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nephrology

Inside Pediatrics, Nephrology

Neonatal Kidney Collaborative Advances Understanding of Acute Kidney Injury

David Askenazi, M.D., is a pediatric nephrologist at Children’s of Alabama and a professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

David Askenazi, M.D., is a pediatric nephrologist at Children’s of Alabama and a professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

A bunch of pediatric nephrologists and neonatologists walk into a National Institutes of Health meeting on neonatal acute kidney injury (AKI) in 2013. The punchline? They are inspired to form the Neonatal Kidney Collaborative (NKC) with the clever website address of babykidney.org.

“At that NIH meeting, we recognized that bringing people to work together on multicenter studies was a critical step in moving the field forward,” said Children’s of Alabama pediatric nephrologist David J. Askenazi, M.D., one of the founding members and current NKC Board chair.

Today, the collaborative boasts 77 participating institutions with 168 members and 19 published manuscripts. Several of those publications come from the group’s inaugural study called AWAKEN (Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates), the first multinational, multicenter study on neonatal AKI.

The study involved a retrospective review of three months of data on 2,162 infants in Level 2 or 3 neonatal intensive care units in four countries, a third of whom had AKI. The investigators found those with AKI were 4.6 times more likely to die and stayed in the hospital an average of 8.8 days longer than those without. Other results from AWAKEN include risk factors for mortality and the development of AKI (such as low albumin and hemoglobin levels) and hypo- and hypernatremia, as well as a link between intraventricular hemorrhage (bleeding in the brain) and AKI.

“We chose the name AWAKEN because we felt like the field needed to be awakened,” Dr. Askenazi said. And it’s worked, he said, with the number of studies, initiatives and young people interested in neonatal nephrology growing exponentially.

The collaborative, he said, “not only provides opportunities to study neonatal kidney disease, but we also have committees to address the educational, advocacy, and research needs of this evolving field.”

The group recently received a significant research grant from Nuwellis, a global company focused on fluid management solutions for pediatric and adult patients, to perform the ALMOND (Assessing Longitudinal Micropreemie Outcomes in Neonates at Risk for Renal Disease) study. “This research effort will expand our understanding of neonatal kidney disease in extremely premature neonates who were enrolled in a multicenter trial called PENUT (Preterm Erythropoietin Neuroprotection Trial),” he said.

The study will use the PENUT database, which contains thousands of clinical data points and hundreds of thousands of urine biomarker data points from more than 900 babies. “It’s a goldmine,” said Dr. Askenazi. “It will allow the NKC to pose and answers questions about kidney disease in extremely premature neonates, including whether caffeine, commonly prescribed to these infants, can prevent AKI; determine the fluid provision to improve clinical outcomes; and identify additional risk factors for neonatal AKI, among other questions.”

“The work of this collaborative is contagious, and it drives me,” he said. “It makes me want to continue to help move the field forward and support young doctors who are filled with energy and excitement.”

Inside Pediatrics, Nephrology

Tracking Kidney Transplant Rejection in the Blood and Urine 

Michael Seifert, M.D., is a pediatric nephrologist at Children’s of Alabama and an associate professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Michael Seifert, M.D., is a pediatric nephrologist at Children’s of Alabama and an associate professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Children who receive kidney transplants at Children’s of Alabama undergo a routine biopsy six months after the procedure to look for signs of rejection. In about 20 percent of patients, those signs are there, even if their blood and urine tests look normal. “On the flip side,” said Children’s pediatric nephrologist Michael E. Seifert, M.D., “that means about 80 percent of our patients are getting biopsies that are normal.” 

The holy grail, then, would be a non-invasive biomarker test using blood or urine that can identify kidney transplant injury without needing a biopsy — which is exactly what Dr. Seifert and his lab are working on. Their research relies on a biorepository of patients’ blood, urine, and kidney biopsy tissue collected throughout and after the transplant process. 

