The cookbook introduces a variety of culturally diverse kidney-friendly recipes that kids of all ages love.
It has been one year since the Children’s National Hospital Department of Nephrology released their cookbook “Keeping it Renal: Global Cuisine for Kids” and we are still receiving requests for this collection of recipes. In order to stay healthy, most children with kidney disease have to limit or avoid foods that are high in certain minerals including sodium, potassium and phosphorus. “Children on dialysis have to give up a lot of what they like to eat. This cookbook introduces a variety of culturally diverse kidney-friendly recipes that kids of all ages love. By learning to cook these recipes, our patients can take an active role in their own healthcare and learn some fun new skills,” said Kristen Sgambat, Ph.D., R.D., and Asha Moudgil, M.D., medical director of transplant.
It is often challenging for children and their families to balance these dietary restrictions with proper nutrition and enjoyable mealtimes. “This cookbook offers novel and exciting recipes that patients and families may not be aware of. Seeing these options can help patients see that a renal diet does not have to be bland or repetitive and thus improve patients’ outlook on treatment and motivate them to adhere to the dietary restrictions,” said Kaushalendra Amatya, Ph.D., pediatric psychologist for Nephrology and Cardiology at Children’s National.
As an innovative way to facilitate adherence to these limitations, our nephrology department collaborated with our patient families to create the cookbook “Keeping it Renal: Global Cuisine for Kids,” a compilation of their favorite kidney-friendly recipes.
Children’s National is one of the top pediatric hospitals in NIH funding, and our nephrology program ranks number 7 in the country, according to U.S. News & World Report. The Kidney Transplantation Program is the only one of its kind in the Washington, D.C., area focused on the needs of children and teens with kidney disease. Committed to providing the best quality care to all of our pediatric dialysis and transplant patients, we are always looking for new ways to support our patient families.
If you would like to receive a copy of the Keeping it Renal: Global Cuisine for Kids cookbook, please send your request to: emorrow@childrensnational.org.
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“These physicians are incredible additions to our nephrology division,” said Marva Moxey-Mims, M.D., chief of the Division of Nephrology at Children’s National. “We are excited about the expertise these young physicians already contribute to our division and can’t wait to share more as we continue to expand our efforts as one of the top nephrology programs in the country. We are elated to have them on our team.”
Each of the new faculty members has specific areas of clinical and research interests. Dr. Brown’s focus is chronic kidney disease (CKD) and the impact of acidosis on growth and disease progression. Dr. Brunson’s interest is dialysis, health disparities and social determinants of health for children with CKD. She is a JELF Advocacy scholar through the American Society of Nephrology. Dr. Gulati is an expert in inherited kidney diseases with a particular focus on polycystic kidney disease for which she has external grant support. Dr. Meyers’ interest is kidney transplantation and Dr. Park, our newest addition, is interested in systemic inflammatory diseases, especially lupus nephritis.
The nephrology team will continue to provide comprehensive inpatient and outpatient care to children throughout the full spectrum of kidney diseases.
Denver Brown, M.D., Celina Brunson, M.D., Ashima Gulati, M.D., Melissa Meyers, M.D. and Catherine Park, M.D., recently joined the nephrology division.
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Wilms tumor is a rare kidney cancer that primarily affects children. Also known as nephroblastoma, it is the most common malignant renal tumor in children. Advances in the treatment of Wilms tumor are some of the great achievements in the field of oncology, improving survival to 90% and decreasing the burden of therapy.
A key factor in the success of Wilms tumor treatment has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient’s risk of relapse. In a review article in Current Opinion in Pediatrics, Jeffrey Dome, M.D., Ph.D., vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, Marie V. Nelson, M.D., assistant professor of pediatrics in the Division of Oncology, and their colleagues look at the evolution of clinical and biological factors that have been adopted for Wilms tumor.
The authors found that the original National Wilms Tumor Study Group (NWTSG) and International Society of Pediatric Oncology (SIOP) studies relied solely on tumor stage to define treatment. Over time, however, additional factors were incorporated into the risk stratification schema, allowing for a multifactorial precision medicine approach.
The authors conclude that “the application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.”
While much has been written about advances in the field of pediatric transplantation, there have been relatively few publications that address the social, psychological and day‐to‐day struggles faced by pediatric transplant recipients and their families. A special February 2021 issue of the journal Pediatric Transplantation, guest edited by Children’s National Hospital nephrologist and medical director of transplant Asha Moudgil, M.D., features a compilation of articles from a diverse group of professionals who share their expertise on topics related to healthy living for pediatric solid organ transplant patients. Among these leaders in their fields are several clinicians from Children’s National, including Jonathan Albert, M.D. (Infectious Diseases fellow), Benjamin Hanisch, M.D. (Transplant Infectious Diseases), Kristen Sgambat, Ph.D., R.D. (Renal Dietician), Melissa R. Meyers, M.D. (Nephrologist) and Kaushalendra Amatya, Ph.D. (Psychologist).
In an editorial co-written with Priya Verghese, M.D., of Ann & Robert H. Lurie Children’s Hospital of Chicago, Dr. Moudgil writes, “It is widely acknowledged by those practicing in the field of transplant medicine that taking care of pediatric transplant recipients is a complex endeavor for all parties involved, including patients, families, and providers. In this compendium, we bring you expertise from a diverse group of professionals — including physicians, psychologists, social workers, and nutritionists. These authors provide a concise summary of the literature and evidence when available, and offer personal insight where there is paucity of literature in topics related to healthy living in pediatric transplantation.”
Dr. Albert, Dr. Hanisch and Sgambat provide their expertise in an article titled “Approaches to safe living and diet after solid organ transplantation,” which reviews the risks that pediatric and adolescent solid organ transplant recipients encounter through exposures such as household contacts, outdoor activities, travel, animal exposures and dietary choices.
