Up to 70 percent of adults with sickle cell anemia will develop chronic kidney disease, many of whom will require dialysis or transplantation. But since the damage often begins in childhood, identifying the early signs of kidney disease could shift that trajectory.
That’s the goal of Jeffery Lebensburger, D.O.’s research at Children’s of Alabama, for which he was recently awarded a prestigious National Institutes of Health R01 grant. Julie Kanter, M.D., who co-directs the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham (UAB), is also involved.
“This project will develop a novel approach to monitoring changes in kidney function over time that is specific for patients with sickle cell anemia,” said Lebensburger, who directs UAB’s hematology section in the Division of Pediatric Hematology. “This will improve our clinical capacity to identify sickle cell anemia patients who are at risk for chronic kidney disease and who may benefit from additional prospective therapies.”
The early signs of kidney disease are usually silent. By the time obvious markers like protein in the urine develop, the loss of kidney function is often too advanced to reverse. “We need to control it in childhood,” Lebensburger said. Particularly since people with sickle cell anemia who go on dialysis are eight times more likely to die from kidney-related complications within seven years than those without the disease.
“Given the high mortality early in life from kidney disease, it is vital that we monitor kidney disease progression in children and adults,” he said. But the standard glomerular filtration rate (GFR) blood test provides, at best, a “guess” of kidney function. The tests also weren’t developed for sickle cell patients, he said. The gold standard, a measured test of how well the kidney eliminates a contrast agent, takes four to six hours and is very expensive.
“For us to appropriately track kidney function in this population and prevent the devastating complications of renal disease in our patients, we need a GFR equation that is validated for those with sickle cell, not for other populations,” Lebensburger said. Which is what his research is designed to do.
“We’re starting from scratch to develop this,” he said, performing normal blood work in 200 children and 200 adults and then developing a new calculation of kidney function that is valid for our sickle cell patients. “Then we’ll know what’s happening and can better track patients’ kidney function and prevent the devastating effects of kidney disease.”
Children’s of Alabama provides more days of dialysis to babies than any institution in the world. Indeed, Children’s nephrologists and intensivists pioneered the use of dialysis in newborns and young children by retrofitting a machine used for adult heart failure patients. Now, with U.S. Food and Drug Administration-approved dialysis machines for young children on the market, the team has been inundated with requests from other hospitals for training and information.
The result is the Neonatal and Infant Course for Kidney Support (NICKS), a one-and-a-half day educational program that combines didactic teaching from a variety of specialists, an opportunity to have a parental perspective, “hands-on” skills sessions and virtual small group case simulations.
“As medicine advances and we continue to create innovative answers to problems, it is imperative that we offer up what we have learned in a practical, ‘hands-on’ way,” said course co-founder and acute dialysis nurse practitioner Kara Short, MSN, CRNP.
“There’s a huge need across the country and across the world for people to understand how dialysis is different for newborns and small kids,” said course co-founder David Askenazi, M.D., MsPH, FASN, who directs the Pediatric and Infant Center for Acute Nephrology (PICAN) at Children’s. “We cover the whole gamut of how to build a program with the hope that we can educate them, inspire them and provide them with tools so they can go back to their institutions and succeed in caring for small kids.”
While the course was originally designed to be held in person, COVID-19 forced it online. That hasn’t hurt its popularity. The first course, held in July, sold out in a few days and by early September there was a 20-person waiting list for the October program. Participants have come from throughout the world, including Israel, Qatar, and Canada. The interest has been so great that Short and Askenazi doubled the number of participants from 20 to 40.
“The feedback has been tremendous,” said Short. Among the comments she’s received from participants:
“I loved this! I was very impressed with the overall quality. Well done, I really enjoyed it!”
“The conference was extremely well run, efficient and very informative. I know I learned a lot.”
“Excellent job on your inaugural course. Would highly recommend.”
“Enjoyed attending with lots of good information. Looking forward to reviewing policies to help grow our own program.”