One of the blood tests they’re working on uses technology originally developed to screen maternal blood for signs of fetal abnormalities. The test looks for cell-free DNA, or cfDNA, which comes from the fetus and differs from maternal DNA. Since transplanted kidneys also have DNA different from the patient’s own kidney, “you can look in the bloodstream for the proportion of the DNA coming from the transplant versus the normal background from the recipient’s non-transplant cells,” Dr. Seifert said. High levels of cfDNA is a sign of acute kidney injury that could be due to rejection.  

Studies in adults validate this as a good method to detect rejection. “But the problem is, those are done in adults whose native kidneys would be roughly similar in size to the transplant they’re carrying,” Dr. Seifert said. Children often have a much larger, adult-sized transplant compared to the size of their native kidneys, so the cutoff levels used for diagnosing rejection in adults may not work in children. “We’re trying to make these existing diagnostic tests more pediatric specific,” he said. 

The story is different for urinary biomarkers. It’s been known for years that the kidney releases certain proteins when it’s injured. Tests to detect those proteins, however, can take days. But a new device called SimplePlex, currently available only in the research setting, can measure several of these proteins at one time in a single sample in less than an hour.   

“We’re looking at ways to get this technology closer to the clinic, so you’re not just profiling kidney transplant patients’ risk for injury based on their standard blood tests like creatinine, but you’re also adding these additional biomarkers that can tell you more information about what’s happening inside the organ,” Dr. Seifert said.  

Being able to determine via blood and urine tests who needs a biopsy and who doesn’t would have a huge impact for pediatrics, particularly at Children’s, where these biopsies are done on a universal basis, he said. Ideally, the tests could also provide information on the underlying cause of the rejection. For instance, the cfDNA test is good at picking up antibody-mediated rejection, but not as good at recognizing cell-mediated rejection. The urine biomarkers are good at identifying both rejection types, but not at identifying rejection related to viral infections. 

“Once we understand more about the clinical scenarios in which the biomarkers perform well,” said Dr. Seifert, “we’ll be able to design interventional trials to treat the patient based on the biomarker changes rather than just the standard clinical tests such as creatinine.”  

Inside Pediatrics, Nephrology

Childhood Household Dysfunction Predicts Hypertension, Vascular Injury in Adolescents 

Dan Feig, M.D., Ph.D., is a pediatric nephrologist at Children’s of Alabama and a professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Dan Feig, M.D., Ph.D., is a pediatric nephrologist at Children’s of Alabama and a professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Verbal and physical abuse; neglect; and household dysfunction such as divorce, domestic violence, and poverty in early childhood (called adverse childhood experiences, or ACEs) affect approximately 25 percent to 30 percent of children in the United States. They also put those children at significantly increased risk for health issues like hypertension and cardiovascular disease as adults.  

“Ideally, we would like to prevent neglect, maltreatment, abuse, and household dysfunction,” said Children’s of Alabama pediatric nephrologist Daniel Feig, M.D., Ph.D. “But until that can be achieved, we need to work on mitigating their long-term effects.” Dr. Feig’s work looks at whether experiences have already changed the vascular function of individuals exposed to ACEs and whether those changes are reversible.  

“We want to see if there’s a detectable signal, something that puts them in the risk category for future disease and identify those who would benefit from intervention or therapy,” he said. 

Dr. Feig and his team used validated questionnaires to screen 78 teens for the three types of ACEs: abuse, neglect, and household dysfunction. Nearly 70 percent had been exposed to at least one ACE. The investigators also tracked the adolescents’ blood pressure with a 24-hour continuous ambulatory blood pressure monitor; measured their pulse wave velocity (a marker of blood vessel elasticity and reactivity); and looked for markers of inflammation and increased vascular tone in their bloodwork. 

They found that compared to teens with no exposure or with exposure to abuse and neglect, individuals exposed to household dysfunction had a significantly higher 24-hour diastolic blood pressure without the normal drop that occurs at night. They also found a significantly increased baseline inflammatory state. Those who experienced sexual abuse had substantially altered pulse wave velocity, which meant their blood vessels were stiffer. Despite these changes, the children had normal blood pressure. 

“This tells us that even as early as 10 to 12 years after exposure there are detectable alterations in vascular biology associated with the ACEs,” Dr. Feig said. “These individuals might benefit from interventions to reverse or slow those changes to prevent the progression of hypertension and the later risk of cardiovascular disease.” 