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In a recent study, Asha Moudgil, M.D., and colleagues looked at differences in socioeconomic factors and subclinical cardiovascular disease markers by race in chronic kidney disease patients.
Children with chronic kidney disease (CKD) are known to have an increased risk for cardiovascular (CV) disease. African American children with CKD are also disproportionately affected by socioeconomic disadvantages related to systemic racism.
In a recent analysis of 3,103 visits from 628 children enrolled in the Chronic Kidney Disease in Children (CKiD) study, Children’s National Hospital researchers Kristen Sgambat, Ph.D., and Asha Moudgil, M.D., and their colleagues found that African American children with CKD had increased left ventricular mass index, more ambulatory hypertension and differences in lipid profile compared with Caucasian children. After adjusting for socioeconomic factors (public health insurance, household income, maternal education, food insecurity, abnormal birth history), a trend towards attenuation of the differences in these CV markers was observed.
The authors of the study conclude that, “as many social determinants of health were not captured by our study, future research should examine effects of systemic racism on CV health in this population.”
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A first-of-its-kind study demonstrated that IV carnitine supplementation is associated with improvement in myocardial strain and repletion of plasma total and free carnitine in children with AKI receiving CRRT.
Supplementation of a special nutrient could help improve heart function in children receiving continuous dialysis in critical care units. The nutrient carnitine plays an essential role in producing energy for use by heart and skeletal muscles. Critically ill children with acute kidney dysfunction often need a continuous dialysis therapy (also known as CRRT, continuous renal replacement therapy) to help remove toxins while kidneys are not working. An unintended consequence of this CRRT is removal of carnitine. Often these critically ill children are unable to eat by mouth and therefore can’t receive carnitine unless it is supplemented. Children’s National Hospital researchers have proven that intravenous carnitine supplementation is associated with repletion of the body’s carnitine supply and may cause improvement in heart function as shown by heart strain analysis (which detects subclinical cardiac dysfunction that may not be apparent by traditional echocardiography).
In a first-of-its-kind study, the Children’s National researchers, Asha Moudgil, M.D., Kristen Sgambat, M.D., and Sarah Clauss, M.D., investigated carnitine deficiency in children receiving CRRT. They demonstrated for the first time that these children become severely deficient in carnitine after being on CRRT for >1 week, and that carnitine supplementation is associated with carnitine repletion and improved heart function. This knowledge can help to guide clinical care, as carnitine can be easily added to the IV nutritional formulations that are typically given to these patients.
Although little was previously known about carnitine status in patients with acute kidney injury (AKI) receiving CRRT, iatrogenic carnitine deficiency related to chronic hemodialysis (HD) in patients with end stage renal disease is a well-known phenomenon. It was theorized that given the continuous removal of solutes by CRRT in combination with lack of dietary intake and impaired production of endogenous carnitine by the kidney in critically ill children with AKI, carnitine would be rapidly depleted.
The latest controlled pilot study (NCT01941823) of 48 children hypothesized that carnitine supplementation would improve left ventricular function in children receiving CRRT. Children ages 1-21 years with AKI requiring CRRT, who were admitted to the pediatric intensive care unit at Children’s National Hospital from 2015 to 2018 were eligible to prospectively enroll in the “CRRT Intervention group,” if they were total parenteral nutrition (TPN)-dependent and not receiving any enteral or IV carnitine prior to enrollment.
The researchers say that “An exciting collaborative effort between nephrology and cardiology made it possible to use a sophisticated technology known as speckle tracking imaging to study the effects of carnitine on heart in this population.” This technology can identify early changes in heart motion, also known as cardiac strain that may not be detected using standard heart imaging techniques.
This is the first study to demonstrate that IV carnitine supplementation is associated with improvement in myocardial strain and repletion of plasma total and free carnitine in children with AKI receiving CRRT. A cohort of pediatric chronic HD patients demonstrated similar benefits in a prior study conducted by Drs. Moudgil and Sgambat. Compared with chronic HD, carnitine is even more rapidly depleted by CRRT, with losses approximating 80% of intake. The effect of carnitine deficiency and supplementation on cardiovascular function in patients receiving CRRT had not been previously investigated.
The pilot study by Drs. Moudgil, Sgambat, and Clauss was single center and limited by small sample size. The small sample size may have limited the ability to detect significant differences in demographics and clinical characteristics and multivariable analyses could not be performed. However, given that it is a pilot study, the findings provide a solid launching point for future investigations to show how supplementation can be best utilized to optimize cardiac outcomes in children receiving CRRT.
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“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”
Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.
“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”
Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:
Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.
“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”
Read more about Dr. Beer’s career and appointment as president of the AAP.
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Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus.
Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus. The campus, now under construction, is being developed on nearly 12 acres of the former Walter Reed Army Medical Center. Children’s National will name the main auditorium in recognition of Boeing’s generosity.
“We are deeply grateful to Boeing for their support and commitment to improving the health and well-being of children in our community and around the globe,” said Kurt Newman, M.D., president and CEO of Children’s National “The Boeing Auditorium will help the Children’s National Research & Innovation campus become the destination for discussion about how to best address the next big healthcare challenges facing children and families.”
The one-of-a-kind pediatric hub will bring together public and private partners for unprecedented collaborations. It will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.
“Children’s National Hospital’s enduring mission of positively impacting the lives of our youngest community members is especially important today,” said Boeing President and CEO David Calhoun. “We’re honored to join other national and community partners to advance this work through the establishment of their Research & Innovation Campus.”
Children’s National Research & Innovation Campus partners currently include Johnson & Johnson Innovation – JLABS, Virginia Tech, the National Institutes of Health (NIH), Food & Drug Administration (FDA), U.S. Biomedical Advanced Research and Development Authority (BARDA), Cerner, Amazon Web Services, Microsoft, National Organization of Rare Diseases (NORD) and local government.
