Severe Acute Kidney Injury and Mortality in Extremely Low Gestational Age Neonates

Abstract

Background and objectives: AKI is associated with poor short- and long-term outcomes. Questions remain about the frequency and timing of AKI, and whether AKI is a cause of death in extremely low gestational age neonates.

Design, setting, participants, & measurements: The Recombinant Erythropoietin for Protection of Infant Kidney Disease Study examines the kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo Neuroprotection study, a randomized, placebo-controlled trial of recombinant human erythropoietin. We included 900 of 941 patients enrolled in Preterm Epo Neuroprotection. Baseline characteristics were compared by primary exposure (severe AKI versus none/stage 1 AKI) using unadjusted logistic regression models. Cox regression models estimated the relationship between severe AKI and death after adjustment for potential confounders. Time-dependent AKI was modeled as a binary outcome and a categorical variable by stage of AKI. We fit Cox models using time-dependent AKI status lagged by <7 days before death. Landmark analyses examined the relationship of death with development of severe AKI.

Results: Severe AKI occurred in 168 of 900 (19%, 95% confidence interval, 17% to 20%) neonates, and stage 3 AKI occurred in 60 (7%, 95% confidence interval, 5% to 8%). Stage 3 AKI occurring 7 days before death (hazard ratio, 3.88; 95% confidence interval, 1.26 to 11.96), intraventricular hemorrhage (hazard ratio, 2.01; 95% confidence interval, 1.01 to 3.99) and sepsis (hazard ratio, 2.85; 95% confidence interval, 1.12 to 7.22) were all independently associated with death. Severe AKI occurring 7 days before death (hazard ratio, 2.21; 95% confidence interval, 0.92 to 5.26) was associated with death but not statistically significant. In a landmark analysis, after adjusting for potential confounders, late (after day 14 and before day 28) severe AKI was strongly associated with higher hazard of death (hazard ratio, 4.57; 95% confidence interval, 1.82 to 11.5).

Conclusions: Severe AKI occurs frequently in extremely low gestational age neonates. Stage 3 AKI is associated with mortality, and this association is present 7 days before death.

Trial registration: ClinicalTrials.gov NCT01378273.

Keywords: acute kidney injury; gestational age; mortality; neonatal; pediatric nephrology.

Copyright © 2021 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Consort diagram of study cohort. ELGAN, extremely low gestational age neonate.

Figure 2.

Hazard ratio of mortality (y axis) associated with development of AKI by stage and by severe AKI before day of death (day 0; x axis).