The team expected to see more changes in children with a history of exposure to abuse. Dr. Feig hypothesizes that the chronic nature of household dysfunction may be behind the vascular changes. “Things that reset the biology of the vessels are slow and steady effectors,” he said. “That can be dietary, that can be obesity, that can be emotional stressors, or chronic inflammation. I think that the household dysfunction category might have a greater continuous effect as opposed to episodes of horrific injury.” 

The next step is to intervene with medications to try and reduce inflammation and prevent the progression of vascular dysfunction.  

The group is currently following the study participants and hope to secure funding for larger longitudinal studies. 

Inside Pediatrics, Nephrology

Overflow at Children’s of Alabama’s Dialysis Unit

As the only pediatric dialysis unit in the state, Children’s of Alabama’s hemodialysis unit is used to being busy. But with COVID-19, “Our census has doubled,” said Children’s nephrologist Sahar Fathallah-Shaykh, M.D. One reason is that transplants were paused during the height of the pandemic, leaving many children who might have been able to stop dialysis forced to continue.  

Another reason is that more infants born with chronic kidney disease (CKD) are surviving because of new equipment capable of providing them dialysis. “We have seen many patients with CKD surviving who, just a few years ago, had no chance of surviving,” Dr. Fathallah-Shaykh said. Because these infants are so small, they must come to the hospital up to five times a week for the procedure, compared to three times a week for older children. Once infants are older, the team tries to transition them to peritoneal dialysis at home; but babies may have medical contraindications that require continuing on hemodialysis. 

The impact on the staff is significant, she said. “It’s a challenge.” Dialysis charge nurse Suzanne White, RN, ECP agrees. “It takes a lot of coordination to schedule treatments for 18 patients,” she said, particularly when treatment times last up to four hours. “Our days last 10 to 12 hours,” she said. 

One reason caring for infants on dialysis calls for intense attention, said Dr. Fathallah-Shayk, is that “nurses are at the bedside the entire time monitoring these babies. Babies move a lot, and if they move, the dialysis may not work as well.” The nurses console the babies, try to distract them and sometimes even hold them while they are dialyzed.  

The team includes a child life specialist who also tries to distract the infants during dialysis; social workers who support the families, including coordinating transportation and ensuring families keep their appointments; a dietician to help with nutrition and ensure proper growth; and a pharmacist to help with medications. “We all work as a team to make this happen,” Dr. Fathallah-Shayk said, “otherwise we couldn’t do it.”  

And, said White, “we have a good support system from the administration on down,” which helps avoid burnout. The unit also added more staff in anticipation of continued growth. “We are trying to coordinate their care to the best of our ability, troubleshoot and really communicate and work with each other,” she said. 

Inside Pediatrics, Nephrology

Welcoming the new PRISMAX Dialysis Machines to the PICU & CVICU

When you’re talking about continuous dialysis and plasmapheresis for sick kids, you want state-of-the-art technology. And that’s just what Children’s of Alabama got this year when hospital administrators approved a significant investment in the newest generation of the PRISMAX system for the Pediatric and Infant Center for Acute Nephrology (PICAN).  

The PICAN team is no stranger to these therapies; after all, the team has provided them for more than 500 children for over 10,000 days since 2013 in the pediatric, neonatal and cardiac intensive care units. In 2020, the newest PRISMAX became available, and Children’s became the first hospital in the state and one of the first children’s hospitals in the country to receive the new machines, said David Askenazi, M.D., who directs the PICAN. “We are very grateful to the hospital for making this available to us and our patients,” he said. “We know that patients will benefit.” 

But first, everyone had to be trained to use the new machines. While it sounds like replacing the old with the new should be a relatively simple switch, the staff required intense education. 

“The educational part of the rollout was very important,” said acute dialysis coordinator Daryl Ingram, RN, BSN, CDN. “We had to make sure the nurses and physicians were comfortable with them before they started using them on patients.” He was pleasantly surprised at how the entire team embraced the new technology and the groundbreaking opportunity the new machines offered, he said. 

