AWAKEN: Recurrent Neonatal AKI Linked To Longer Hospital Stay Than Single Episode

Austin Rutledge, DO

Credit: Medical University of South Carolina

Findings from a recent study are calling attention to the dangers of recurrent neonatal acute kidney injury (AKI), highlighting a longer length of hospital stay among neonates with multiple episodes of AKI compared to those experiencing a single episode.¹

The secondary analysis of the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study suggests recurrent AKI in neonates is an important clinical distinction warranting careful monitoring, further identifying younger gestational age, lower birthweight, and a more severe initial AKI episode as risk factors for recurrent AKI.¹

Neonatal kidneys are especially susceptible to hypoperfusion and ischemia secondary to postnatal, dynamic changes in renal blood flow, making AKI common among neonates. Despite its high incidence, increased risk among several subpopulations has prompted further investigation into its epidemiology.³

The largest epidemiological evaluation of AKI in neonates to date, AWAKEN’s initial objectives were to validate the definition of neonatal AKI, identify risk factors for AKI, and determine whether neonatal AKI is associated with a longer length of hospital stay and increased mortality. Results were first reported in 2017 and marked the first major multicenter effort to examine AKI in newborns.^1,2

“What we didn't know from the original data was if these babies had experienced one or multiple episodes of AKI,” lead investigator Austin Rutledge, DO, neonatal and perinatal medicine fellow at the Medical University of South Carolina, said in a press release.² “So we didn’t know if the ones who had multiple AKIs had a greater chance of death or if one AKI was enough to adversely affect outcomes.”

To determine whether neonates with multiple episodes of AKI are at risk for worse outcomes compared to neonates with a single episode, investigators compared medical record data for neonates < 14 days of age who were admitted between January 1 and March 31, 2014, to 24 participating level II to IV neonatal intensive care units and received intravenous fluids for ≥ 48 hours. Neonates with congenital heart disease requiring surgery within the first week of life, lethal chromosomal anomalies, death within 48 hours of admission, or severe congenital kidney abnormalities were excluded from the analysis.¹

Comparisons were made among neonates with no AKI, a single AKI episode, and recurrent AKI. Initial AKI was diagnosed by modified, neonatal Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine or urine output criteria, while recurrent AKI was defined using KDIGO serum creatinine criteria. Of note, recurrent AKI could only be diagnosed after serum creatinine level returned to at least the lowest baseline value used to diagnose the prior AKI episode during the same hospitalization.¹

The primary outcome was mortality during the index birth hospitalization. The secondary outcome was length of hospital stay, determined from birth until hospital discharge.¹

The study cohort comprised 2162 neonates, 1233 (57.0%) of whom were male. Gestational age distribution was < 29 weeks for 276 (12.8%) neonates, 29 to < 36 weeks for 958 (44.3%), and ≥ 36 weeks for 928 (42.9%).¹

In total, 605 (28.0%) neonates had ≥ 1 episode of AKI: 472 (78.0%) had a single episode and 133 (22.0%) had recurrent AKI, ranging from 2-11 episodes with a median of 1 (Interquartile range [IQR], 1-2) AKI episode per patient. There was no difference in the median time to the initial AKI episode for those with single AKI (3 days; IQR, 2-7) compared with recurrent AKI (4 days; IQR, 2-11) (P = .10).¹

Compared to those with a single episode of AKI, investigators observed a greater incidence of recurrent AKI among neonates with the youngest gestational age (85 vs 46; P < .001), lowest birthweight (72 vs 47; P < .001), and more severe initial AKI episode (210 vs 75). Infants with recurrent AKI experienced significantly longer median length of hospital stay (60 days; IQR, 25-109) compared to single AKI (18 days; IQR, 9-45).¹

Further analysis revealed recurrent AKI was independently associated with a lower hazard of discharge and thus longer length of hospital stay (Adjusted hazard ratio [aHR], 0.7; 95% CI, 0.6-0.9; P = .01) when compared with those with a single AKI episode. Investigators noted both recurrent (aHR, 4.9; 95% CI, 2.0-12.0; P < .001) and single episode AKI (aHR, 3.6; 95% CI, 2.0-6.4; P < .001) were associated with an increased hazard of death when compared with no AKI, but there was no significant difference in mortality between groups (aHR, 1.4; 95% CI, 0.6-3.0; P = .44).¹

“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.² “Our goal is for every baby who has had kidney injury to be monitored regularly for kidney health.”

References:

1. ^{Rutledge AD, Griffin RL, Vincent K, et al. Incidence, Risk Factors, and Outcomes Associated With Recurrent Neonatal Acute Kidney Injury in the AWAKEN Study. JAMA Netw Open. 2024;7(2):e2355307. doi:10.1001/jamanetworkopen.2023.55307}
2. ^{Medical University of South Carolina. Even with resolution, acute kidney injury in newborns can be life-threatening from very first episode. EurekAlert! February 8, 2024. Accessed February 26, 2024. https://www.eurekalert.org/news-releases/1033927}
3. ^{Coleman C, Tambay Perez A, Selewski DT, Steflik HJ. Neonatal Acute Kidney Injury. Front Pediatr. 2022;10:842544. doi:10.3389/fped.2022.842544}