Abstract
Acute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear. To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA. 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. DKA requiring intravenous insulin therapy. 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. 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; P = .03), higher initial serum urea nitrogen (AOR per 1 mg/dL increase, 1.14; 95% CI, 1.11-1.18; P < .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P < .001), higher glucose-corrected sodium (AOR per 1 mEq/L increase, 1.03; 95% CI, 1.00-1.06; P = .001) and glucose concentrations (AOR per 100 mg/dL increase, 1.19; 95% CI, 1.07-1.32; P = .001), and lower pH (AOR per 0.1 increase, 0.63; 95% CI, 0.51-0.78; P < .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]; P = .02) and lower mean (SD) IQ scores 3 to 6 months after recovery from DKA (100.0 [12.2] vs 103.5 [13.2]; P = .005). Differences persisted after adjusting for DKA severity and demographic factors, including socioeconomic status. 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.
Highlights
Among 1359 diabetic ketoacidosis (DKA) episodes, acute kidney injury (AKI) occurred in 584 episodes (43%; 95% CI, 40%-46%)
Multivariable analyses identified older age, higher initial serum urea nitrogen (AOR per 1 mg/dL increase, 1.14; 95% CI, 1.11-1.18; P < .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P < .001), higher glucose-corrected sodium (AOR per 1 mEq/L increase, 1.03; 95% CI, 1.00-1.06; P = .001) and glucose concentrations (AOR per 100 mg/dL increase, 1.19; 95% CI, 1.07-1.32; P = .001), and lower pH (AOR per 0.1 increase, 0.63; 95% CI, 0.51-0.78; P < .001) as variables associated with AKI
Children who had AKI were more likely to have subtle cognitive impairment during DKA and lower IQ at longer-term follow-up. Meaning These findings suggest that AKI is frequent in pediatric DKA and there is a pattern of multiorgan dysfunction during childhood DKA with the possibility of common pathophysiologic mechanisms
Summary
Recent studies have shown that the incidence of organ injuries in children with diabetic ketoacidosis (DKA) is substantially higher than previously appreciated.[1,2,3,4] Subtle cerebral injuries occur commonly in children with DKA, which result in long-term cognitive alterations.[1,2,3,4] the mechanisms of cerebral injury in DKA are under investigation, evidence supports a role for hypoperfusion and reperfusion injury as well as cerebral inflammation associated with DKA in children.[5,6,7,8,9]One recent study demonstrated that acute kidney injury (AKI) commonly occurs in children with DKA. In that study,[10] AKI was reported to be more common in children with low serum bicarbonate levels, tachycardia, and hypernatremia, suggesting that severe dehydration and acidosis may play roles in triggering kidney injury. These risk factors are similar to those associated with cerebral injury during DKA,[11,12,13] raising the question of whether factors associated with DKA severity are independently associated with increased risk of injury to multiple organs, or whether kidney and cerebral injuries during DKA might involve a single pathophysiological process. Isolated cases of severe multiple organ dysfunction syndrome during DKA have been reported[14]; a pathophysiological connection between DKA-related kidney injury and injury to the brain or other organs has not previously been established, to our knowledge
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