One reason could be the improvements the new system brought. For instance, nurses no longer have to manually empty 5-liter effluent bags. “It definitely saves time,” said Suzanne Gurosky, RN, ECP, the dialysis charge nurse. She also touted the battery backup in the machines, which enables patients to ambulate and even do physical therapy while still connected. Another plus is the ability of the machines to decipher the cause for an alarm—because someone moved or jostled the fluids, or because there was a real issue going on. That helps avoid disruptive alarms and alarm fatigue. 

It does this through artificial intelligence, “so it understands what’s happening better than it used to,” said Dr. Askenazi.  

The new PRISMAX also sports improved safety features, such as correcting itself for fluid removal. In addition, it provides extensive data that can be integrated into the department’s quality-improvement initiatives. “We’re excited to dig into that information and incorporate it into our practice,” said Dr. Askenazi.  

After the training and the successful integration of the new PRISMAX machines into the unit, there was one more thing the team needed to do: name them. “We like to name our machines to help the kids feel more comfortable,” said Ingram. The winners were Rosie, Max, and Astro from the old “The Jetsons” cartoon, Johnny 5 from the movie “Short Circuit,” and C3PO from, of course, “Star Wars.” 

Inside Pediatrics, Nephrology

COVID-19 Infection May Leave Kids with Kidney Problems

Although children were far less likely to contract COVID-19 during the early days of the pandemic, they were affected. As of July 1, 2021, the American Academy of Pediatrics and the Children’s Hospital Association reported more than 4.04 million children had been diagnosed with COVID-19 in the United States; 50,439 in Alabama.1 Since the pandemic’s start, Children’s of Alabama has treated over 500 infants and children with COVID-19 and almost 100 with multisystem inflammatory syndrome (MIS-C), the long-term repercussions of which are just now emerging. 

Many affected children, like adults, have developed acute kidney injury (AKI) during hospitalization for severe disease, particularly children who have been hospitalized with MIS-C. One study of 152 children who had either acute COVID-19 or MIS-C found that AKI occurred in 10 percent of patients. These children had longer lengths of stay in the hospital and increased risk of other medical conditions.2 Another study of 52 patients with COVID-19 found that nearly 30 percent developed AKI.3 

“The jury is out on how much of that was due to severe illness versus how much the virus plays a direct role,” said Children’s nephrologist Erica C. Bjornstad, M.D. Some reports surmise that the virus is toxic to the kidney, but, Dr. Bjornstad said, more evidence is needed. Nonetheless, it appears that children who developed AKI while hospitalized need long-term follow-up as the long-term implications are not yet fully understood, she added. 

Thus, primary care physicians caring for these children after discharge should have a “high level of suspicion” if urine tests show high levels of protein, or children demonstrate new onset hypertension,” Dr. Bjornstad said. “They should look for COVID-19 as a culprit.” In fact, she suggests urine tests for all children who had COVID-19, even if they had a mild form of the disease, although no formal guidelines have been released. If the problem doesn’t resolve, the children should be referred to a nephrologist. “We don’t have a good handle if it goes away,” she said.  

“We’re still learning how this plays out since the pandemic is still not over,” Dr. Bjornstad said. Plus, “we don’t know what the fall holds with the Delta variant and as more people move indoors,” she added. 

Dr. Bjornstad and others at Children’s are involved with a large study that is mining an international registry of COVID-19 patients (children and adults) to tease out the effects on the kidney. Ideally, she would like to obtain funding to follow former patients for a prolonged period of time, “so we can keep learning and have data to support standard guidelines,” she said. 


1 Children and COVID-19: State-Level Data Report. American Academy of Pediatrics. July 1, 2021. Available at: https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/. Accessed July 7, 2021.

2 Basalely A, Gurusinghe S, Schneider J, et al. Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19. Clin Invest. 2021;100(1): 138-145

3 Knight, P.P., Deep, A. Save the kidneys in COVID-19. Pediatr Res (2020). https://doi.org/10.1038/s41390-020-01280-x

Cardiology, Inside Pediatrics, Nephrology

Children’s of Alabama Leads Consortium Dedicated to Improving Outcomes in Cardiac Surgery-Acute Kidney Injury

NEPHRON_WEB

Children’s of Alabama is one of 22 hospitals in the U.S. that is a member of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON).

