Even once resolved, acute kidney injury in newborns can be life-threatening from the first episode.

Our resilient kidneys are invaluable members of the body’s purification system and excellent at bouncing back from injury. This is even true for most sick infants in the neonatal intensive care unit. Because of this remarkable ability, declines in kidney function in infants have often been historically overlooked in favor of other pressing illnesses or symptoms.

But doctors and researchers have shown increased interest in understanding the kidney health of newborns and young infants over the past decade, leading to the AWAKEN (Assessment of Worldwide Acute Kidney Epidemiology in Neonates). With initial results reported in 2017, AWAKEN was the first major multicenter effort to examine acute kidney injury, or AKI, in newborns.

In a recently published follow-up analysis of AWAKEN data in Open JAMA Network, Austin Rutledge, DO, a neonatal and perinatal medicine researcher at the Medical University of South Carolina, led a multicenter team to examine the impact of repeated episodes of AKI in hospitalized infants. Their work was done on behalf of the Neonatal Kidney Collaborative, a nonprofit group of pediatric neonatologists and nephrologists working to reduce the burden of kidney disease in newborns.

The original AWAKEN study showed that 30% of the approximately 2,000 babies studied had AKI and that having AKI was associated with a four times higher risk of death.

Heidi Steflik, MD, MSCR, a neonatologist at MUSC and one of the principal investigators of the recent report, noted that the AWAKEN study found that kidney disease was not only very common in newborns, but contributed also independently to infant mortality. In other words, it is not simply an incidental result or an indicator of another disease.

“But what we didn’t know from the original data was whether these babies had experienced one or more episodes of AKI,” Rutledge added. “So we didn’t know if those with multiple AKIs had a greater risk of death or if a single AKI was enough to harm outcomes.”

The research team re-examined the AWAKEN data to see whether certain groups of infants were more prone to repeated episodes and whether these repeated incidents increased the risk of death or other adverse outcomes. The MUSC researchers collaborated with Russell Griffin, Ph.D., a statistician at the University of Alabama at Birmingham, and with researchers at several other medical centers.

They combed through the data by hand to determine which babies with AKI in 24 neonatal intensive care units across the country had had one or more occurrences, using newly defined criteria to make the call. They looked at characteristics such as gestational age, birth weight and initial stage of AKI, as well as outcomes such as risk of death and length of hospitalization.

They found that a large proportion of babies with AKI had recurrences: of the 605 infants with AKI, 133 had more than one episode. But the mortality rate increases with any AKI, from the very first episode.

“Because the kidneys tend to rebound, AKI has sometimes been neglected in the past,” Steflik explained. “But we found that even a single episode of AKI is dangerous.”

Other episodes did not add additional risk of death but were associated with longer hospital stays for these children, some of whom were in the NICU for months. Additionally, the long-term effects of these injuries are still under investigation.

Similar results were found in a separate study of MUSC patients in 2020-2021.

Based on these findings, Rutledge and Steflik suggest that initial and recurrent episodes of AKI merit careful monitoring and management as well as further study.

“Kidney health is something that has been underestimated across the board, but especially in babies,” Steflik said. “We’re really excited to be one of the groups paying attention to this.”

Looking to the future, Rutledge explained that researchers are looking for better ways to detect and measure AKI, because the current measurement – ​​serum creatinine level – has a delay before showing positivity. There is also interest in learning more about the duration of AKI as well as the long-term impacts on children.

“As we continue to study the long-term effects of AKI, we want families and parents to understand how important it is to follow up with a nephrologist after a NICU stay.” , Rutledge said. “Our goal is for every baby with kidney injury to be monitored regularly for their kidney health.”