Browsing Tag

kidney disease

Urology

A new protocol for kidney tests in spina bifida patients

A new study shows that ultrasound is not enough to monitor kidney health in children with spina bifida. (Stock photo)

For decades, doctors have relied heavily on ultrasound scans to monitor kidney health in children with spina bifida, the most common permanently disabling birth defect in the U.S. People with spina bifida tend to develop end-stage renal disease up to 20 years earlier than the general population, so keeping a close watch on kidney health from a young age is important, says Children’s of Alabama pediatric urologist Stacy Tanaka, M.D. “Then if there’s a concern, it can be acted upon early and not ignored.”

Current guidelines from the Spina Bifida Association (SBA) recommend annual screening with ultrasound to look for hydronephrosis—a condition in which the urine backs up into one or more kidneys—as a sign of kidney function, and blood tests like serum creatinine, to measure overall kidney health. But with kids, Tanaka says, “the practice pattern was that a lot of people were only doing renal ultrasound.”

Now a new study from Tanaka and her Children’s colleague David Joseph, M.D., as well as other kidney experts from around the country, shows that ultrasound alone is not enough to assess kidney health. “We basically use ultrasonography as a reflection of renal function,” Joseph said, but few, if any, studies assessed its accuracy in determining renal function.

Stacy Tanaka, M.D.

The study’s genesis came during a multidisciplinary meeting in 2003 of specialists who treat children with spina bifida. “The bottom line from all disciplines at that time was that nobody was really treating this population with evidence-based care,” Joseph said.

To change that, the Centers for Disease Control and Prevention and the SBA established the National Spinal Bifida Patient Registry (NSBPR), to which 20 spina bifida clinics submit data to help develop evidence-based care. In addition, nine clinics established a urologic protocol to manage and preserve initial renal function in young children with spina bifida (UMPIRE). The NSBPR and UMPIRE provided the data set Joseph and Tanaka used to determine the effectiveness of renal ultrasound vs. blood test to assess renal function.

The two registries included data on 2,500 children ages 1-18 with myelomeningocele, the most severe form of spina bifida. All had had an ultrasound and blood test within six months to determine estimated glomerular filtration rate (eGFR), a marker of kidney health.

The results were striking: ultrasound-based detection of hydronephrosis had only about a 25% sensitivity for identifying children with signs of chronic kidney disease in the UMPIRE study and 24% in the NSBPR cohort. That means kidney damage in three out of four children was going undetected. The poor sensitivity held even when researchers looked only at severe hydronephrosis, which had an even worse sensitivity rate–just 6% to 11%. “The renal ultrasound by itself wasn’t all that good,” Joseph said, “but that didn’t surprise us.”

David Joseph, M.D.

The findings challenge current practice and suggest that blood tests measuring kidney function should be routinely performed alongside ultrasound, not just when ultrasound results look concerning, as some clinicians practice. The team at Children’s prefers testing for cystatin C rather than creatinine because of the test’s improved and more accurate ability to obtain an eGFR.

One reason clinicians may eschew blood tests is that it involves needles, Tanaka said, which be traumatizing for children. Ultrasound, on the other hand, is noninvasive, easily available, and can be performed by technicians.

“The ultrasound is very helpful and important,” Joseph said, “but you need to recognize that it may not be telling you about renal function or injury to the kidney.” The findings have already changed practice at Children’s, where all kids with spina bifida now receive both tests during kidney health screening.

Ideally, the next study would randomize kids to either double testing or ultrasound alone, but that requires significant funding, particularly since the children would need to be followed for years.

This study was conducted with very little financial support, Tanaka said. “It represents a labor of love for everyone at all nine UMPRIE centers who have been involved in this project,” Joseph added.

July 25, 2025 by
Nephrology

Studying outcomes in Continuous Renal Replacement Therapy

Children’s of Alabama is part of international research effort designed to improve care for CRRT patients.

With most research that evaluates a vital form of dialysis care in children called continuous renal replacement therapy (CRRT) lacking in size and scope—hampering efforts to glean practice-changing insights—an international effort in which Children’s of Alabama is integral is expected to fill the gap.

Dubbed WE ROCK (Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease), the retrospective study involves a total of nearly 1,000 children treated at 32 centers in seven countries between 2018 and 2021. Representing the largest international registry of children receiving CRRT for acute kidney injury or fluid overload—which can result from a variety of factors, including congenital anomalies, nephrotoxins and others—WE ROCK aims to evaluate the association of factors such as fluid balance and timing of CRRT initiation and duration with patient outcomes.