Pediatric nephrologistErica Christen Bjornstad, M.D., Ph.D., MPH,has been working inglobal health since college. As a Peace Corps volunteer she served as a rural public health volunteer in Ecuador, and in the years after brought her public health expertise to Peru, Afghanistan, Malawi, and Tanzania. In fact, it was her work with trauma surgeons in Malawi, one of the five poorest countries in the world, during her fellowship at the University of North Carolina-Chapel Hill that stoked her interest in acute kidney injury (AKI).
The condition is a significant cause of morbidity and mortality in the post-surgical and ICU setting and is typically diagnosed late in the disease state when severe kidney damage may have already occurred. In poor countries like Malawi, which don’t have the infrastructure required to obtain and run laboratory blood tests, the diagnosis may never come. Patients then develop end-stage renal failure but have little, if any, access to dialysis.
During her fellowship, Bjornstad brought a point-of-care urine dipstick test to Malawi to provide instant results on kidney function. Now at Children’s of Alabama, she hopes to bring that test – and her deep knowledge of the unmet nephrology needs in developing countries— to Zambia through the hospital’s existing relationship with the Centre for Infectious Disease Research in Zambia (CIDRZ). “Zambia is better off than Malawi,” she said, “but still struggles with a lot of scarcities and lab shortages.” COVID-19 has exacerbated those problems exponentially, she said. “Having a point-of-care test would be quite valuable.”
Such partnerships are what enticed her to Children’s in 2019 when she finished her fellowship. It was important, she said, that the pediatrics department at the University of Alabama Birmingham (UAB) wants to build its global health presence in a sustainable way, “not popping in and popping out.”
That means providing the education and support to work alongside a developing country improving its own medical infrastructure. The people who live in the country “are 100 times more prepared to ask the right questions and provide potential solutions that we never would have thought of,” she said, “because they are there and they know what works and what doesn’t.”
The relationships we build with these institutions, if done right, can lead to great changes in both,” she said. “But we have to be careful that it is done in a thoughtful way and that the U.S. side is not doing all the benefitting.” The CIDRZ/UAB partnership, she said, exemplifies sustainability.
But there needs to be more focus on kidney disease. “The need for nephrology is underappreciated and often overlooked in global health until there is a very dire medical emergency,” she said. So finding ways to bring the specialty to areas with few resources – as with a dipstick – is critical. “I can’t take a lab machine on the plane with me,” she said. “But if I can throw some dipsticks in my pack and diagnose AKI, that could be revolutionary.”
When it comes to kids on dialysis, food really is medicine. “We can provide state-of-the-art dialysis treatment and medications, but if they don’t follow a strict diet, they don’t do well,” said Children’s of Alabama Dialysis Director Sahar Fathallah-Shaykh, M.D. That includes a higher risk of hospital admission, infections and even mortality. Plus, it may make them ineligible for transplant because of poor healing, increased risk of infection and poor outcome.
The strict diets are very low in potassium, salt and phosphorus, with no processed or fast food. “This leaves a majority of our patients with a very difficult-to-obtain diet,” she said, particularly since half have significant food insecurity. “If we can’t meet the basic need of food, we’re not helping them that much.”
Which is why she and her team developed the Food as Medicine program in the spring of 2020. Families who qualify based on income and expenses receive a monthly box of non-perishable supplies for their child, as well as support from a renal dietician in how to use them.
“When we started we were hoping to provide them with fresh ingredients once a week, but then COVID came,” Fathallah-Shaykh said, restricting the ability of families to pick up the food on a weekly basis.
Packages include almond milk, rice, pasta, butter, animal crackers, dried herbs and seasonings, grains, cereals, oils for cooking, canned fruits and unsalted vegetables, canned tuna and chicken, and even snacks such as unsalted pretzels and Rice Krisipies Treats. Once the pandemic ends, “we hope that fresh vegetables will join the mix,” Fathallah-Shaykh said.
The unit typically has about 25 patients on dialysis and about half qualify for the program. They claim their boxes when they come for treatment.
The program has been funded, in part, by the Children’s Table fundraiser, a food event and fundraiser to raise awareness about the importance of dietary choices in the health of children and management of pediatric disease. In past years, participants enjoyed tasting plates, signature cocktails, beer, wine and dessert from some of the top chefs in the state. The event has raised more than $100,000 over the past three years to support families’ nutritional needs.