The 3,200 square-foot Boeing Auditorium will be the focal point of the state-of-the-art conference center on campus. Nationally renowned experts will convene with scientists, medical leaders and diplomats from around the world to foster collaborations that spur progress and disseminate findings.
Boeing’s $5 million commitment deepens its longstanding partnership with Children’s National. The company has donated nearly $2 million to support pediatric care and research at Children’s National through Chance for Life and the hospital’s annual Children’s Ball. During the coronavirus pandemic, Boeing fabricated and donated 2,000 face shields to help keep patients and frontline care providers at Children’s National safe.
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High magnification micrograph of focal segmental glomerulosclerosis (FSGS).
Reducing the amount of protein in the urine of patients with focal segmental glomerulosclerosis (FSGS), a rare disease in which scar tissue forms on the parts of the kidneys that filter waste from the blood, can significantly slow declines in kidney function and extend time before patients’ kidneys fail, a new analysis by a Children’s National Hospital researcher and her colleagues shows. These findings, published online Aug. 10, 2020, in the American Journal of Kidney Disease, could provide hope for patients who are able to lower their urinary protein with available treatments but aren’t able to achieve complete remission, the researchers say.
FSGS affects about seven per every million people in the general population. However, in the United States, it’s responsible for between 5 and 20% of all cases of end stage kidney disease (ESKD), a condition in which the kidney function declines enough that patients can’t survive without dialysis or a kidney transplant. There are no proven treatments specifically targeting FSGS, but steroids and other immunosuppressants have shown promise in clinical trials.
One characteristic sign of FSGS is proteinuria, in which too much protein is present in patients’ urine. Most clinical trials of FSGS treatments have focused on complete remission of proteinuria as a sign that the intervention is working. However, says Marva Moxey-Mims, M.D., researcher and chief of the Children’s National Division of Nephrology, only a fraction of patients meet that end goal. Instead, many patients achieve some reduction in proteinuria, but it’s been unclear whether those reductions lead to significant benefits for kidney health.
To investigate this question, Dr. Moxey-Mims and her colleagues used data from the National Institutes of Health-funded FSGS clinical trial that took place between November 2004 and May 2008. Participants in this study — 138 patients who developed proteinuria due to FSGS between the ages of 2 and 40 and didn’t respond to steroids — received one of two different immunosuppressant regimens. They received frequent checkups including urinary protein tests during the duration of the study and were followed for a maximum of 54 months.
Results showed that about 49% of the study participants’ proteinuria improved by 26 weeks of treatment on either regimen. More importantly, says Dr. Moxey-Mims, these patients retained significantly better kidney function over time, determined by a test called estimated glomerular filtration rate (eGFR), compared to those whose urinary protein remained high. The greater the reduction in proteinuria, the better their kidney function remained, and the longer their kidneys remained active before they developed ESKD.
“Even a modest reduction in proteinuria, as small as 20 or 30%, had an impact on these patients’ kidney health,” Dr. Moxey-Mims says.
Dr. Moxey-Mims notes that the finding could impact the design of clinical trials for FSGS treatments. Currently, these trials typically must include large numbers of patients to show a benefit if complete remission of proteinuria — which only occurred in about 20% of patients in the National Institute of Diabetes and Digestive and Kidney Diseases trial — is used as the end point.
If researchers use a range of proteinuria reduction as end points, she says, it could be easier to see if a drug or other intervention is working.
Similarly, she says, patients with FSGS and their doctors should view any proteinuria reduction as a positive.
“They shouldn’t be discouraged if they can’t reach full remission,” Dr. Moxey-Mims says. “Doctors and patients alike can feel reassured that if they’re reducing protein in the urine to some degree, then patients are getting some benefit.”
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The UAB/Children’s National grant is a U54 center grant, an NIH funding mechanism to develop a multidisciplinary attack on a specific disease entity or biomedical problem area. With this grant, UAB joins with investigators at the University of Kansas and the University of Maryland-Baltimore as part of the NIH Polycystic Kidney Disease Research Resource Consortium. The NIH describes the consortium as a framework for effective collaboration to develop and share research resources, core services and expertise to support innovation in research related to polycystic kidney disease.
“Infants with childhood cystic kidney disease may develop kidney failure within a few years after birth and some need dialysis and kidney transplantation before they reach adulthood,” said Lisa Guay-Woodford, M.D., director of the Clinical and Translational Science Institute at Children’s National and co-director of the UAB-CCKDCC. “In many cases, the earlier the onset of symptoms, the more severe the outcome.”
“The intent is to accelerate the science and advance research into new therapies for cystic kidney disease through enhanced sharing of resources and the establishment of a robust research community,” said Bradley K. Yoder, Ph.D., professor and chair of the UAB Department of Cell, Developmental and Integrative Biology and co-director of the UAB-CCKDCC. “Childhood polycystic disease can be a devastating condition for children and their families.”
The UAB-CCKDCC will focus primarily on childhood polycystic kidney disease, a condition that affects about one in 20,000 infants in the United States. The center’s primary goals are:
Provide the Polycystic Kidney Disease Research Resource Consortium members with access to phenotypic, genetic and clinical information and biomaterials from CCKD patients
Analyze pathways involved in cyst pathogenesis through the generation of verified genetic model systems and biosensor/reporter systems
Assess the impact of patient variants on cystic disease proteins through generation and validation of innovative models
Provide ready access to biological materials from genetic CCKD models
Develop efficient pipelines for in vitro and in vivo preclinical testing of therapeutic compounds
Dr. Guay-Woodford is an internationally recognized pediatric nephrologist with a research program focused on identifying clinical and genetic factors involved in the pathogenesis of inherited renal disorders, most notably autosomal recessive polycystic kidney disease (ARPKD). Her laboratory has identified the disease-causing genes in several experimental models of recessive polycystic kidney disease and her group participated in the identification of the human ARPKD gene as part of an international consortium. In addition, her laboratory was the first to identify a candidate modifier gene for recessive polycystic kidney disease. For her contributions to the field, she was awarded the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease, given by the Polycystic Kidney Disease Foundation and the International Society of Nephrology.
