Posts

little girl in hosptial corridor

A growing list of factors that impact CKD severity for kids

little girl in hosptial corridor

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments.

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease (CKD) for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments, according to an invited commentary published in the November 2018 edition of American Journal of Kidney Diseases.

Clinicians caring for “these vulnerable children should be mindful of these multiple competing and compounding issues as treatment options are being considered along the continuum from CKD to kidney failure to transplantation,” writes Marva Moxey-Mims, M.D., chief of the Division of Nephrology at Children’s National Health System.

The supplemental article was informed by lessons learned from The Chronic Kidney Disease in Children (CKiD) longitudinal study and conversations that occurred during the Frank M. Norfleet Forum for Advancement of Health, “African Americans and Kidney Disease in the 21st Century.”

African American children represent 23 percent of the overall population of kids with CKD in the CKiD study. While acquired kidney diseases can get their start during childhood when the diseases betray few symptoms, the full impact of illness may not be felt until adulthood. A number of factors can uniquely affect children of African descent, heightening risk for some kids who already are predisposed to suffering more severe symptoms. These include:

  • Preterm birth. African American children make up 36 percent of patients in CKiD with glomerular disease, which tends to have faster progression to end-stage renal disease. These diseases impair kidney function by weakening glomeruli, which impairs the kidneys’ ability to clean blood. Patients with a high-risk apolipoprotein L1 (APOL1) genotype already are at higher risk for focal segmental glomerulosclerosis (FSGS) and CKD. Researchers hypothesize that preterm birth may represent “a second hit that facilitates the development of glomerular damage resulting from the high-risk genotype.” According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, e.g., prior to 37 weeks gestation.
  • APOL1 genotype. Compared with children who had a low-risk genotype and FSGS, children with a high-risk genotype had higher rates of uncontrolled hypertension, left ventricular hypertrophy, elevated C-reactive protein levels and obesity.
  • Human immunodeficiency viral (HIV) status. About 65 percent of U.S. children with HIV-1/AIDS are African American. In a recent nested case-control study of children infected with HIV in the womb, infants with high-risk APOL1 genotypes were 3.5 times more likely to develop CKD with viral infection serving as “a likely second hit.”
  • Access to kidney transplant. African American adults experience a faster transition to end-stage renal disease and are less likely to receive kidney transplants. African American children with CKD from nonglomerular diseases begin renal replacement therapy 1.6 years earlier than children of other races, after adjusting for socioeconomic status. Their wait for dialysis therapy was 37.5 percent shorter. However, these African American children waited 53.7 percent longer for transplants. Although donor blood types, genetic characteristics and other biological factors each play contributing roles, “these findings may reflect sociocultural and institutional differences not captured by socioeconomic status,” Dr. Moxey-Mims writes.

To alleviate future health care disparities, she suggests that additional research explore the impact of expanding services to pregnant women to lower their chances of giving birth prematurely; early childhood interventions to help boost children’s educational outcomes, future job prospects and income levels; expanded studies about the impact of environmental toxicities on prenatal and postnatal development; and heightened surveillance of preterm infants as they grow older to spot signs of kidney disease earlier to slow or prevent disease progression.

“Clinicians can now begin to take into account genetics, socioeconomic status and the impact of the built environment, rather than blaming people and assuming that their behavior alone brought on kidney disease,” Dr. Moxey-Mims adds. “Smoking, not eating properly and not exercising can certainly make people vulnerable to disease. However, there are so many factors that go into developing a disease that patients cannot control: You don’t control to whom you’re born, where you live or available resources where you live. These research projects will be useful to help us really get to the bottom of which factors we can impact and which things can’t we prevent but can strive to mitigate.”

The article covered in this post is part of a supplement that arose from the Frank M. Norfleet Forum for Advancement of Health: African Americans and Kidney Disease in the 21st Century, held March 24, 2017, in Memphis, Tennessee. The Forum and the publication of this supplement were funded by the Frank M. Norfleet Forum for Advancement of Health, the Community Foundation of Greater Memphis and the University of Tennessee Health Science Center.

Marva Moxey Mims

Making the case for a comprehensive national registry for pediatric CKD

Marva Moxey Mims

“It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD.,” says Marva Moxey-Mims, M.D. “A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

Even though chronic kidney disease (CKD) is a global epidemic that imperils cardiovascular health, impairs quality of life and heightens mortality, very little is known about how CKD uniquely impacts children and how kids may be spared from its more devastating effects.

That makes a study published in the November 2018 issue of the American Journal of Kidney Diseases all the more notable because it represents the largest population-based study of CKD prevalence in a nationally representative cohort of adolescents aged 12 to 18, Sun-Young Ahn, M.D., and Marva Moxey-Mims, M.D., of Children’s National Health System, write in a companion editorial published online Oct. 18, 2018.