Neonatal acute kidney injury (AKI) occurs in 52 to 64 percent of patients undergoing cardiac surgery (CS) and is associated with increased morbidity and mortality.

However, because CS-AKI rates vary widely between centers, it appears that interventions to prevent or mitigate the condition could reduce the overall rate.

Yet, noted Santiago Borasino, M.D., medical director of Children’s of Alabama’s Cardiovascular Intensive Care Unit (CVICU), “there are critical gaps in our understanding as to how to best define CS-AKI, who is at risk, and which patients could best benefit from interventions to prevent or  mitigate the effects of CS-AKI.”

To improve understanding of CS-AKI in this population, Borasino is one of the leaders of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON), composed of 22 children’s hospitals around the country. The consortium’s goals are to describe neonatal kidney injury epidemiology, evaluate variability in diagnosis and management, identify risk factors, investigate the impact of fluid overload and explore associations with outcomes. It involves multidisciplinary teams including clinicians from cardiac critical care, cardiology, nephrology, and cardiac surgery.

“NEPHRON is providing multicenter data on CS-AKI for the first time,” Borasino said. “The large size of the cohort will enable us to look at details that are not possible with single-center studies.”

NEPHRON published its preliminary results in April 2019, reporting an overall incidence of 54 percent among 2,240 patients in its database.[1] In November 2019, NEPHRON presented additional results during the American Heart Association’s annual meeting, showing a threefold variation in rates among centers, from 27 percent to 86 percent, with significant variations in KDIGO stage (adult AKI definition) to identify AKI (65 percent by oligo oligo-anuria versus 35 percent by creatinine).

The results also showed that the use of cardiopulmonary bypass, but not time spent on bypass, increased the odds of CS-AKI, and that only KDIGO Stage 3 was associated with mortality. There was no impact of CS-AKI on the duration of mechanical ventilation or hospital length of stay.[2]

“NEPHRON preliminary results highlight the limitations of the KDIGO definition and the need to better understand CS-AKI as it occurs with incredible variability among centers, opening the door for future quality improvement intervention,” Borasino said.

The next step is to develop an algorithm to predict which patients are more likely to develop AKI so physicians can intervene earlier. “Early recognition and proper management of AKI are at the forefront of critical care medicine,” said Children’s of Alabama pediatric nephrologist Tennille Webb, M.D. “However, most pediatric hospitals that perform cardiac surgeries do not have protocols in place for managing severe AKI post-operatively.” Webb is now working on developing a clinical pathway to identify patients at increased risk of AKI based on specific patient characteristics. “An advantage to developing this algorithm in the CVICU is that we are able to determine the exact timing and etiology of AKI development in individuals undergoing cardiopulmonary bypass,” she said. “If we can proactively identify risk factors that place these individuals at increased risk for AKI, we can provide earlier intervention, such as early initiation of renal replacement therapy, in an effort to mitigate some of the known severe consequences of AKI.”

“The work that we are doing is very important because we know that AKI post-cardiac surgery leads to worse outcomes and is associated with chronic kidney disease,” Webb said. “It’s great, and yet rare in other institutions, that we have been able to develop a strong relationship between the CVICU and nephrology to work as a cohesive team early AKI detection and prevention.”


[1] Gist KM, Blinder JJ, Bailly D, Neonatal and Paediatric Heart and Renal Outcomes Network: design of a multi-centre retrospective cohort study. Cardiol Young. 2019;29(4):511-518.

[2] Alten J, Cooper DS, Gist KM, et al. , Abstract 13177: Epidemiology of Neonatal Cardiac Surgery Induced Acute Kidney Injury From the Neonatal and Pediatric Heart and Renal Outcomes Network. Circulation. 2019;140(Suppl1).