“It’s so hard to get data of this type, so this study is very significant,” said Children’s of Alabama pediatric nephrologist Tennille Webb, M.D., who’s also assistant director of the Pediatric and Infant Center for Acute Nephrology (PICAN) and an assistant professor of nephrology and pediatrics at University of Alabama at Birmingham (UAB). At Children’s, research nurse coordinator Jessica Potts, RN, is carrying out the crucial task of collecting and analyzing the data.     

Children’s serves as a hub for CRRT care for a high volume of pediatric kidney patients. In the decade-plus between 2013 and mid-2024, 602 patients were treated with CRRT at Children’s. Just over half of CRRT is performed in the neonatal intensive care unit (NICU), while 32% is done in the pediatric intensive care unit (PICU) and the remaining 15% in the cardiovascular intensive care unit (CVICU).

Children’s has long stood out among pediatric hospitals by offering CRRT to the tiniest infants using modified Aquadex equipment. Aquadex had initially been developed for adult patients with heart failure to remove fluid from the heart, but Children’s nephrologist and PICAN director David Askenazi, M.D., seized on the technology’s small filters to adapt it for use in neonates. Now, other centers offer neonatal dialysis with modified Aquadex, as well.

“Other dialysis machines pull a lot of blood out of babies because the filters are so large, which makes everyone nervous,” Webb explained. “CRRT is gentler than hemodialysis because you can remove fluid at a slower rate over an extended amount of time, allowing for fewer fluid shifts and blood pressure swings, especially in those who may have low blood pressure. We’re still meeting our goals, but not being as aggressive.”

The WE ROCK effort has generated at least 10 published manuscripts so far by study collaborators, with the promise of many more to come, Webb says. By looking at outcomes such as major adverse kidney events 90 days after CRRT (including mortality, dialysis dependence, and persistent kidney dysfunction) as well as functional outcomes, investigators should be able to derive data that could change pediatric nephrology practice. 

Insights will be bidirectional: Children’s specialists will learn from other centers, and others will learn from Children’s. Researchers can also determine new questions and angles that fuel future research. It’s an exciting prospect for Webb and her colleagues.

“Having that data from 32 centers, we can see what they’re doing, model it and make some improvements in these patients,” Webb said.

January 8, 2025 by
Nephrology

Testing the first potential treatment for AMKD

Daniel Feig, M.D., Ph.D., and other Children’s researchers are leading a trial that provides hope for patients with AMKD.

A team of clinicians and researchers from Children’s of Alabama and the University of Alabama at Birmingham (UAB) has launched a potentially groundbreaking clinical trial testing the first potential treatment for APOL1-mediated kidney disease, or AMKD, a genetic condition linked to mutations in the APOL1 gene that can lead to rapid kidney function decline and, ultimately, kidney failure.

“The gene itself is involved in activation of inflammatory arms of the immune system,” said Daniel Feig, M.D., Ph.D., a pediatric nephrologist at Children’s. The APOL1 gene variant doesn’t just cause AMKD; it also exacerbates other kidney conditions. “Individuals with focal segmental glomerulosclerosis (scarring in the kidneys), IgA nephropathy, or diabetic nephropathy with APOL1 risk variants progress to end-stage kidney disease much faster than those without the risk variants.”

This genetic factor is particularly common in African Americans, contributing significantly to the higher rates of kidney failure seen in this population, Feig said.

The current trial, called AMPLITUDE, is testing the efficacy and safety of a first-in-its-class oral medication called VX-147, or inaxaplin. The drug is designed to inhibit the inflammatory pathway triggered by the APOL1 gene variant. The hope is that blocking this pathway will slow or even stop the progression of AMKD.

“It’s exciting because these patients have no other options for therapy,” Feig said.

An earlier trial evaluating standard-of-care plus inaxaplin in people with two APOL1 variants showed a nearly 50% reduction in proteinuria (a marker of kidney damage) after 13 weeks of treatment and reduction in scar tissue in the kidneys. The most common side effects were headache, back pain and nausea. The study was published in the New England Journal of Medicine.

The current trial is enrolling about 500 adult and pediatric participants, including about 150 children ages 10 to 18. More than 200 centers in the U.S. and other countries are involved.

Those eligible for the trial must have confirmed AMKD (with two APOL1 variants), proteinuria, and reduced kidney function. Participants will be monitored for two years while taking the study medication.

“If we can slow the disease by a number of years, that means these patients don’t need dialysis, they don’t need transplant, they don’t have the risk of kidney failure and their life expectancy is much, much, much longer,” Feig said. “It offers hope to families that have been having a difficult time and are really frustrated by the lack of alternatives.”

August 7, 2024 by