NSAIDs Linked to Acute Kidney Injury in Dehydrated Kids

Yael Waknine

February 04, 2013

Commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) can lead to acute kidney injury (AKI) in pediatric patients, particularly those suffering from dehydration, suggest the results of a retrospective study published online January 28 in the Journal of Pediatrics.

Reviewing charts for 1015 cases of pediatric AKI treated at the Riley Hospital for Children in Indianapolis, Jason M. Misurac, MD, from the Indiana University School of Medicine in Indianapolis, and colleagues found that 27 cases (2.7%) were linked to preadmission NSAID use, including 21 instances of acute tubular necrosis and 6 instances of acute interstitial nephritis.

Symptoms on presentation pointing to dehydration included vomiting (74%), decreased urine output (56%), and diarrhea (26%).

The majority of patients (78%) had been using NSAIDs for less than 7 days, and many used ibuprofen (67%), naproxen (11%), or ketorolac (7%). Data available for 75% of patients showed that most had received an appropriate dose (75%).

Although none of the youngsters died or developed permanent kidney failure,30% had evidence of mild chronic kidney damage persisting after recovery from the acute episode.

"NSAIDs are perhaps the most common avoidable AKI risk to which children are regularly exposed," the authors write, suggesting that renal function be evaluated before NSAID administration.

"In the outpatient setting, this would not be feasible, but with increasing recognition of NSAIDs as a cause of AKI and the pathophysiologic understanding of NSAID-associated AKI, ascertainment of renal function may be indicated before NSAID administration to inpatients," the authors suggest.

Young Children Affected More Severely

Although the majority of patients were teenagers (median age, 14.7 years; range, 6 months - 17.7 years), AKI effects were particularly severe among children younger than 5 years. Younger patients were more likely than their older counterparts to require peritoneal dialysis (100% vs 0%; P < .001) and intensive care unit admission (75% vs 9%; P = .013), resulting in a longer hospital stay (median, 10 vs 7 days; P = .037).

Although the reason remains unknown, the authors surmise that young children may have an increased susceptibility to NSAID-related nephrotoxicity.

"Providers should continue to provide careful NSAID education to parents and children," advised Dr. Misurac in a news release.

Risk for Nephrotoxicity Underestimated, Researchers Say

According to the authors, the prevalence of NSAID-related nephrotoxicity may be higher than reported.

"[I]t should be noted that in our population, many patients who were deemed to have developed multifactorial AKI (and thus were not included in the case definition of NSAID-associated AKI) did have NSAID exposure as one of their multiple risk factors for AKI," write Dr. Misurac and colleagues.

The study was limited by its retrospective nature, which hindered the researchers' ability to draw conclusions regarding the temporal connection between NSAID exposure and AKI onset. In addition, the majority of children included in the study had been otherwise healthy, and few serum creatinine levels had been previously drawn. The very presence of an acute illness causing dehydration is also a confounding factor in the development of AKI.

"However, given the proposed mechanism of NSAID-associated AKI, it is likely that NSAID use played an important role," the authors conclude.

The authors have disclosed no relevant financial relationships.

J Pediatr. Published online January 28, 2013. Full text