 

Nephrology

Cutting Out Sugar Intake, One Kid at a Time

The average American consumes almost 152 pounds of sugar a year, about three pounds a week or 42.5 teaspoons a day — more than triple the recommended amount.[1] While sugar consumption isn’t the only cause of the country’s obesity epidemic, it is definitely a major contributing factor — particularly in children. And the problem is not only obesity, says pediatric nephrologist Daniel I. Feig, M.D., Ph.D., who directs the University of Alabama at Birmingham (UAB) Division of Pediatric Nephrology at Children’s of Alabama, but all the downstream health effects of being overweight, including cardiovascular disease, hypertension, liver disease, kidney disease and type 2 diabetes.

One reason for the high sugar intake is economic. Over the past 35 years, the price of fruits and vegetables has tripled, he said, while the price of sugar-sweetened foods such as beverages fell 75%. “The availability of calories and nourishment in a low-sugar fashion is much more expensive than it was a few decades ago,” he said. “We can talk until we’re blue in the face in low-income, urban clinics about eating fruits and veggies, but that isn’t the only barrier to kids not eating them; their families can’t afford it.

Then there’s the issue of high-fructose corn syrup (HFCS), used as a sweetener and preservative in many foods. Research from Feig and others has found that HFCS is not simply sugar in another form but has a high relative fraction of fructose compared to glucose, which alters cellular carbohydrate metabolism. This results in a greater rise in triglycerides and uric acid than with sugar from sugar cane or sugar beets.

Researchers have also demonstrated that high levels of uric acid stiffen and thicken blood vessel walls, resulting in hypertension, as well as activating the renin-angiotensin system system, causing immediate vasoconstriction.

Clinical trials find that lowering uric acid levels in hypertensive adolescents, but not adults, improves blood pressure. “So we have a window of opportunity in children to reduce their long-term cardiovascular and renal risk factors by controlling sugar intake,” Feig said.

That’s why clinicians and nutritionists at the hypertension clinic at Children’s counsel patients and their families about the effects of sugar as well as where the sugar is found (i.e., the sweet tea that is ubiquitous throughout the South). “Adolescents get about 48% of their sugar from sugar-sweetened beverages,” Feig said, “so it isn’t a function of just telling them not to eat candy.”

“When I see a child in our hypertension clinic with obesity-related hypertension, about a third of the time very high sugar and caloric intake in their beverages, up to 2,000 calories a day, is a major contributing factor,” he said. “Simply eliminating those liquids could make a huge difference in their health.”

He cites a recent study that polled new parents about the sugar content of various foods. More than 80% of parents underestimated the sugar content of foods with a “health halo,” like fruit juice and yogurt. “We have an educational deficit in terms of dietary literacy,” he said.

“So a big push in our clinic is helping families learn more about the nutritional content of food.”

Blood Pressure Control

Learn more about the hypertension clinic at Children’s of Alabama.


[1] Department of Health and Human Services. How Much Sugar Do You Eat? You May Be Surprised! https://www.dhhs.nh.gov/dphs/nhp/documents/sugar.pdf.

Nephrology

Children’s of Alabama Becomes First to Safely Provide Dialysis to Tiny Babies

Didactic and hands-on teaching on the use of CRRT using the Aquadex Pureflow.

Despite the frequent use of dialysis for critically ill children and adults, the procedure has historically been used sparingly in neonatal intensive care units (NICU) because dialysis  machines designed for adults can cause severe complications in babies. That’s no longer the case at Children’s of Alabama.

The problem is that continuous renal replacement therapy in these tiny patients requires at least 100 ml of blood to initiate the therapy. This can be half or even more of the baby’s entire blood volume, said David Askenazi, M.D., MSPH, who directs the Pediatric and Infant Center for Acute Care Nephrology. “Many times, when we started the machine, we had to open the crash cart to resuscitate infants who were coding,” he said.

That changed in 2013, when Askenazi realized that a machine designed to remove fluid and sodium from blood in adults with heart failure — the Aquadex FlexFlow® System — could be repurposed for neonate dialysis.

“If we could adapt a machine that requires one-third of the blood of the traditional machine volume to do what we needed, we knew we could improve our ability to support these babies,” he said. So the team learned as much as they could about the device, developed a safety net of processes to maximize the likelihood of success and convinced the hospital to buy its first machine.