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Children’s National Hospital in Washington, D.C., was ranked No. 7 nationally in the U.S. News & World Report 2020-21 Best Children’s Hospitals annual rankings. This marks the fourth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide.
In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fourth year in a row.
For the tenth straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.
“Our number one goal is to provide the best care possible to children. Being recognized by U.S. News as one of the best hospitals reflects the strength that comes from putting children and their families first, and we are truly honored,” says Kurt Newman, M.D., president and CEO of Children’s National Hospital.
“This year, the news is especially meaningful, because our teams — like those at hospitals across the country — faced enormous challenges and worked heroically through a global pandemic to deliver excellent care.”
“Even in the midst of a pandemic, children have healthcare needs ranging from routine vaccinations to life-saving surgery and chemotherapy,” said Ben Harder, managing editor and chief of Health Analysis at U.S. News. “The Best Children’s Hospitals rankings are designed to help parents find quality medical care for a sick child and inform families’ conversations with pediatricians.”
The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.
The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.
Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:
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Children’s National Research Institute directors Vittorio Gallo, Ph.D., and Mark Batshaw, M.D.
The Children’s National Research Institute recently released its 2019-2020 academic annual report, titled 150 Years Stronger Through Discovery and Care to mark the hospital’s 150th birthday. Not only does the annual report give an overview of the institute’s research and education efforts, but it also gives a peek in to how the institute has mobilized to address the coronavirus pandemic.
“Our inaugural research program in 1947 began with a budget of less than $10,000 for the study of polio — a pressing health problem for Washington’s children at the time and a pandemic that many of us remember from our own childhoods,” says Vittorio Gallo, Ph.D., chief research officer at Children’s National Hospital and scientific director at Children’s National Research Institute. “Today, our research portfolio has grown to more than $75 million, and our 314 research faculty and their staff are dedicated to finding answers to many of the health challenges in childhood.”
Highlights from the Children’s National Research Institute annual report
In 2018, Children’s National began construction of its new Research & Innovation Campus (CNRIC) on 12 acres of land transferred by the U.S. Army as part of the decommissioning of the former Walter Reed Army Medical Center campus. In 2020, construction on the CNRIC will be complete, and in 2012, the Children’s National Research Institute will begin to transition to the campus.
In late 2019, a team of scientists led by Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, traveled to the Democratic Republic of Congo to collect samples from 60 individuals that will form the basis of a new reference genome data set. The researchers hope their project will generate better reference genome data for diverse populations, starting with those of Central African descent.
A gift of $5.7 million received by the Center for Translational Research’s director, Lisa Guay-Woodford, M.D., will reinforce close collaboration between research and clinical care to improve the care and treatment of children with polycystic kidney disease and other inherited renal disorders.
The Center for Neuroscience Research’s integration into the infrastructure of Children’s National Hospital has created a unique set of opportunities for scientists and clinicians to work together on pressing problems in children’s health.
Children’s National and the National Institute of Allergy and Infectious Diseases are tackling pediatric research across three main areas of mutual interest: primary immune deficiencies, food allergies and post-Lyme disease syndrome. Their shared goal is to conduct clinical and translational research that improves what we know about those conditions and how we care for children who have them.
An immunotherapy trial has allowed a little boy to be a kid again. In the two years since he received cellular immunotherapy, Matthew has shown no signs of a returning tumor — the longest span of time he’s been tumor-free since age 3.
In the past 6 years, the 104 device projects that came through the National Capital Consortium for Pediatric Device Innovation accelerator program raised $148,680,256 in follow-on funding.
Even though he’s watched more than 500 aspiring physicians pass through the Children’s National pediatric residency program, program director Dewesh Agrawal, M.D., still gets teary at every graduation.
Understanding and treating the novel coronavirus (COVID-19)
In a short period of time, Children’s National Research Institute has mobilized its scientists to address COVID-19, focusing on understanding the virus and advancing solutions to ameliorate the impact today and for future generations. Children’s National Research Institute Director Mark Batshaw, M.D., highlighted some of these efforts in the annual report:
Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, is looking at whether or not the microbiome of bacteria in the human nasal tract acts as a defensive shield against COVID-19.
Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research, and her team are seeing if they can “train” T cells to attack the invading coronavirus.
Sarah Mulkey, M.D., Ph.D., an investigator in the Center for Neuroscience Research and the Fetal Medicine Institute, is studying the effects of, and possible interventions for, coronavirus on the developing brain.
You can view the entire Children’s National Research Institute academic annual report online.
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Researchers at Children’s National Hospital are using quantitative imaging and machine intelligence to enhance care for children with a common kidney disease, and their initial results are very promising. Their technique provides an accurate way to predict earlier which children with hydronephrosis will need surgical intervention, simplifying and enhancing their care.
We live in a time of great uncertainty yet great promise, particularly when it comes to harnessing technology to improve lives. Researchers at Children’s National Hospital are using quantitative imaging and machine intelligence to enhance care for children with a common kidney disease, and their initial results are very promising. Their technique provides an accurate way to predict earlier which children with hydronephrosis will need surgical intervention, simplifying and enhancing their care.
Hydronephrosis means “water in the kidney” and is a condition in which a kidney doesn’t empty normally. One of the most frequently detected abnormalities on prenatal ultrasound, hydronephrosis affects up to 4.5% of all pregnancies and is often discovered prenatally or just after birth.