In their invited commentary, “Chronic kidney disease in children: the importance of a national epidemiological study,” Drs. Ahn and Moxey-Mims point out that pediatric CKD can contribute to growth failure, developmental and neurocognitive defects and impaired cardiovascular health.

“Children who require renal-replacement therapy suffer mortality rates that are 30 times higher than children who don’t have end-stage renal disease,” adds Dr. Moxey-Mims, chief of the Division of Nephrology at Children’s National. “It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD. A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

At its early stages, pediatric CKD usually has few symptoms, and clinicians around the world lack validated biomarkers to spot the disease early, before it may become irreversible.

While national mass urine screening programs in Japan, Taiwan and Korea have demonstrated success in early detection of CKD, which enabled successful interventions, such an approach is not cost-effective for the U.S., Drs. Ahn and Moxey-Mims write.

According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, prior to 37 weeks gestation. Because of that trend, the commentators advocate for “a concerted national effort” to track preterm and low birth weight newborns. (These infants are presumed to have lower nephron endowment, which increases their risk for developing end-stage kidney disease.)

“We need a comprehensive, national registry just for pediatric CKD, a database that represents the entire U.S. population that we could query to glean new insights about what improves kids’ lifespan and quality of life. With a large database of anonymized pediatric patient records we could, for example, assess the effectiveness of specific therapeutic interventions, such as angiotensin-converting enzyme inhibitors, in improving care and slowing CKD progression in kids,” Dr. Moxey-Mims adds.

Making the grade: Children’s National is nation’s Top 5 children’s hospital

Children’s National rose in rankings to become the nation’s Top 5 children’s hospital according to the 2018-19 Best Children’s Hospitals Honor Roll released June 26, 2018, by U.S. News & World Report. Additionally, for the second straight year, Children’s Neonatology division led by Billie Lou Short, M.D., ranked No. 1 among 50 neonatal intensive care units ranked across the nation.

Children’s National also ranked in the Top 10 in six additional services:

For the eighth year running, Children’s National ranked in all 10 specialty services, which underscores its unwavering commitment to excellence, continuous quality improvement and unmatched pediatric expertise throughout the organization.

“It’s a distinct honor for Children’s physicians, nurses and employees to be recognized as the nation’s Top 5 pediatric hospital. Children’s National provides the nation’s best care for kids and our dedicated physicians, neonatologists, surgeons, neuroscientists and other specialists, nurses and other clinical support teams are the reason why,” says Kurt Newman, M.D., Children’s President and CEO. “All of the Children’s staff is committed to ensuring that our kids and families enjoy the very best health outcomes today and for the rest of their lives.”

The excellence of Children’s care is made possible by our research insights and clinical innovations. In addition to being named to the U.S. News Honor Roll, a distinction awarded to just 10 children’s centers around the nation, Children’s National is a two-time Magnet® designated hospital for excellence in nursing and is a Leapfrog Group Top Hospital. Children’s ranks seventh among pediatric hospitals in funding from the National Institutes of Health, with a combined $40 million in direct and indirect funding, and transfers the latest research insights from the bench to patients’ bedsides.

“The 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver exceptional care across a range of specialties and deserve to be highlighted,” says Ben Harder, chief of health analysis at U.S. News. “Day after day, these hospitals provide state-of-the-art medical expertise to children with complex conditions. Their U.S. News’ rankings reflect their commitment to providing high-quality care.”

The 12th annual rankings recognize the top 50 pediatric facilities across the U.S. in 10 pediatric specialties: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology. Hospitals received points for being ranked in a specialty, and higher-ranking hospitals receive more points. The Best Children’s Hospitals Honor Roll recognizes the 10 hospitals that received the most points overall.

This year’s rankings will be published in the U.S. News & World Report’s “Best Hospitals 2019” guidebook, available for purchase in late September.

child in wheelchair with mom

Potential to replace race as a risk factor for kidney-transplant failure

child in wheelchair with mom

Right now, more than 100,000 adult and pediatric patients in the U.S. are waiting for a life-saving kidney donation. Thirteen of them die each day while awaiting a transplant. However, a significant portion of kidneys from deceased donors are discarded because they literally don’t make the grade – a scoring system known as the kidney donor profile index (KDPI) that aims to predict how long a donor kidney will last in an intended recipient based on a variety of factors, including the donor’s age, size and health history.

Ethnicity and race are also part of that scoring system, explains Marva Moxey-Mims, M.D., FASN, chief of the Division of Nephrology at Children’s National Health System. That’s partly because research over the years has suggested that kidneys from certain racial groups, including African-Americans, may not have the same longevity as those from other groups.