Today, the hospital has fiveAquadex machines and two or three babies are typically receiving dialysis at any one time. “Now we have complete control over their fluids, electrolytes and waste products,” Askenazi said, “while the nurses feel comfortable doing the therapy and the babies don’t even know they’re on it.” Last year, babies in the NICU spent a total of 800 days on dialysis compared to just 30 days in 2013.

“For our babies born with diseased or absent kidneys, Aquadex has given them a chance at life,” said NICU nurse practitioner Kara Short, MSN, CRNP, “because in the past, there were no options to treat these patients.”

The team published the results of its first 12 patients in the journal Pediatric Nephrology in 2016. Since then, they have treated more than 90 patients, the smallest just 1.2 kg (2 pounds, 7 ounces) and taught nephrologists at several other children’s hospitals around the country to use the Aquadex. However, there are still only a handful of hospitals offering the procedure.

“We have shown we can now support these babies safely,” Askenazi said. “The impetus now is on us to make sure the patients who can benefit from this therapy make it to Children’s so we can give them a chance for life.”

And the machine’s manufacturer? It is now pursuing a pediatric indication for Aquadex.

A Team Effort

Learn more about the neonatology program and team at Children’s of Alabama.

Nephrology

Continual Performance Improvement in Pediatric Kidney Transplantation

The renal transplant team at Children’s of Alabama has performed more than 500 kidney transplants since 1968. To this day, continuous improvement remains at the heart of everything it does.

The hospital is part of the Improving Renal Outcomes Collaborative (IROC), a learning health system of 32 pediatric kidney transplant centers in the U.S. that share data and best practices in an effort to improve transplant outcomes.

“We know we can achieve better things more efficiently together than if we’re working individually,” said Children’s pediatric nephrologist Michael E. Seifert, M.D. 

Improvement Projects

One recent project involved improving blood pressure assessments. “We know that if we control blood pressure we get better patient outcomes and the transplant does better,” Seifert said. Yet an analysis of 17 IROC transplant centers found that blood pressure was being measured appropriately based on current guidelines at just 12% of transplant clinic visits.

Each IROC center had the freedom to design custom tools to fit its needs for improving blood pressure measurement. The answer at Children’s was paper-based tracking logs and regular meetings to review progress. The team also educated all staff on the importance of measuring blood pressure and how to measure it according to the most recent guidelines. “It was pretty simple things that, when applied systematically and consistently, led to prolonged improvement,” Seifert said. Today, at least 85% of clinic visits include an appropriately measured blood pressure and the team is working to improve that number.

The next project is to improve adherence to immunosuppressive drugs, a major risk factor for rejection and loss of the kidney transplant. The team is developing a questionnaire for parents and patients so they can identify the barriers to adherence and develop targeted interventions. “We have to get away from an accusatory approach to a partnership and ask, ‘How can we work with you to make it easier to take your medications?’” Seifert said.

Children’s is also a national leader in studying surveillance biopsies to help reduce acute rejection rates. Most pediatric transplant centers do not perform early surveillance biopsies at pre-specified time points because of their invasive nature, but Seifert and his team demonstrated that surveillance biopsies in the first six months after transplant can detect subclinical inflammation, which is associated with a nearly threefold increased risk of acute rejection and allograft failure. Treating patients who demonstrated such inflammation, they recently reported, significantly reduces that risk. Importantly, they also demonstrated that the  surveillance biopsy procedure was safe for pediatric patients, with extremely low rates of mild adverse events.

Bringing the Bench and the Clinic Closer

The transplant team also runs a robust translational research program, with half of transplant patients enrolled in at least one research study. One is a biorepository study in which patients’ blood, urine and kidney biopsy tissue is collected throughout and after the transplant process. “Then we can develop biomarkers of kidney transplant diseases that impact the survival of the transplant,” Seifert said.

The second study will identify determinants of cardiovascular health in pediatric and young adult kidney transplant recipients who have a high burden of cardiovascular risk. “Transplantation improves but doesn’t eliminate this risk,” Seifert said. “This study is

designed to understand certain unique cardiovascular risk factors, such as the impact of

early life stress, on cardiovascular and renal outcomes.”

The Transplant Experts

Learn more about kidney transplantation at Children’s of Alabama.