Now the team is trying to figure out how to keep the program going given the COVID-19 pandemic and the challenge it presents for in-person events.
“Without that funding,” Fathallah-Shaykh said, “these children may die if we don’t help them with their basic dietary needs. It’s really that serious.”
Ventricular assist devices (VAD), which help patients bridge the gap between late-stage heart failure and transplant or buy patients time while their hearts heal from trauma or infection, have been available for adults since the 1990s. But with no pediatric devices, Children’s of Alabama pediatric cardiologistF. Bennett Pearce, M.D., who, at the time, worked under the umbrella of the the adult transplant program at the University of Alabama-Birmingham (UAB), tried to adapt adult VAD devices for adolescents and children as young as 12.
But the devices and hardware required to attach them to the failing heart were often too large to fit within a child’s smaller thoracic volume, and the blood capacity was so high the devices had to operate at a very low heart rate, increasing the risk of thrombosis.
That all changed when Pearce read an article about a new pediatric VAD, the Berlin Heart EXCOR, that was just entering clinical studies. He was on vacation at the time and when he returned immediately worked with the UAB team to ensure the university could join the trials.
Their first patient received the Berlin VAD in 2005, making UAB one of the first hospitals in the southeast to perform the surgery. A second child received it a year later. Both were highly successful, Pearce said. One child later received a transplant and the other recovered from myocarditis.
The results of that trial led to the device’s U.S. Food and Drug Administration approval in 2011, and in 2012 investigators from UAB were among the authors of a landmark paper published in The New England Journal of Medicine reporting the results of the trial.
Since then, other devices have entered the market, and the pediatric ventricular support transplant advanced heart failure program moved to Children’s of Alabama where it has flourished. “We have a very experienced team on the pediatric cardiology heart failure side with experienced transplant coordinators, excellent surgeons, outstanding CVICU staff, and strong clinical research interests in pediatric circulatory support,” Pearce said. “That’s why it works so well today.”
Since 2001, 39 children, ranging from newborns to teenagers, most of whom are bridging to transplant, have received VADs; 27 since the program moved to Children’s. The success rates have improved over time, Pearce said, reflecting improvments in device technology, anticoagulation treatment and accumulated experience. “All patients supported in 2020 have had either successful bridge to transplant or recovery,” he said.
The children remain on the devices for weeks, months, “even close to a year,” Pearce said, often in the hospital. Even those who are discharged, however, require a high level of clinical support. Since many live hours away from Children’s, the team trains local clinicians, family and caregivers in the specialized support these patients need
The greatest advantage of our program, he said, “is that this kind of work, although intense, has the potential for tremendous satisfaction because of the often miraculous outcomes.”
It is the most complex cardiothoracic surgery performed in newborns, one in which surgeons literally construct a new, larger aorta for babies born with hypoplastic left heart syndrome (HLHS). Called the Norwood procedure, it must be done within the infant’s first week of life, followed by a second surgery when the baby is 3 to 6 months, and a third at age 4 or 5.
In the past five years, surgeons at Children’s of Alabama have completed 54 Norwoods. Just three babies died, for a mortality rate of 5.5 percent. That compares to a national average of about 15 percent, based on statistics from the Society of Thoracic Surgeons Congenital Heart Surgery Database, which tracks all congenital heart surgeries in the country. In addition, the one-year survival rate at Children’s is about 90 percent compared to the landmark Single Ventricle Reconstruction trial, which had a one-year mortality rate of about 70 percent.
“We are obviously really proud of where we are,” said Robert Dabal, M.D., chief of pediatric cardiothoracic surgery at Children’s.“It’s a combination of better resources and the evolution of a well-developed team.”
The cardiothoracic program truly took off in 2012, when the Benjamin Russell Hospital for Children opened and the program moved over from the University of Alabama at Birmingham (UAB). Before that, Dabal said, there were just seven pediatric cardiovascular intensive care unit (CVICU) beds; two dedicated pediatric cardiacintensivists; and nurses who took care of both adult and pediatric patients. Just one surgeon performed Norwood procedures.
Today, the Bruno Pediatric Heart Center, which occupies most of the fourth floor of the hospital, boasts a 20-bed CVICU with three surgeons performing Norwood procedures, seven dedicated intensivists and a large pool of nurses who only take care of children.
