DKA, AKI, and Cognitive Harms: Triple Threat to Kids

Kids’ brains may suffer following episodes of acute kidney injury (AKI) during diabetic ketoacidosis (DKA), a new study suggested.

Children who had AKI saw poorer marks on short-term memory testing during DKA as measured by digit span recall testing compared with children who didn’t have an AKI event (mean digit span recall 6.8 vs 7.6, P=0.02), Sage Myers, MD, MSCE, of Children’s Hospital of Philadelphia, and colleagues reported.

As shown in their study online in JAMA Network Open, these possible neurological harms also lingered for months afterwards, as kids with an AKI event during DKA also had on average lower IQ scores 3 to 6 months after recovery measured by the Wechsler Abbreviated Scale of Intelligence (100.0 vs 103.5, P=0.005).

Of note, these short-term memory and IQ differences remained even after adjustment for the severity of the DKA episode and demographics such as the child’s socioeconomic status.

For the study, which was conducted across 13 U.S. hospitals and formulated as a secondary analysis of the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) study, the researchers assessed 1,359 episodes of DKA.

All occurred in children younger than age 18 (mean age of 11.6) with a blood glucose level of 300 mg/dL or greater and venous pH less than 7.25 or serum bicarbonate level less than 15 mEq/L.

About half of these episodes occurred in patients with new-onset diabetes, the investigators noted. AKI occurred in 43% of these episodes, yielding a total of 584 cases. Of these cases, 252 (43%) were classified as stage 2 or 3.

The original study randomized patients to one of four fluid therapies to resolve DKA:

• Fast rehydration with 0.45% sodium chloride (NaCl)

• Fast rehydration with 0.9% NaCl

• Slow rehydration with 0.45% NaCl

• Slow rehydration with 0.9% NaCl

Certain factors were predictive of a child experiencing AKI during DKA, the researchers reported. Some of these included being older (adjusted odds ratio per 1 year older 1.05, 95% CI 1.00-1.09, P=0.03), having a higher initial serum urea nitrogen (AOR per 1 mg/dL increase 1.14, 95% CI 1.11-1.18, P<0.001), and having a higher heart rate (AOR for 1-SD increase in z-score 1.20, 95% CI 1.09-1.32, P<0.001).

Other metabolic factors were also tied to a higher chance of AKI occurring during a DKA episode: having higher glucose-corrected sodium (AOR per 1 mEq/L increase 1.03, 95% CI 1.00-1.06, P=0.001) and glucose concentrations (AOR per 100 mg/dL increase 1.19, 95% CI 1.07-1.32, P=0.001), and lower pH (AOR per 0.1 increase 0.63, 95% CI 0.51-0.78, P<0.001).

“We wanted to look at these issues in a more prospective manner,” Myers explained in a statement. “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.”

Also speaking to the background of the study, co-author Nathan Kuppermann, MD, of the University of California, Davis School of Medicine, pointed out that identifying mechanisms of kidney injury after DKA can also aid in the development of new therapeutic and preventive strategies.

“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,” he said.