Although hydronephrosis in children sometimes resolves by itself, identifying which kidneys are obstructed and more likely to need intervention isn’t particularly easy. But it is critical. “Children with severe hydronephrosis over long periods of time can start losing kidney function to the point of losing a kidney,” says Marius George Linguraru, DPhil, MA, MSc, principal investigator of the project; director of Precision Medical Imaging Group at the Sheikh Zayed Institute for Pediatric Surgical Innovation; and professor of radiology, pediatrics and biomedical engineering at George Washington University.
Children with hydronephrosis face three levels of examination and intervention: ultrasound, nuclear imaging testing called diuresis renogram and surgery for the critical cases. “What we want to do with this project is stratify kids as early as possible,” Dr. Linguraru says. “The earlier we can predict, the better we can plan the clinical care for these kids.”
Ultrasound is used to see whether there is a blockage and try to determine hydronephrosis severity. “Ultrasound is non-invasive, non-radiating, and does not expose the child to any risk prenatally or postnatally,” Dr. Linguraru says. Ultrasound evaluations require a trained radiologist, but there’s a lot of variability. Radiologists have a grading system based on the ultrasound appearance of the kidney to determine whether the hydronephrosis is mild, moderate or severe, but studies show this isn’t predictive of longer term outcomes.
Children whose ultrasounds show concern will be referred to diuresis renogram. Costly, complex, invasive and irradiating, it tests how well the kidney empties. Although appropriate for good clinical indications, doctors try to minimize its use. “Management of hydronephrosis is complex,” Dr. Linguraru says. “We want to use ultrasound as much as possible and much less diuresis renogram.”
For those patients whose kidney is obstructed and eventually need surgical intervention, the sooner that decision can be made the better. “The more you wait for a kidney that is severely obstructed, the more function may be lost. If intervention is required, it’s preferable to do it early,” Dr. Linguraru says. Of course for the child whose hydronephrosis will likely resolve itself, intervention is not the best option.
“With our technique we are measuring physiological and anatomical changes in the ultrasound image of the kidney,” says Marius George Linguraru, DPhil, MA, MSc. “The human eye may find it difficult to put all this together, but the machine can do it. We use quantitative imaging to do deep phenotyping of the kidney and machine learning to interpret the data.”
Dr. Linguraru and the multidisciplinary team at Children’s National Hospital, including radiology and urology clinicians, are putting the power of computers to work interpreting subtleties in the ultrasound data that humans just can’t see. In their pilot study they found that 60% of the nuclear imaging tests could have been safely avoided without missing any of the critical cases of hydronephrosis. “With our technique we are measuring physiological and anatomical changes in the ultrasound image of the kidney,” Dr. Linguraru says. “The human eye may find it difficult to put all this together, but the machine can do it. We use quantitative imaging to do deep phenotyping of the kidney and machine learning to interpret the data.”
Results of the initial study indicate that kids who have a mild condition can be safely discharged earlier and the model can predict all those kids with obstructions and accelerate their diagnosis by sending them earlier to get further investigation. Dr. Linguraru says. “There are only benefits: some kids will get earlier diagnosis, some earlier discharges.”
The team also has a way to improve the interpretation of diuresis renograms. “We analyze the dynamics of the kidney’s drainage curve in quantifiable way. Using machine learning to interpret those results, we showed we can potentially discharge some kids earlier and accelerate intervention for the most severe cases instead of waiting and repeating the invasive tests,” he says. The framework has 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases, a significant improvement over clinical metrics’ accuracy.
The next step is a study connecting all the protocols. “Right now we have a study on ultrasound, a study on nuclear imaging, but we need to connect them so a child with hydronephrosis immediately benefits,” says Dr. Linguraru. Future work will focus on streamlining and accelerating diagnosis and intervention for kids who need it, both in prospective studies and hopefully clinically as well.
Hydronephrosis is an area in which machine learning can be applied to pediatric health in meaningful ways because of the sheer volume of cases.
“Machine learning algorithms work best when they are trained well on a lot of data,” Dr. Linguraru says. “Often in pediatric conditions, data are sparse because conditions are rare. Hydronephrosis is one of those areas that can really benefit from this new technological development because there is a big volume of patients. We are collecting more data, and we’re becoming smarter with these kinds of algorithms.”
Children with kidney disease have very special diet and nutrition needs. In order to stay healthy, most children with kidney disease have to limit or avoid foods that are high in certain minerals including sodium, potassium and phosphorus. It is often challenging for children and their families to balance following these diet restrictions with getting proper nutrition and enjoying meal times.
As an innovative way to facilitate adherence to these limitations, our nephrology department collaborated with our patient families to create a cookbook “Keeping it Renal: Global Cuisine for Kids,” a compilation of their favorite kidney-friendly recipes.
Children’s National is one of the top pediatric hospitals in NIH funding, and our nephrology program ranks number 6 in the country, according to U.S. News & World Report. The Kidney Transplantation Program is the only one of its kind in the Washington, D.C. area focused on the needs of children and teens with kidney disease. Committed to providing the best quality care to all of our pediatric transplant patients, we are always looking for new ways to support our patient families.
If you would like to receive a copy of the Keeping it Renal: Global Cuisine for Kids cookbook, please send your request via email to: emorrow@childrensnational.org.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2020/02/cooking-in-the-kitchen.png300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2020-02-14 13:38:052020-04-30 16:34:57Keeping it Renal: Global Cuisine for Kids
The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, which makes this organ particularly vulnerable to changes in metabolism.
More than 30 million Americans have diabetes, with the vast majority having Type 2 disease. Characterized by insulin resistance and persistently high blood sugar levels, poorly controlled Type 2 diabetes has a host of well-recognized complications: compared with the general population, a greatly increased risk of kidney disease, vision loss, heart attacks and strokes and lower limb amputations.
But more recently, says Nathan A. Smith, MS, Ph.D., a principal investigator in Children’s National Research Institute’s Center for Neuroscience Research, another consequence has become increasingly apparent. With increasing insulin resistance comes cognitive damage, a factor that contributes significantly to dementia diagnoses as patients age.