“We are much better in all phases of care,” Dabal said, including preoperative diagnosis. In the past, only about half of infants born with the condition were diagnosed in utero; today that figure is closer 80 percent. “It’s a testament to the hard work of the obstetricians and pediatric cardiologists who are making the diagnosis,” he said. The earlier notice enables surgeons to better plan for the surgery, ensures the mother delivers at UAB where the newborn can receive immediate care and helps the family begin to process and understand a life-changing diagnosis.
The team continually looks for opportunities to improve outcomes and isn’t afraid of change. For instance, Dabal said, they are now more aggressive about avoiding ventilation and try to get the babies to eat by mouth. They also encourage patient bonding with parents during the first few days after birth, “which we think is very important for later development.”
In addition, everything, from pre-operative to operative to postoperative care has become more standardized, leaving less room for error. While there are numerous techniques for the Norwood procedure, Dabal said, “we’ve tried to standardize our approach better so that all our babies get a very similar operation.”
Another contributing factor to the outstanding one-year survival is a home-based interstage monitoring program Children’s instituted. The hospital was an early national adopter of this program, in which parents use an iPad and special app to closely monitor their baby’s condition and keep nurses notified of any changes. The use of technology allows for much closer follow-up from a distance while still maintaining the same high levels of in-person care in the pediatric cardiology clinic.
But all the statistics in the world can’t make up for the most important improvement the Children’s program has seen, Dabal said, which is improved long-term survival with a good quality of life, the “ultimate goal” with congenital heart disease. “Success in congenital heart surgery can’t be measured in postoperative or one-year outcomes,” he said. “We strive to allow these babies to grow up and live the best lives that they can.”
Jessica Schmitt, M.D., Assistant Professor in Pediatric Endocrinology and Diabetes, earned her medical degree from the University of Alabama at Birmingham. Dr. Schmitt completed her pediatric residency at Cincinnati Children’s Hospital in Cincinnati, Ohio. She started her pediatric endocrinology and diabetes fellowship at Massachusetts General Hospital in Boston and completed her fellowship at the University of Alabama at Birmingham. Her clinical and research interests include quality improvement, specifically assessing process changes to improve management of and outcomes for youth with diabetes.
Nora Switchenko, M.D., Assistant Professor in Neonatology, earned her medical degree at Oregon Health and Science University in Portland, Ore. Dr. Switchenko completed her pediatric residency and her neonatology fellowship at the University of Utah in Salt Lake City, Utah. Her clinical and research interests include improving care for sick neonates in resource limited areas of the world with a particular focus on respiratory support for small and premature infants.
Carmelle Wallace, M.D., MPH, DTMH, Assistant Professor in Pediatric Emergency Medicine, earned her medical degree from Baylor College of Medicine in Houston, Texas. Dr. Wallace completed her pediatric residency at the University of Texas-Southwestern in Dallas, Texas and completed her pediatric emergency medicine fellowship and global health fellowship at Children’s Hospital of Philadelphia in Philadelphia, Pa. Her clinical and research interests include international pediatric emergency medicine capacity building, child human rights and international and domestic child trafficking and abuse. She has worked in Zambia, Tanzania, Swaziland, South Africa, India and Laos.
Guillermo Beltran Ale, M.D., Assistant Professor in Pediatric Pulmonary and Sleep Medicine, earned his medical degree at Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado in Lima, Peru. Dr. Beltran Ale completed his pediatric residency and pediatric pulmonology fellowship at Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio. His major research interests include Pulmonary Alveolar Proteinosis with a focus on BAL based diagnosis and optimizing care for pulmonary patients who are technology dependent with a focus on infections diagnosis and treatment. His clinical interests are aerodigestive pathology, the integrative care of patients on long term ventilation and technology dependence, rare lung diseases and pulmonary transplantation.
Vidit Bhargava, M.D., Assistant Professor in Pediatric Critical Care, earned his medical degree at Byramjee Jeejeebhoy Medical College in Pune, India. Dr. Bhargava completed his pediatric residency at the University of Texas Medical Branch in Galveston, Texas. He did a pediatric critical care fellowship and emergency ultrasound fellowship at Stanford University in Palo Alto, Calif.
