower risk of HA-AKI. Although the model could confidently identify which low-risk patients would not develop HA-AKI, it struggled to predict when higher-risk patients might develop HA-AKI. Results also varied depending on the stage of HA-AKI being evaluated -;predictions were more successful for Stage 1 HA-AKI compared to more severe cases.

The authors concluded overall that implementation may result in high false-positive rates and called for further study of the tool’s clinical impact.

We found that the Epic predictive model was better at ruling out low-risk patients than identifying high-risk patients. Identifying HA-AKI risk with predictive models could help support clinical decisions such as by warning providers against ordering nephrotoxic medications, but further study is needed before clinical implementation.”

Sayon Dutta, MD, MPH, lead study author of Mass General Brigham Digital’s Clinical Informatics team, and emergency medicine physician at Massachusetts General Hospital

Source:

Journal reference:

Dutta, S., et al. (2024). External Validation of a Commercial Acute Kidney Injury Predictive Model. NEJM AI. doi.org/10.1056/aioa2300099.

[ad_2]

Source link

February 17, 2024
Moderate kimchi intake linked to lower obesity rates, study shows
[ad_1]
In a recent study published in the journal BMJ Open, researchers explored the relationship between kimchi consumption and obesity in South Korea.

Study: Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study. Image Credit: Nungning20/Shutterstock.com

Obesity is associated with nutritional, environmental, and lifestyle factors and is a significant risk factor for diabetes, chronic kidney disease, cardiovascular disease, and hyperlipidemia. Obesity prevalence in South Korea has increased steadily over the years. Meanwhile, the prevalence of abdominal obesity has also increased over time.

Increased obesity prevalence is associated with higher medical expenditure; thus, obesity prevention remains a public health priority. In Korea, kimchi is a traditional side dish low in calories but rich in vitamins, dietary fiber, polyphenols, and lactic acid bacteria. There are concerns about kimchi as one of the major contributors to sodium intake.

A 2019-20 survey revealed that daily sodium intake from kimchi was 500 mg (15% of total sodium intake). Studies have shown associations between increased sodium intake and a greater prevalence of hypertension and obesity. Nevertheless, consuming fermented vegetables and kimchi has been associated with lower body weight and improved total cholesterol and fasting blood glucose levels.

About the study

The present study explored the associations between kimchi consumption and obesity in South Korean adults. The researchers used data from a large, prospective, community-based cohort study, “Health Examinees” (HEXA). HEXA was part of a larger genome and epidemiology study examining genetic and environmental risk factors for chronic diseases in adults aged > 40.

Baseline assessments in the HEXA study were performed between 2004 and 2013. Participants were excluded if they had a history of cancer, cerebrovascular disease, diabetes, cardiovascular disease, hyperlipidemia, or hypertension. Those with an implausible energy intake and missing anthropometric data were also excluded.

A semi-quantitative food frequency questionnaire assessed dietary intake for the past year. Total kimchi included kkakdugi, dongchimi (watery kimchi), baechu kimchi (cabbage kimchi), and others, e.g., mustard green kimchi, lettuce kimchi, and green onion kimchi. Intake of sodium, potassium, macronutrients, and fiber was calculated. Obesity is having a body mass index (BMI) ≥ 25 kg/m².

Abdominal obesity was defined as having a waist circumference (WC) ≥ 90 cm for males and ≥ 85 cm for females. A questionnaire was administered to capture data on sociodemographics, smoking, disease history, menopause status, and physical activity.

Participants were stratified into groups based on kimchi intake. A multivariable logistic analysis estimated odds ratios and 95% confidence intervals of obesity by kimchi intake.

Findings

The study included 115,726 individuals aged 51.8, on average. Most participants (> 68%) were female. Obesity prevalence was 28.2% overall, 24.7% in females, and 36.1% in males. Individuals consuming five or more servings/day of total kimchi had increased weight and WC compared to those consuming less than one serving per day; they were also more likely to consume alcohol and be obese.

Males with ≥ five servings/day of total kimchi were younger, smokers, taller, and more physically active than those with less than one serving/day. By contrast, females consuming ≥ five servings per day were older, non-smokers, physically inactive, post-menopausal, shorter, and married compared to those consuming less than one serving a day.

Males consuming up to three servings of total kimchi daily had a lower obesity prevalence than those consuming less than one serving a day. Baechu kimchi consumption (≥ three servings/day) among males was significantly associated with a 10% reduced prevalence of obesity and abdominal obesity relative to those with less than one serving/day.

In females, two to three servings per day of baechu consumption was associated with about 8% lower obesity prevalence and 6% lower prevalence of abdominal obesity compared to those with less than one serving/day. Individuals consuming kkakdugi more than the median quantity had lower odds of having abdominal obesity compared to non-consumers.

Conclusions

Overall, the study illustrated an inverse association between total kimchi consumption (one to three servings per day) and obesity risk in males. In addition, males with a higher intake of baechu kimchi had a lower prevalence of abdominal obesity and obesity. Increased kkakdugi intake was associated with lower abdominal obesity prevalence in both males and females.

While consuming five or more servings of kimchi was associated with higher obesity prevalence, it was not statistically significant. Higher total kimchi intake was also associated with increased protein, carbohydrates, fat, sodium, cooked rice, and total energy intake. The study’s limitations include its cross-sectional design, which limits causal inference, and lack of generalizability to other populations.
Journal reference:

Jung H, Yun Y, Hong SW, et al. (2024). Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study. BMJ Open. doi: 10.1136/bmjopen-2023-076650. https://bmjopen.bmj.com/content/14/2/e076650
[ad_2]

Source link
February 4, 2024