The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, Smith explains – which makes this organ particularly vulnerable to changes in metabolism. Type 2 diabetes and even prediabetic changes in glucose metabolism inflict damage upon this organ in mechanisms with dangerous synergy, he adds. Insulin resistance itself stresses brain cells, slowly depriving them of fuel. As blood sugar rises, it also increases inflammation and blocks nitric oxide, which together narrow the brain’s blood vessels while also increasing blood viscosity.
When the brain’s neurons slowly starve, they become increasingly inefficient at doing their job, eventually succumbing to this deprivation. These hits don’t just affect individual cells, Smith adds. They also affect connectivity that spans across the brain, neural networks that are a major focus of his research.
While it’s well established that Type 2 diabetes significantly boosts the risk of cognitive decline, Smith says, it’s been unclear whether this process might be halted or even reversed. It’s this question that forms the basis of a collaborative Frontiers grant, $2.5 million from the National Science Foundation split between his laboratory; the lead institution, Stony Brook University; and Massachusetts General Hospital/Harvard Medical School.
Smith and colleagues at the three institutions are testing whether changing the brain’s fuel source from glucose to ketones – byproducts from fat metabolism – could potentially save neurons and neural networks over time. Ketones already have shown promise for decades in treating some types of epilepsy, a disease that sometimes stems from an imbalance in neuronal excitation and inhibition. When some patients start on a ketogenic diet – an extreme version of a popular fat-based diet – many can significantly decrease or even stop their seizures, bringing their misfiring brain cells back to health.
Principal Investigator Smith and his laboratory at the Children’s National Research Institute are using experimental models to test whether ketones could protect the brain against the ravages of insulin resistance. They’re looking specifically at interneurons, the inhibitory cells of the brain and the most energy demanding. The team is using a technique known as patch clamping to determine how either insulin resistance or insulin resistance in the presence of ketones affect these cells’ ability to fire.
They’re also looking at how calcium ions migrate in and out of the cells’ membranes, a necessary prerequisite for neurons’ electrical activity. Finally, they’re evaluating whether these potential changes to the cells’ electrophysiological properties in turn change how different parts of the brain communicate with each other, potentially restructuring the networks that are vital to every action this organ performs.
Colleagues at Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and Harvard Medical School, led by Principal Investigator Eva-Maria Ratai, Ph.D., will perform parallel work in human subjects. They will use imaging to determine how these two fuel types, glucose or ketones, affect how the brain uses energy and produces the communication molecules known as neurotransmitters. They’re also investigating how these factors might affect the stability of neural networks using techniques that investigate the performance of these networks both while study subjects are at rest and performing a task.
Finally, colleagues at the Laufer Center for Physical and Quantitative Biology at Stony Brook University, led by Principal Investigator Lilianne R. Mujica-Parodi, Ph.D., will use results generated at the other two institutions to construct computational models that can accurately predict how the brain will behave under metabolic stress: how it copes when deprived of fuel and whether it might be able to retain healthy function when its cells receive ketones instead of glucose.
Collectively, Smith says, these results could help retain brain function even under glucose restraints. (For this, the research team owes a special thanks to Mujica-Parodi, who assembled the group to answer this important question, thus underscoring the importance of team science, he adds.)
“By supplying an alternate fuel source, we may eventually be able to preserve the brain even in the face of insulin resistance,” Smith says.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2019/12/brain-network-illustration.png300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2019-12-12 10:58:442022-05-09 15:49:21$2.5M to protect the brain from metabolic insult
Recently, Kurt Newman, M.D., president and CEO of Children’s National Hospital, authored an opinion piece for the popular political website, The Hill. In the article, he called upon stakeholders from across the landscape to address the significant innovation gap in children’s healthcare versus adults.
As Chair of the Board of Trustees of the Children’s Hospital Association, Dr. Newman knows the importance of raising awareness among policy makers at the federal and state level about the healthcare needs of children. Dr. Newman believes that children’s health should be a national priority that is addressed comprehensively. With years of experience as a pediatric surgeon, he is concerned by the major inequities in the advancements of children’s medical devices and technologies versus those for adults. That’s why Children’s National is working to create collaborations, influence policies and facilitate changes that will accelerate the pace of pediatric healthcare innovation for the benefit of children everywhere. One way that the hospital is tackling this challenge is by developing the Children’s National Research & Innovation Campus, which will be the nation’s first innovation campus focused on pediatric research.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2018/02/Kurt-Newman-capitol-building.jpg300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2019-12-11 15:41:002023-07-10 10:07:22Making healthcare innovation for children a priority
Children’s National Hospital and Virginia Tech create formal partnership that includes the launch of a Virginia Tech biomedical research facility within the new Children’s National Research & Innovation Campus.
Children’s National Hospital and Virginia Tech recently announced a formal partnership that will include the launch of a 12,000-square-foot Virginia Tech biomedical research facility within the new Children’s National Research & Innovation Campus. The campus is an expansion of Children’s National that is located on a nearly 12-acre portion of the former Walter Reed Army Medical Center in Washington, D.C. and is set to open its first phase in December 2020. This new collaboration brings together Virginia Tech, a top tier academic research institution, with Children’s National, a U.S. News and World Report top 10 children’s hospital, on what will be the nation’s first innovation campus focused on pediatric research.
“Virginia Tech is an ideal partner to help us deliver on what we promised for the Children’s National Research & Innovation Campus – an ecosystem that enables us to accelerate the translation of potential breakthrough discoveries into new treatments and technologies,” says Kurt Newman, M.D., president and CEO, Children’s National. “Our clinical expertise combined with Virginia Tech’s leadership in engineering and technology, and its growing emphasis on biomedical research, will be a significant advance in developing much needed treatment and cures to save children’s lives.”