Jared Buchan, M.D., Instructor in Pediatric Emergency Medicine, earned his medical degree from Florida State University in Tallahassee, Fla. Dr. Buchan completed his pediatric residency at Memorial Health University Medical Center in Savannah, Ga.
Viral Jain, M.D., Assistant Professor in Neonatology, earned his medical degree from MGM Medical College, Mumbai, India. Dr. Jain completed his pediatric residency at Case Western Reserve University in Cleveland, Ohio. He did his neonatology fellowship and research fellowship at Cincinnati Children’s Hospital in Cincinnati, Ohio. His primary area of interest is in Developmental Origins of Health & Disorders (DOHaD) or how changes during early period of in utero development influences life-long outcomes, and neonatal evidence-based medicine. He is also interested in exploring family’s contribution to young child’s learning and is the founder of TinyVoices – a patient advocacy program through which is founded the nationally renowned NICU Bookworms, a NICU Infant Reading program. Dr. Jain is also a children’s storybook writer and a musician and has written storybooks for NICU infants as well as written songs with Grammy award winners for NICU families.
Jeremy Loberger, M.D., Assistant Professor in Pediatric Critical Care Medicine, earned his medical degree at the University of South Carolina in Colombia, S.C. Dr. Loberger completed his combined internal medicine and pediatric residency at the University of South Carolina in Greenville, S.C. He did a pediatric critical care fellowship at the University of Alabama at Birmingham. His major research/clinical interests include quality improvement and clinical research on the topics of extubation readiness assessment, mechanical ventilation and sepsis.
Brittany Marlin, M.D., Instructor in Pediatric Hospital Medicine, earned her medical degree at the Florida State University in Tallahassee, Fla. Dr. Marlin completed her pediatric residency at the University of Alabama at Birmingham.
Pedro Anis Nourani, M.D., Assistant Professor in Pediatric Pulmonary and Sleep Medicine, earned his medical degree at the University of São Paulo in Ribeirão Preto, Brazil and completed his pediatric residency at Texas A&M’s Driscoll Children’s Hospital in Corpus Christi, Texas. Dr. Nourani completed his sleep medicine and pediatric pulmonology fellowships at the University of Alabama at Birmingham. His clinical activity has an emphasis on pediatric sleep disorders, Continuous Positive Airway Pressure (CPAP) therapy and general pediatric pulmonology disorders. His clinical research focuses on the identification of different sleep parameters related to clinical outcomes of sickle cell disease as potential targets for intervention.
Bhuvana Sunil, M.D., Assistant Professor in Pediatric Endocrinology and Diabetes, earned her medical degree from the Bangalore Medical College & Research Institute in Bengaluru, India. Dr. Sunil completed her pediatric residency at the Harlem Hospital Center in New York, N.Y. She completed her pediatric endocrinology and diabetes fellowship at the University of Alabama at Birmingham. Her clinical and research interests include obesity, type 2 diabetes, dyslipidemia and metabolic syndrome.
Kent Willis, M.D., Assistant Professor in Neonatology, earned his medical degree at the Ben-Gurion University of the Negev in Beer Sheva, Israel. Dr. Willis completed his pediatric residency at the Our Lady of the Lake Children’s Hospital in Baton Rouge, La., and his neonatology fellowship at the University of Tennessee Health Science Center in Memphis, Tenn. His research interests include understanding how commensal fungi, the mycobiome, influence newborn physiology and disease, principally via exploring the gut-lung axis in bronchopulmonary dysplasia. Willis Lung Lab is supported by the NIH, NHLBI K08HL151907, the UAB Microbiome Center and UAB Pediatrics.
Cynthia Wozow, D.O., Assistant Professor in Pediatric Rehabilitation Medicine, earned her medical from William Carey College of Osteopathic Medicine in Hattiesburg, Miss. Dr. Wozow completed her physical medicine and rehabilitation residency at the University of Texas-San Antonio in San Antonio, Texas and completed her pediatric physical medicine and rehabilitation medicine fellowship at Baylor College of Medicine and Texas Children’s Hospital in Houston, Texas. Her clinical interests include cerebral palsy, spasticity management, congenital neuromuscular disorders, brachial plexus injuries, transitional care, electrodiagnostic medicine and medical education.
