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acute kidney injury

Neonatology

Study Identifies Noninvasive Marker for Risk of Acute Kidney Injury

Dr. Christine Stoops is a neonatologist and the leader of the Baby NINJA team at Children’s of Alabama.

The leaders of an innovative project at Children’s of Alabama are looking to add a strategy that could help them identify an acute kidney injury (AKI) earlier.

The Baby Nephrotoxic Injury Negated by Just-in-Time Action, or Baby NINJA, project at Children’s of Alabama was established in 2015 to reduce the use of nephrotoxic medications and monitor neonates for early signs of AKI, which is a common complication in the Neonatal Intensive Care Unit (NICU) because very low birthweight infants are typically exposed to nephrotoxic medications during their stay. In Baby NINJA’s first 18 months, this first-of-its-kind program—which has now been validated at other major children’s hospitals—led to a 42% drop in nephrotoxic medication exposure and a 78% drop in AKI prevalence, according to Baby NINJA team leader Christine Stoops, D.O., M.P.H. The improvements have continued through 2022.

Stoops, a neonatologist at Children’s, hopes recent research will lead to even better outcomes for Children’s patients. In 2019 and 2020, Stoops worked with investigators at Cincinnati Children’s Hospital to see if a noninvasive urinary marker, neutrophil gelatinase-associated lipocalin (NGAL), could provide an earlier warning sign of AKI. The results of the study, which was funded by the National Institutes of Health, were strong, and Stoops hopes Children’s will ultimately be able to incorporate NGAL into its Baby NINJA program.

NGAL can provide a timely way to predict which babies are at risk of AKI because it accumulates in the kidney tubules and urine after an injury, such as those caused by nephrotoxic medications. Studies in other settings show that NGAL elevations occur a couple of days before changes in serum creatinine, which is the traditional method of screening for AKI. But serum creatinine involves a needle stick and waiting for lab results. By the time babies show high levels of creatinine, they are already far along in the AKI. NGAL, in addition to being an earlier marker of AKI, is noninvasive, requiring just a few drops of urine. “The benefits of a noninvasive marker for kidney injury are a win all around for our babies, their families and the caregivers,” Stoops said.

In the NGAL study, researchers obtained daily creatinine and urine samples from 148 NICU babies for up to seven days after they were exposed to nephrotoxic medication, plus two days after they stopped the medication and/or when their AKI resolved. They identified the positive and negative predictive values of NGAL for AKI, confirming the results with the creatinine test. Stoops hopes the study and others like it will lead to FDA approval of NGAL as a test for AKI so Children’s of Alabama can incorporate its use into their Baby NINJA program and the very tiny babies in the NICU will receive far fewer blood draws.

January 16, 2023 by childrensal

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.

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.”

February 15, 2022 by childrensal

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

August 27, 2021 by childrensal

Cardiology, Inside Pediatrics, Nephrology

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

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).

January 16, 2020 by childrensal

Neonatology

Baby NINJA: Reducing Acute Kidney Injury One Preemie at a Time

Up to 87% of very low-birthweight infants in the neonatal intensive care unit (NICU) are exposed to at least one nephrotoxic medication during their stay. About 1 in 4 of those experience at least one episode of acute kidney injury (AKI), which can lead to increased length of stay and mortality. [1], [2], [3] There is also evidence that even a single incidence of AKI increases the risk of chronic kidney disease.[4]

To address this problem, in 2015 Children’s of Alabama began the first initiative in the country designed to reduce the use of nephrotoxic medications in the NICU. The initiative, called “Baby NINJA,” was so successful it is now being validated at several other major children’s hospitals.

The effort builds off the NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) project, a joint endeavor between Children’s and the Cincinnati Children’s Hospital Medical Center that started in 2011 in non-critically ill children. The goal was to ensure that children only receive the nephrotoxic medications that they needed for as long as they needed them, and that their kidney function was closely monitored for any signs of AKI.

The NINJA initiative reduced exposure to nephrotoxic medications by 38% and concomitant AKI by 64%.[5] As a result, last year it was added to the Solutions for Patient Safety consortium and instituted at 147 children’s hospitals worldwide.

The Baby NINJA project at Children’s has demonstrated similarly stellar outcomes, noted Christine Stoops, D.O., assistant professor of pediatrics at the University of Alabama at Birmingham (UAB) and the primary investigator on the initiative. In the 18 months after implementing the program, nephrotoxic medication exposure dropped 42% and AKI prevalence fell 78%, she said. Meanwhile, the rate of patients with AKI who had also been exposed to nephrotoxic medications fell 64%, while patients spent 68% fewer days in AKI.

The program’s key players are the two NICU pharmacists, Sadie Stone, PharmD, and Emily Evans, PharmD, who round daily with the multidisciplinary team, which includes neonatologists and nurse practitioners, to identify at-risk babies, Stoops said. Once identified, a magnet is put on the patient room entryway denoting that the the infant is on “NINJA Watch,” which serves as a reminder to closely review medications. “The success of the program is due to in large part to the strong pharmacist support,” she said.

The pharmacists review a screening report of patients with high NTM exposure each morning and manually verify the exposure. Infants with a high exposure then receive a daily serum creatinine test during and for two days post-exposure or post-AKI resolution, whichever occurred last. During this time, the team discusses possible alternative medications, drug dosages, timing of drug levels, and hydration status. Previously, the infants would have only received the test every three to five days.

“It tells the neonatologist that this kidney is at risk of injury and makes everyone ask, ‘are these the medications the baby needs? Could we adjust them, even if we just reduce the dose? How do we reduce the risk of AKI if they really do need these medications?’” Stoops said. Often, she said, “It’s just a simple act of being mindful about what you’re doing.”

The NINJA program is now being rolled out throughout Children’s in other intensive care units, and validated at Cincinnati Children’s Hospital.

Help for Children With Kidney Disease

Learn about the Pediatric and Infant Center for Acute Nephrology at Children’s of Alabama.

[1] Rhone ET, Carmody JB, Swanson JR, Charlton JR. Nephrotoxic medication exposure in very low birth weight infants. J Matern Fetal Neonatal Med. 2014;27(14):1485-90.

[2] Jetton J, Boohaker L, K Sethi S, Wazir S, Rohatgi S, Soranno D, et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. The Lancet Child & Adolescent Health. 2017;1(3):184-94.

[3] Askenazi DJ, Griffin R, McGwin G, Carlo W, Ambalavanan N. Acute kidney injury is independently associated with mortality in very low birthweight infants: a matched case-control analysis. Pediatr Nephrol. 2009;24(5):991-7.

[4] Menon S, Kirkendall ES, Nguyen H, Goldstein SL. Acute kidney injury associated with high nephrotoxic medication exposure leads to chronic kidney disease after 6 months. J Pediatr. 2014;165(3):522-7 e2.

[5] Goldstein SL, Mottes T, Simpson K, et al. A sustained quality improvement program reduces nephrotoxic medication-associated acute kidney injury. Kidney Int. 2016;90(1):212-21.

August 20, 2019 by childrensal