Earlier this year, Children’s National announced a collaboration with Johnson & Johnson Innovation LLC to launch JLABS @ Washington, DC at the Research & Innovation Campus. The JLABS @ Washington, DC site will be open to pharmaceutical, medical device, consumer and health technology companies that are aiming to advance the development of new drugs, medical devices, precision diagnostics and health technologies, including applications in pediatrics.
“We are proud to welcome Virginia Tech to our historic Walter Reed campus – a campus that is shaping up to host some of the top minds, talent and innovation incubators in the world,” says Washington, D.C. Mayor Muriel Bowser. “The new Children’s National Research & Innovation Campus will exemplify why D.C. is the capital of inclusive innovation – because we are a city committed to building the public and private partnerships necessary to drive discoveries, create jobs, promote economic growth and keep D.C. at the forefront of innovation and change.”
Faculty from the Children’s National Research Institute and the Fralin Biomedical Research Institute at Virginia Tech Carilion (VTC) have worked together for more than a decade, already resulting in shared research grants, collaborative publications and shared intellectual property. Together, the two institutions will now expand their collaborations to develop new drugs, medical devices, software applications and other novel treatments for cancer, rare diseases and other disorders.
“Joining with Children’s National in the nation’s capital positions Virginia Tech to improve the health and well-being of infants and children around the world,” says Virginia Tech President Tim Sands, Ph.D. “This partnership resonates with our land-grant mission to solve big problems and create new opportunities in Virginia and D.C. through education, technology and research.”
The partnership with Children’s National adds to Virginia Tech’s growing footprint in the Washington D.C. region, which includes plans for a new graduate campus in Alexandria, Va. with a human-centered approach to technological innovation. Sands said the proximity of the two locations – just across the Potomac – will enable researchers to leverage resources, and will also create opportunities with the Virginia Tech campus in Blacksburg, Va. and the Virginia Tech Carilion Health Science and Technology campus in Roanoke, Va.
Carilion Clinic and Children’s National have an existing collaboration for provision of certain specialized pediatric clinical services. The more formalized partnership between Virginia Tech and Children’s National will drive the already strong Virginia Tech-Carilion Clinic partnership, particularly for children’s health initiatives and facilitate collaborations between all three institutions in the pediatric research and clinical service domains.
Children’s National and Virginia Tech will engage in joint faculty recruiting, joint intellectual property, joint training of students and fellows, and collaborative research projects and programs according to Michael Friedlander, Ph.D., Virginia Tech’s vice president for health sciences and technology, and executive director of the Fralin Biomedical Research Institute at VTC.
“The expansion and formalization of our partnership with Children’s National is extremely timely and vital for pediatric research innovation and for translating these innovations into practice to prevent, treat and ultimately cure nervous system cancer in children,” says Friedlander, who has collaborated with Children’s National leaders and researchers for more than 20 years. “Both Virginia Tech and Children’s National have similar values and cultures with a firm commitment to discovery and innovation in the service of society.”
“Brain and other nervous system cancers are among the most common cancers in children (alongside leukemia),” says Friedlander. “With our strength in neurobiology including adult brain cancer research in both humans and companion animals at Virginia Tech and the strength of Children’s National research in pediatric cancer, developmental neuroscience and intellectual disabilities, this is a perfect match.”
The design of the Children’s National Research & Innovation Campus not only makes it conducive for the hospital to strengthen its prestigious partnerships with Virginia Tech and Johnson & Johnson, it also fosters synergies with federal agencies like the Biomedical Advanced Research and Development Authority, which will collaborate with JLABS @ Washington, DC to establish a specialized innovation zone to develop responses to health security threats. As more partners sign on, this convergence of key public and private institutions will accelerate discoveries and bring them to market faster for the benefit of children and adults.
“The Children’s National Research & Innovation Campus pairs an inspirational mission to find new treatments for childhood illness and disease with the ideal environment for early stage companies. I am confident the campus will be a magnet for big ideas and will be an economic boost for Washington DC and the region,” says Jeff Zients, who was appointed chair of the Children’s National Board of Directors effective October 1, 2019. As a CEO and the former director of President Obama’s National Economic Council, Zients says that “When you bring together business, academia, health care and government in the right setting, you create a hotbed for innovation.”
Ranked 7th in National Institutes of Health research funding among pediatric hospitals, Children’s National continues to foster collaborations as it prepares to open its first 158,000-square-foot phase of its Research & Innovation Campus. These key partnerships will enable the hospital to fulfill its mission of keeping children top of mind for healthcare innovation and research while also contributing to Washington D.C.’s thriving innovation economy.
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PKD is a genetic disorder characterized by clusters of fluid-filled sacs (cysts) multiplying and interfering with the kidneys’ ability to filter waste from the blood.
When Lisa M. Guay-Woodford, M.D., McGehee Joyce Professor of Pediatrics at Children’s National Hospital, considers a brand-new gift, she likens it to 6 million gallons of “rocket fuel” that will power new research to better understand polycystic kidney disease.
Dr. Guay-Woodford received a $5.7 million dollar gift to support PKD clinical and research activities. PKD is a genetic disorder characterized by clusters of fluid-filled sacs (cysts) multiplying and interfering with the kidneys’ ability to filter waste from the blood. The kidneys’ smooth surface transforms to a bumpy texture as the essential organs grow oversized and riddled with cysts.
The extraordinary generosity got its start in an ordinary clinical visit.
Dr. Guay-Woodford saw a young patient in her clinic at Children’s National a few times in 2015. The child’s diagnosis sparked a voyage of discovery for the patient’s extended family and, ultimately, they attended a presentation she gave during a regional meeting about PKD. That led to a telephone conversation and in-person meeting as they invited her to describe “the white space” between what was being done at the time to better understand PKD and what could be done.
