Summary: Children who experience kidney damage as a result of diabetic ketoacidosis are more likely to develop cognitive impairments and demonstrate lower IQ scores.
Researchers from a consortium of hospitals including Children’s Hospital of Philadelphia (CHOP) have identified factors that make children with diabetic ketoacidosis more likely to experience acute kidney injury. Analyzing data from a large, multicenter clinical trial, the researchers also found that children who experience acute kidney injury are more likely to also experience subtle cognitive impairment and demonstrate lower IQ scores, suggesting a pattern of multiple organ injury.
The findings were published online today in JAMA Network Open.
Multiple recent studies have shown that organ injuries in children with diabetic ketoacidosis occur more frequently than previously thought. One recent retrospective study found that acute kidney injury commonly occurs in these children. Earlier analysis of a large, multicenter study demonstrated cerebral injury commonly occurs in diabetic ketoacidosis. Together, these studies raised the possibility of an underlying pathophysiology that connects these injuries across the body if the presence of these injuries were linked in patients.
“We wanted to look at these issues in a more prospective manner,” said Sage Myers, MD, an attending physician in the Emergency Department at CHOP and first author of the study. “With 13 participating emergency departments in the Pediatric Emergency Care Applied Research Network, we had the ability to not only study the frequency of acute kidney injury in these children, but also the underlying factors associated with injury and whether there is an association between the occurrence of acute kidney injury and cerebral injury, which would suggest a possible linkage between the mechanisms of injury underlying both.”
The researchers studied 1,359 episodes of diabetic ketoacidosis in children. Acute kidney injury occurred in 584 (43%) of those episodes, and 252 of those episodes (43%) were classified as either stage 2 or 3, representing more severe cases of kidney injury.
When assessing whether acute kidney injury was associated with cognitive issues, children with kidney injuries had lower scores on short-term memory tests during diabetic ketoacidosis, as well as lower IQ scores three to six months after recovering from the condition. These differences persisted after adjusting for the severity of diabetic ketoacidosis and demographic factors like socioeconomic status.
“If we can identify the mechanisms of kidney injury after diabetic ketoacidosis, it can help in the development of new therapeutic and preventive strategies,” said Nathan Kuppermann, MD, professor and chair of emergency medicine at UC Davis Health, and senior author and co-principal investigator of the study. “We’re also hoping to focus future research on how diabetic ketoacidosis causes simultaneous, multi-organ injuries such as what we demonstrated in this study.”
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Acute Kidney Injury During Diabetic Ketoacidosis in Children: Frequency, Risk Factors, and Association with Neurocognitive Outcomes
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.
Design, Setting, and Participants
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.
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.
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.
Conclusions and Relevance
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.