NEWS | December 4, 2020

Kidney and brain injuries linked to diabetic ketoacidosis

Multiple organ injury link may also offer path to finding better treatments

(SACRAMENTO)

A multi-center research study led by UC Davis Health experts has identified factors that make children with diabetic ketoacidosis (DKA) more likely to experience acute kidney injury. 

A study led by UC Davis Health researchers identified a pattern of multiple-organ injury in pediatric patients who suffered diabetic ketoacidosis. A study led by UC Davis Health researchers identified a pattern of multiple-organ injury in pediatric patients who suffered diabetic ketoacidosis.

The researchers also found that children who experience acute kidney injury are more likely to experience subtle cognitive impairment and demonstrate lower IQ scores. They said the findings indicate a pattern of multiple-organ injury from DKA, which is a serious but common complication of type 1 diabetes. The results may also eventually lead to new options and better treatments for diabetic ketoacidosis.  

The study, “Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes,” was published online today in JAMA Network Open

“A number of recent studies have shown that organ injuries in children with diabetic ketoacidosis occur more frequently than we previously thought,” said Nicole Glaser, a professor of pediatrics whose main clinical focus is type 1 diabetes in children. “We now know that acute kidney injury commonly occurs in children with DKA. And we’ve also found lower IQ scores and worse memory in children who have suffered DKA. Together, it strongly suggests an underlying physiological cause that connects these injuries across the body.” 

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 representing more severe cases of kidney injury, either stage 2 or 3. Children with kidney injuries also 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. The differences persisted even after adjusting for the severity of DKA and demographic factors such socioeconomic status. 

 “We wanted to look at these issues in a more prospective manner,” said Sage Myers, an attending physician in the Emergency Department at Children’s Hospital of Philadelphia and first author of the study. “With 13 participating emergency departments in the Pediatric Emergency Care Applied Research Network [PECARN], we had the ability to not only study the frequency of acute kidney injury in these children but 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.” 

Having the data from DKA cases evaluated prospectively in hospitals across the country represents the gold standard in research information. It offers a reliable pathway to pursue further studies. And that could provide better treatment guidance for clinicians and more hope for children with diabetes and their families. 

“If we can identify how kidney injury occurs during diabetic ketoacidosis, it can help in the development of new therapeutic and preventive strategies,” said Nathan Kuppermann, 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." 

In addition to co-authors Glaser, Myers and Kuppermann, other PECARN study authors were 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, and Simona Ghetti. 

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant U01HD062417) and the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau, Health Resources and Services Administration.