“It’s the power of the art and science of medicine. They come to see people like me because of the science. If we can convey to patients and families that who they are and their unique concerns are really important to researchers, that becomes a powerful connection,” she says. “The art plus the science equals hope. That is what these families are looking for: We give people the latest insights about their disease because information is power.”
The infusion of new funding will strengthen the global initiative’s four pillars:
Coordinated care for children and families impacted by renal cystic disease. The Inherited and Polycystic Kidney Disease (IPKD) program, launched September 2019, includes a cadre of experts working together as a team in the medical home so that “in a single, one-stop visit, Children’s National can address the myriad concerns they have,” she explains. A multi-disciplinary team that includes nephrologists, hepatologists and endocrinology experts meets weekly to ensure the Center of Excellence provides the highest-caliber patient care. The team includes genetic counselors to empower families with knowledge about genetic risks and testing opportunities. A nurse helps families navigate the maze of who to call about which issue. Psychologists help to ease anxiety. “There is stress. There is fear. There is pain that can be associated with this set of diseases. The good news is we can control their medical issues. The bad news is some children have difficulty coping. Our psychologists help children cope so they can be a child and do the normal things that children do,” she says.
Strengthening global databases to capture PKD variations. The team will expand its outreach to other centers located around the world – including Australia, Europe, India and Latin America – caring for patients with both the recessive and dominant forms of polycystic kidney disease, to better understand the variety of ways the disease can manifest in children. “We really don’t know a lot about kids with the dominant form of the disease. How hard should we push to control their blood pressure, knowing that could ease symptoms? What are the ramifications of experiencing acute pain compared with chronic pain? How much do these pain flareups interfere with daily life and a child’s sense of self,” she asks. Capturing the nuances of the worldwide experience offers the power of harnessing even more data. And ensuring that teams collect data in a consistent way means each group would have the potential to extract the most useful information from database queries.
Filling a ‘desperate need’ for biomarkers. Developing clinical trials for new therapies requires having biomarkers that indicate the disease course. Such biomarkers have been instrumental in personalizing care for patients with other chronic conditions. “We are in desperate need for such biomarkers, and this new funding will underwrite pilot studies to identify and validate these disease markers. The first bite at the apple will leverage our imaging data to identify promising biomarkers,” she says.
Genetic mechanisms that trigger kidney disease. About 500,000 people in the U.S. have PKD. In many cases, children inherit a genetic mutation but, often, their genetic mutation develops spontaneously. Dr. Guay-Woodford’s research about the mechanisms that make certain inherited renal disorders lethal, such as autosomal recessive polycystic kidney disease, is recognized around the world. The fourth pillar of the new project provides funding to continue her lab’s research efforts to improve the mechanistic understanding of what triggers PKD.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2019/11/polycystic-kidney-disease.png300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2019-11-14 17:30:452023-05-01 10:03:46$6M gift powers new PKD clinical and research activities
“We know that bariatric surgery improves markers of kidney health in severely obese adults and adolescents,” says Marva Moxey-Mims, M.D. “This research helps to elucidate possible differences in kidney disease outcomes between children and adults post-surgery.”
Adolescents with Type 2 diabetes experienced more hyperfiltration and earlier attenuation of their elevated urine albumin-to-creatinine ratio (UACR) after gastric bypass surgery compared with adults. This finding contrasts with adolescents or adults who did not have diabetes prior to surgery, according to research presented Nov. 8, 2019, during the American Society of Nephrology’s Kidney Week 2019, the world’s largest gathering of kidney researchers.
“Findings from this work support a recent policy statement by the American Academy of Pediatrics (AAP) that advocates for increasing severely obese youths’ access to bariatric surgery,” says Marva Moxey-Mims, M.D., Chief of the Division of Nephrology at Children’s National Hospital and a study co-author. “We know that bariatric surgery improves markers of kidney health in severely obese adults and adolescents. This research helps to elucidate possible differences in kidney disease outcomes between children and adults post-surgery.”
According to the AAP, the prevalence of severe obesity in youth aged 12 to 19 has nearly doubled since 1999. Now, 4.5 million U.S. children are affected by severe obesity, defined as having a body mass index ≥35 or ≥120% of the 95th percentile for age and sex.
In a Roux-en-Y gastric bypass, the surgeon staples the stomach to make it smaller, so people eat less. Then, they attach the lower part of the small intestine in a way that bypasses most of the stomach so the body takes in fewer calories.
The multi-institutional study team examined the health effects of such gastric bypass surgeries by comparing 161 adolescents with 396 adults enrolled in related studies. They compared their estimated glomerular filtration rates by serum creatinine and cystatin C. UACR was also compared at various time periods, up till five years after surgery.
Across the board, adolescents had higher UACR – a key marker for chronic kidney disease – than adults. However, for kids who had Type 2 diabetes prior to surgery, the prevalence of elevated UACR levels dip from 29% pre-surgery to 6% one year post-surgery. By contrast, adults who had diabetes prior to surgery and elevated UACR did not see a significant reduction in UACR until five years post-surgery.
While hyperfiltration prevalence was similar in study participants who did not have Type 2 diabetes, adolescents who had Type 2 diabetes prior to surgery had an increased prevalence of hyperfiltration for the duration of the study period.
Financial support for research described in this post was provided by the National Institute of Diabetes and Digestive and Kidney Diseases.
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ASN Kidney Week 2019 presentation
“Five-year kidney outcomes of bariatric surgery in adolescents compared with adults”
Friday, Nov. 8, 2019, 10 a.m. to noon (EST)
Petter Bjornstad, University of Colorado School of Medicine; Todd Jenkins, Edward Nehus and Mark Mitsnefes, all of Cincinnati Children’s Hospital; Marva M. Moxey-Mims, Children’s National Hospital; and Thomas H. Inge, Children’s Hospital Colorado.
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