Acute Kidney Injury Frequent in Kids With Diabetic Ketoacidosis

Veronica Hackethal, MD

March 13, 2017

Of children with type 1 diabetes who were hospitalized for diabetic ketoacidosis (DKA), 64% developed acute kidney injury (AKI), according to a new study published online March 13 2017 in JAMA Pediatrics.

The work is the first to show that acute kidney injury is a frequent complication of pediatric DKA. The latter can be life-threatening and represents the leading cause of hospitalization in youth with type 1 diabetes.

This high percentage is concerning because acute kidney injury is associated with increased morbidity and mortality. Studies have also suggested that it may increase the risk of later chronic kidney disease, a condition for which youngsters with type 1 diabetes are already at increased risk.

Results also showed that patients with severe acidosis and profound volume depletion were at increased risk of severe acute kidney injury. In DKA, high blood glucose levels can lead to increased urination and volume depletion. Patients also have acidosis and increased production of ketoacids.

"On presentation to the hospital, many children with DKA present quite volume depleted, but fluid management" must by necessity be a fine balancing act "because of the risk for cerebral edema," which represents the most serious complication of DKA and can lead to death, senior author Dina Panagiotopoulos, MD, of the University of British Columbia, Vancouver) told Medscape Medical News via email.

Acidosis, Tachycardia, Hypernatremia Associated With AKI

For the study, the Canadian doctors reviewed the medical records of 165 youth aged 18 years and younger with type 1 diabetes admitted for DKA to British Columbia Children's Hospital in Vancouver between September 2008 and December 2013.

They defined acute kidney injury using Kidney Disease/Improving Global Outcomes (KDIGO) serum creatinine criteria.

Because no children in this study had baseline creatinine values but they were all considered to be healthy, the researchers approximated these, using height and an estimated glomerular filtration rate of 120 mL/min/1.73m2. They also did more conservative analyses using an eGFR of 90 mL/min/1.73m2, the lower limit of normal kidney function.

Results showed that 64.3% (n=106) of youth hospitalized for DKA developed acute kidney injury. Of these, 34.9% had stage 1, 48.3% had stage 2, and 19.8% had stage 3 acute kidney injury.

Using the more conservative estimate of baseline kidney function instead indicated that 41.8% (n=61) of children had acute kidney injury, 53.6% of whom had mild kidney injury and 46.4% had severe.

Worse acidosis — having a serum bicarbonate level less than 10 mEq/L — was significantly and independently associated with severe acute kidney injury, with a five-times increased odds compared with ≥10 mEq/L (adjusted odds ratio [aOR], 5.22).

Tachycardia was also similarly associated with acute kidney injury. For each 5 beats/minute increase in heart rate, the odds of severe acute kidney injury increased by 22% (aOR, 1.22).

The same was true of hypernatremia — having an initial corrected sodium of 145 mEq/L or more was linked to three-times increased odds of mild acute kidney injury, compared with 135 to 144mEq/L (aOR, 3.29).

No children died and none developed cerebral edema. However, two required renal dialysis.

In an accompanying comment, Benjamin Laskin, MD, MS, of the Children's Hospital of Philadelphia, Pennsylvania, and Jen Goebel, MD, of Children's Hospital Colorado, Aurora, agree with the study authors that great care is needed when considering fluid administration in these children.

Because of severe hyperglycemia and derangements in sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, they reiterate.

"While awaiting more research to determine the sweet spot for fluid management in children with acute kidney injury, it seems reasonable to give fluids to patients with acute kidney injury secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output."

Reference Card, Computer System, May Help Management

One reason acute kidney injury may be underrecognized in pediatric DKA is because children's weight and height need to be considered when interpreting serum creatinine levels, which increase with acute kidney injury.

"From this study, we became aware that recognizing acute kidney injury is a challenge, because serum creatinine needs to be interpreted in the context of a child's height," Dr Panagiotopoulos commented.

"As a result of our findings, we are developing a quick reference card that provides clinicians with a formula utilizing the child's height to determine what their expected normal baseline creatinine would be prior to illness," she explained.

The quick reference card also has clinical definitions for different stages of acute kidney injury, as well as recommendations for clinical monitoring and management of children with the condition.

The reference card also has information on when it is deemed necessary to refer to nephrology — 42% of the patients with acute kidney injury in this study did not have a documented creatinine level prior to hospital discharge and did not have nephrology follow-up, a fact that Drs Laskin and Goebel say is "alarming."

Dr Panagiotopoulos said her clinic has also now created a computerized system that tracks serum creatinine after discharge and flags abnormal values that need further evaluation and referral to nephrology.

Drs Laskin and Goebel acknowledge, however, that it "remains unknown which children with resolved acute kidney injury should be referred to nephrology for ongoing care."

Dr Panagiotopoulos says her team has started a second study to look at the long-term impact of acute kidney injury and the subsequent risk for developing chronic kidney disease.

The authors report no relevant financial relationships. Dr Laskin reports a grant from the National Institutes of Health; Dr Goebel has no relevant financial relationships.

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JAMA Pediatr. Published online March 13, 2017. Article, Editorial

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