Leslie Collins, M.D., Assistant Professor in Pediatric Cardiology, earned her medical degree at the East Carolina University – Brody School of Medicine. Dr. Collins completed her pediatric residency and pediatric cardiology fellowship at the University of Alabama at Birmingham. Her research/clinical interests include imaging, fetal ECHO, and heart failure and transplant.
Austin Kane, M.D.,AssistantProfessor in Pediatric Cardiology, earned his medical degree at Columbia University College of Physicians and Surgeons in New York, New York. Dr. Kane completed his pediatric residency at Northwestern University Feinberg School of Medicine in Chicago, Illinois. He completed a fellowship in pediatric cardiology at Emory University School of Medicine in Atlanta, Georgia and an additional fellowship in pediatric and congenital electrophysiology. Prior to joining the University of Alabama at Birmingham, he was a pediatric and congenital electrophysiology attending at Providence Sacred Heart Medical Center and Children’s Hospital in Spokane, Washington.
Khalisa Syeda, D.O., AssistantProfessor in Pediatric Cardiology, earned her medical degree at the University of North Texas in Fort Worth, Texas. Dr. Syeda completed her pediatric residency at the University of Illinois at Chicago and her pediatric cardiology fellowship at the University of Texas Health Science Center in Houston, Texas. Her research/clinical interests include pediatric cardiology, imaging, fetal echocardiography and preventive cardiology.
Through a generous donation by Robert and Kathleen Israel, Children’s of Alabama is now home to new technology that helps dramatically prevent brain injury and improve brain development and function in its sickest patients.
Children’s of Alabama is thrilled to announce a very generous gift of a cutting-edge technology designed to help reduce the risk of brain injury in preterm infants. The gift was donated by Robert and Kathleen Israel in honor of the care their daughter, Ivy, received in the Neonatal Intensive Care Unit (NICU) in 2018. Ivy is home and doing very well. “The NICU team at Children’s of Alabama saved our daughter’s life,” said Robert Israel, “and we are forever grateful.”
“This new technology made possible by the Israel family is helping us dramatically prevent brain injury and improve brain development and function in our sickest patients,” said Manimaran Ramani, M.D., director of the NeuroNICU program.
Preterm infants born at 30 weeks or earlier are at higher risk for developing intraventricular hemorrhage (IVH), which is associated with long-term neurocognitive and motor deficits. The risk for neurocognitive and motor deficits is also higher for term infants with hypoxic-ischemic encephalopathy (HIE), seizures, metabolic disorders, or stroke, and those undergoing ECMO therapy.
However, a multidisciplinary initiative in the NICU at Children’s of Alabama and the University of Alabama at Birmingham (UAB) called NeuroNICU B.R.A.I.N. (Brain Rescue and Avoidance of Injury in Neonates) aims to prevent and reduce neurocognitive and motor deficits in high-risk neonates.
The objective of the B.R.A.I.N. program is to identify and prevent brain injury early in high-risk neonates through state-of-the-art diagnostic techniques and neuroprotective care. An interdisciplinary team of medical professionals meets every week to strategize individualized comprehensive neuroprotective plans for infants enrolled in B.R.A.I.N.
Though standard vital monitoring techniques used in NICUs such as blood pressure, heart rate and pulse oximetry provide valuable information about the infant’s hemodynamic status, such standard monitoring techniques don’t provide real-time information regarding the brain’s oxygenation saturation, oxygenation extraction and perfusion status of a sick neonate.
This is where infrared spectroscopy (NIRS) monitoring comes in. “This technology allows us to monitor cerebral oxygenation in very sick infants,” Ramani said. It is a non-invasive method that can be used continually at the bedside as well as during surgery to monitor the health of the brain. It can also be combined with amplitude-integrated electroencephalography (aEEG) to monitor cerebral electrical activity and to diagnose seizures in sick neonates in real-time.
“With the two NIRS devices donated by the Israel family, we are now able to monitor the brain health and adjust our therapies and strategies in real-time on our patients,” Ramani said.