But race might not be the right marker to consider, Dr. Moxey-Mims counters. More recent studies have shown that a particular gene known as APOL1 might better predict risk of kidney-transplant failure. APOL1 high-risk variants are associated with a wide range of kidney diseases, with retrospective studies suggesting that they could be a key cause of failure in some donated kidneys. Although this gene is found almost exclusively in people of recent African descent, only about 13 percent of that population has high-risk APOL1 variants that might cause kidney problems.

“Instead of putting all African-American donor kidneys in one proverbial ‘bucket,’ we might be able to use this gene to determine if they truly carry a higher risk of early failure,” Dr. Moxey-Mims says.

To more definitively confirm whether this gene could be used as a proxy for heightened kidney-failure risk, Dr. Moxey-Mims and colleagues across the country are participating in the APOL1 Long-Term Kidney Transplantation Outcomes Network (APOLLO) study, she and Dr. Barry Freedman explain in a perspective published online April 27, 2018, in Clinical Journal of the American Society of Nephrology. The APOLLO study will tap people accessing the hundreds of transplant centers scattered across the nation, prospectively genotyping deceased and living African-American kidney donors as well as kidney-transplant recipients to assess whether they carry high-risk APOL1 gene variants. Living donors and transplant recipients will be followed for years to gauge how their kidneys fare over time.

The researchers, Dr. Moxey-Mims explains, hope to answer whether the APOL1 high-risk gene variants in donor kidneys could replace race as a risk factor when calculating the KDPI score and whether recipients’ own APOL1 gene variants impact transplant failure risk. They also hope to better understand the risk to living donors. “If a living donor has an increased risk of kidney failure,” she adds, “he or she can make a more educated decision about whether to donate a kidney.”

Dr. Moxey-Mims plays a pivotal role as the chair of the study’s steering committee, a group made up of the study’s principal investigators at all 13 clinical sites and the Data Coordinating Center, as well as the program officials from the National Institutes of Health funding institutes (National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, and National Institute on Minority Health and Health Disparities). She will play a key part in helping to ensure that the study stays on track with recruitment goals, as well as publicizing the study at national meetings.

The study also includes a Community Advisory Council, a group made up of stakeholders in this study: 26 African-Americans who either have donated a kidney, received a kidney donation, are on dialysis awaiting a kidney transplant, or have a close relative in one of those categories. This group has helped to steer the study design in multiple ways, Dr. Moxey-Mims explains. For example, they have worked with study leaders to simplify the language on consent forms, helped to delineate which data study participants might want to receive when the study is completed, and helped to publicize the study in their communities by giving talks at churches and other venues.

Eventually, Dr. Moxey-Mims says APOLLO study researchers hope that clarifying the role of the APOL1 gene in kidney-transplant failure could lead to fewer discarded kidneys, which could boost the number of available kidneys for patients awaiting transplants.

“Down the road, the pool of patients awaiting transplant might have access to more kidneys because available organs aren’t getting a bad score simply because the donor is African-American,” she says. “We hope this might shorten the wait for some patients and their families who are desperate to get that call that a kidney is finally available.”

Financial support for research reported in the post was provided by the National Institutes of Health under grant numbers R01 DK084149, R01 DK070941 and U01 DK116041.

Enhancing pediatric nephrology clinical trial development

Fewer than 50 percent of pharmaceuticals approved by federal authorities are explicitly approved for use in kids, and even fewer devices are labeled for pediatric use.

When children develop kidney disease, it can play out in dramatically different ways. They can experience relatively mild disorders that respond to existing treatments and only impact their lives for the short term. Children also can develop chronic kidney disease that defies current treatments and can imperil or end their lives.

Fewer than 50 percent of pharmaceuticals approved by federal authorities are explicitly approved for use in kids, and even fewer devices are labeled for pediatric use. Congress has offered incentives to manufacturers who study their treatments in children, but the laws do not require drug makers to demonstrate statistical significance or for the clinical trial to improve or extend children’s lives.

To overcome such daunting obstacles, the American Society of Pediatric Nephrology established a Therapeutics Development Committee to forge more effective public-private partnerships and to outline strategies to design and carry out pediatric nephrology clinical trials more expeditiously and effectively.

“We have seen how other pediatric subspecialties, such as cancer and arthritis, have leveraged similar consortia to address mutual concerns and to facilitate development of new therapeutics specific to those diseases,” says Marva Moxey-Mims, M.D., chief of the Division of Nephrology at Children’s National Health System and a founding committee member. “As a group, we aim to collectively identify and remedy the most pressing needs in pediatric nephrology. As just one example, the committee could help to increase the number of sites that host research studies, could expand the pool of potential study volunteers and could lower the chances of duplicating efforts.”

