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Severe Acute Kidney Injury and Mortality in Extremely Low Gestational Age Neonates
Sangeeta Hingorani1,2,3, Robert H Schmicker2, Patrick D Brophy4
1Division of Nephrology, Seattle Children's Hospital and University of Washington, Seattle, Washington.
Insights
Severe acute kidney injury (AKI) is common in extremely low gestational age neonates. This condition, particularly stage 3 AKI, significantly increases the risk of death, even when identified seven days prior.
Area of Science:
- Neonatal Medicine
- Pediatric Nephrology
- Critical Care Medicine
Background:
- Acute kidney injury (AKI) is linked to adverse outcomes in neonates.
- The incidence, timing, and mortality impact of AKI in extremely low gestational age neonates remain unclear.
Purpose of the Study:
- To investigate the frequency and timing of AKI in extremely low gestational age neonates.
- To determine if AKI is an independent cause of mortality in this vulnerable population.
Main Methods:
- Analysis of 900 neonates from the Preterm Epo Neuroprotection study.
- Comparison of baseline characteristics by AKI severity.
- Cox regression models used to assess the association between severe AKI and death, accounting for confounders and time-dependent AKI status.
Main Results:
- 19% of neonates experienced severe AKI; 7% had stage 3 AKI.
- Stage 3 AKI occurring 7 days before death was independently associated with mortality (HR 3.88).
- Late severe AKI (days 14-28) showed a strong association with increased hazard of death (HR 4.57).
Conclusions:
- Severe AKI is a frequent complication in extremely low gestational age neonates.
- Stage 3 AKI is significantly associated with mortality.
- The association between AKI and death is evident even when AKI is diagnosed up to 7 days before death.
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.
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