Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes

Abstract

IMPORTANCEAcute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear. OBJECTIVE To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA. DESIGN, SETTING, AND PARTICIPANTSThis 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. EXPOSURES DKA requiring intravenous insulin therapy. MAIN OUTCOMES AND MEASURES 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. RESULTS 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. (continued) Key Points Question What are the mechanisms, risk factors, and outcomes associated with acute kidney injury (AKI) during pediatric diabetic ketoacidosis (DKA)? Findings In this cohort study using data from 1359 DKA episodes in a large, multicenter, prospective study of fluid treatment during DKA, AKI occurred in 43% of episodes and was associated with greater acidosis and greater circulatory volume depletion. 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 c...

Portending Complications in Pediatric Diabetic Ketoacidosis

“…Studies have shown the association of higher initial serum urea nitrogen, higher heart rate, higher glucose-corrected sodium and glucose concentrations, and lower pH with AKI. 11 , 13 , 14 In the present study, the authors found older age, presence of infection, and worse biochemical profile at presentation (lower pH, higher blood glucose, higher lactate, higher corrected sodium, and hyperchloremia) to be associated with AKI. These are quite similar to other studies reiterating the fact that volume depletion at the time of presentation is an important contributor to AKI.…”

“… 11 , 12 The largest cohort study to date was a secondary analysis of data from the PECARN DKA FLUID study in which AKI occurred in 584/1,359 DKA episodes (43%). 13 …”

Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis

“… 17 A recent study demonstrated that children with AKI had lower scores on short-term memory tests during DKA and lower scores on neurocognitive testing, 3–6 months after recovery from DKA, implying that mechanisms for the development of both these complications are probably similar. 6 Among the therapeutic variables such as fluid rate and rate of fall of glucose, our study failed to identify any significant risk factors on multivariate analysis, which predisposed to the development of organ dysfunction. It would be interesting to see the relationship of inflammatory markers and their role in the development of organ dysfunction in DKA.…”

Tubular injury in diabetic ketoacidosis: Results from the diabetic kidney alarm study

“…In line with these data, we found that copeptin concentrations were elevated during DKA and that lower venous pH associated with higher copeptin concentrations. This is particularly important considering that pH is one of the main risk factors for the development of AKI during DKA 39 …”