Late onset neonatal acute kidney injury: results from the AWAKEN Study

Abstract

Background: Most studies of neonatal acute kidney injury (AKI) have focused on the first week following birth. Here, we determined the outcomes and risk factors for late AKI (>7d).

Methods: The international AWAKEN study examined AKI in neonates admitted to an intensive care unit. Late AKI was defined as occurring >7 days after birth according to the KDIGO criteria. Models were constructed to assess the association between late AKI and death or length of stay. Unadjusted and adjusted odds for late AKI were calculated for each perinatal factor.

Results: Late AKI occurred in 202/2152 (9%) of enrolled neonates. After adjustment, infants with late AKI had higher odds of death (aOR:2.1, p = 0.02) and longer length of stay (parameter estimate: 21.9, p < 0.001). Risk factors included intubation, oligo- and polyhydramnios, mild-moderate renal anomalies, admission diagnoses of congenital heart disease, necrotizing enterocolitis, surgical need, exposure to diuretics, vasopressors, and NSAIDs, discharge diagnoses of patent ductus arteriosus, necrotizing enterocolitis, sepsis, and urinary tract infection.

Conclusions: Late AKI is common, independently associated with poor short-term outcomes and associated with unique risk factors. These should guide the development of protocols to screen for AKI and research to improve prevention strategies to mitigate the consequences of late AKI.

Trial registration: ClinicalTrials.gov NCT02443389.

Conflict of interest statement

Potential Conflict of Interests: The authors have no conflicts of interest relevant to this article to disclose

Figures

Figure 1.. Participant Flow Diagram in Late AKI: screening and enrollment.

Late AKI was defined as occurring after 7 days after birth using serum creatinine data alone. The No AKI group included those with early AKI but not late AKI and those with insufficient data to diagnose AKI. Subjects could be excluded for multiple reasons.

Figure 2.. Survival outcomes in late AKI for the whole cohort and by stages of AKI.

Survival curve for late AKI (A) and by stages of AKI (B) in the whole cohort. Survival was lower in the group with late AKI and in highest stages of AKI.

Figure 3.. Perinatal factors that are associated with increased/decreased risk of late acute kidney injury by gestational age group.

In panel A, the white arrow contains factors associated with reduced odds and black arrow contains factors associated with increased odds for late AKI. In panel B, the white Venn diagram demonstrates unique and overlapping factors within each of the gestational age cohorts associated with late AKI. The black Venn diagram (panel C) displays those risk factors associated with late AKI.

Figure 4.. Relationship between late AKI prevalence and serum creatinine monitoring for the whole cohort and by gestational age group.

Correlation between prevalence of late AKI at each individual study site and frequency of serum creatinine monitoring, represented by the median number of creatinine counts: whole group (A), 22-28 wk group (B), 29-35 wk group (C), and ≥36 wk group (D). There is a direct relationship between the number of serum creatinines and late AKI prevalence in the youngest gestational age cohort (r = 0.58, p=0.003).