A paper summarizing their efforts thus far, “Enhancing clinical trial development for pediatric kidney diseases,” written by Dr. Moxey-Mims and 15 co-authors, was published online Aug. 30 by Pediatric Research. The journal’s editors will feature the review article in the “Editor’s Focus” of an upcoming print edition of the publication.

The committee is comprised of academic pediatric nephrologists, patient advocates, private pharmaceutical company representatives and public employees at the Food and Drug Administration and the National Institutes of Health. But it is likely to grow in size and in stakeholder diversity.

Already, committee members have learned that they achieve better results by working together. Early communication can avoid flaws in designing clinical trials, such as overestimating the volume of clinical samples that can feasibly be collected from a small child, or that could misinterpret the type of data needed to secure federal approval.

While public and private investigators took similar approaches to clinical trial design, academic investigators were more conceptual as they summarized their study design Road Map. Industry representatives, by contrast, included more granular detail about study organization and milestones along the path toward regulatory approval.

According to the study authors, both groups understand the critical role that patients and families can play in early research study design, such as accelerating patient recruitment, bolstering the credibility of research and helping to translate research results into actual clinical practice.

“We are pleased to have created a forum that allows participants to share valuable viewpoints and concerns and to understand how regulations and laws could be changed to facilitate development of effective medicines for children with kidney disease,” says Dr. Moxey-Mims. “We hope the relationships and trust forged through these conversations help to speed the development and approval of the next generation of therapies for pediatric renal disease.”

A close-up of Dr. Marva Moxey Mims at Children's National.

Children’s National welcomes Marva Moxey-Mims, M.D., renowned nephrologist, as incoming Division Chief

A close-up of Dr. Marva Moxey Mims at Children's National.

Marva Moxey-Mims, M.D., a leading expert in chronic kidney disease and glomerular disease who has conceptualized and overseen multicenter clinical studies aimed at improving chronic kidney disease treatment, has been named Chief of Pediatric Nephrology at Children’s National Health System.

Dr. Moxey-Mims comes to Children’s National from the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health where she served as Deputy Director for clinical science and oversaw a research portfolio that included clinical trials for kidney disease and genitourinary dysfunction in adults and children. As Pediatric Nephrology Division Chief, Dr. Moxey-Mims plans to add new staff and restructure a division already ranked among the nation’s leaders by U.S. News & World Report in order to carve out dedicated time for research and improve care for children with kidney disease.

”Children’s National is honored to welcome Dr. Moxey-Mims as the new leader for our talented nephrology team,” says Robin Steinhorn, M.D., senior vice president of the Center for Hospital-Based Specialties. “She brings unparalleled expertise in this field, is a member of a number of influential national committees and has authored more than 90 scientific publications, including peer-reviewed articles and book chapters. Under her guidance, Pediatric Nephrology at Children’s is well-positioned to continue to lead the nation in clinical care and research.”

“I want to inspire the division,” Dr. Moxey-Mims says. “I want the faculty to be happy in their work here and to look forward to coming to work every day. I want them to have enough time to pursue their academic interests, so clinicians not only continue to provide excellent patient care but also can conduct research. All of the staff has potential projects in mind; it’s just a matter of finding the time to do them.”

From a pragmatic standpoint, Children’s pediatric nephrologists will start with what is feasible: Continuing and expanding current cross-disciplinary research projects.

“There are some research projects that will be important to pursue, but we just don’t have the building blocks in place right now to move in that specific direction,” Dr. Moxey-Mims says. “However, continuing ongoing collaborations with our colleagues in neonatologyoncologyhematology and urology are reasonable places to start. I agree with the cliché that success breeds success. If we have an established collaboration and can build on it, that is how we start expanding our research enterprise.”

To that end, the division is in the early stage of joining an existing consortium that is studying four types of glomerular disease, conditions caused by varying mechanisms that often lead to kidney failure. “Information that is gathered will inform care going forward,” she says. “Part of what is being done in these studies is obtaining a better understanding of how disease progresses in different groups of children and adults and quantifying the impact of varying treatment approaches. It’s very exciting for Children’s National to be a new player in this.”

Dr. Moxey-Mims received her undergraduate degree from McGill University in Montreal and her medical degree from Howard University in Washington, D.C. She completed her pediatric residency and clinical pediatric nephrology training at Children’s National and from 1994 to 1999 worked at Children’s National as a staff nephrologist.

“Returning to Children’s has been a wonderful homecoming,” Dr. Moxey-Mims says. “I wanted to return to the hospital setting and have direct exposure to patients. I missed that. In this new role, I can participate in patient care, as well as foster an environment that spurs even more research. It’s really the best of both worlds.”