Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes
Authors: Sage R. Myers, Nicole S. Glaser, Jennifer L. Trainor, Lise E. Nigrovic, Aris Garro, Leah Tzimenatos, Kimberly S. Quayle, Maria Y. Kwok, Arleta Rewers, Michael J. Stoner, Jeff E. Schunk, Julie K. McManemy, Kathleen M. Brown, Andrew D. DePiero, Cody S. Olsen, T. Charles Casper, Simona Ghetti, Nathan Kuppermann
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Acute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear. <h3>Objective</h3> To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA. <h3>Design, Setting, and Participants</h3> This cohort study was a secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a prospective, multicenter, randomized clinical trial comparing fluid protocols for pediatric DKA in 13 US hospitals. Included DKA episodes occurred among children age younger than 18 years with blood glucose 300 mg/dL or greater and venous pH less than 7.25 or serum bicarbonate level less than 15 mEq/L. <h3>Exposures</h3> DKA requiring intravenous insulin therapy. <h3>Main Outcomes and Measures</h3> AKI occurrence and stage were assessed using serum creatinine measurements using Kidney Disease: Improving Global Outcomes criteria. DKA episodes with and without AKI were compared using univariable and multivariable methods, exploring associated factors. <h3>Results</h3> Among 1359 DKA episodes (mean [SD] patient age, 11.6 [4.1] years; 727 [53.5%] girls; 651 patients [47.9%] with new-onset diabetes), AKI occurred in 584 episodes (43%; 95% CI, 40%-46%). A total of 252 AKI events (43%; 95% CI, 39%-47%) were stage 2 or 3. Multivariable analyses identified older age (adjusted odds ratio [AOR] per 1 year, 1.05; 95% CI, 1.00-1.09;<i>P</i> = .03), higher initial serum urea nitrogen (AOR per 1 mg/dL increase, 1.14; 95% CI, 1.11-1.18;<i>P</i> &lt; .001), higher heart rate (AOR for 1-SD increase in<i>z</i>-score, 1.20; 95% CI, 1.09-1.32;<i>P</i> &lt; .001), higher glucose-corrected sodium (AOR per 1 mEq/L increase, 1.03; 95% CI, 1.00-1.06;<i>P</i> = .001) and glucose concentrations (AOR per 100 mg/dL increase, 1.19; 95% CI, 1.07-1.32;<i>P</i> = .001), and lower pH (AOR per 0.1 increase, 0.63; 95% CI, 0.51-0.78;<i>P</i> &lt; .001) as variables associated with AKI. Children with AKI, compared with those without, had lower scores on tests of short-term memory during DKA (mean [SD] digit span recall: 6.8 [2.4] vs 7.6 [2.2];<i>P</i> = .02) and lower mean (SD) IQ scores 3 to 6 months after recovery from DKA (100.0 [12.2] vs 103.5 [13.2];<i>P</i> = .005). Differences persisted after adjusting for DKA severity and demographic factors, including socioeconomic status. <h3>Conclusions and Relevance</h3> These findings suggest that AKI may occur more frequently in children with greater acidosis and circulatory volume depletion during DKA and may be part of a pattern of multiple organ injury involving the kidneys and brain.