Ibuprofen Use in Children Linked to Hospital-Acquired Kidney Injury

A study found that ibuprofen use was associated with an increased risk of hospital-acquired kidney injury among children.

Led by Licong Su, MD, National Clinical Research Center for Kidney Disease, Nanfang Hospital, China, the investigative team evaluated a total of 50,420 hospitalized children.

“Although ibuprofen is the most commonly prescribed nonsteroidal anti-inflammatory drugs (NSAID) in the world, few large studies have specifically studied the association between ibuprofen and hospital-acquired AKI in children,” wrote the investigators.

“Furthermore,” they continued, “these studies were generally limited by a small sample size and reported inconsistent findings.”

Ibuprofen and Acute Kidney Injury

All children were drawn from a cohort of the Epidemiology of AKI in Chinese Hospitalized Patients (EACH) study, a multicenter retrospective study of 3, 044, 023 patients.

Patients were admitted to third-tier medical centers in China between January 1, 2013 — December 31, 2015.

Using electronic health records of the participating centers, the investigators obtained relevant patient data.

“Hospitalized children aged 1 month to 18 years who had prescriptions and a certain number of serum creatinine (SCr) tests were included,” they noted.

“Children with end-stage renal disease, community-acquired AKI, low baseline SCr level (<10 μmol/L), high standardized baseline SCr level (>4 times the sex- and age-specific reference value), or missing diagnosis code were excluded.”

They defined acute kidney injury (AKI) as an increase in SCr level of 26.5 μmol/L or higher within 48 hours or by 50% or more over the baseline value. Their definition was in accordance with the Kidney Disease: Improving Global Outcomes guidelines.

Thus, the mean age of the population was 5.0 years, and the majority (60.8%) was male.

Furthermore, of the population, 11.0% used ibuprofen and 6.9% developed hospital-acquired AKI during hospitalization.

Following adjustment for confounders, the investigators found that ibuprofen use was associated with a statistically significant increased risk of hospital-acquired AKI (hazard ratio [HR], 1.23; 95% CI, 1.14-1.34).

Additionally, ibuprofen use was associated with a greater hazard in children with chronic kidney disease (HR, 2.31; 95% CI, 1.73-3.10) compared to those without it (HR, 1.19; 95% CI, 1.09-1.29).

Increased hazard linked to ibuprofen was also noted for children who required intensive care (HR, 1.47; 95% CI, 1.24-1.75) versus those who did not (1.18; 95% CI, 1.07-1.29).

Children who were >10 years old had an HR of 1.64 (95% CI, 1.32-2.05]), children who were >1 year – 10 years had an HR of 1.36 (95% CI, 1.23-1.52), and children who were 1 month – 1 year had an HR of 0.99 (95% CI, 0.86-1.13).

And finally, the team noted that the association of ibuprofen with risk of hospital-acquired AKI was dose-dependent—according to their dose-response analysis.

Conclusion

The investigators cautioned for physicians to be judicious in prescribing ibuprofen among this population. They also encouraged close monitoring of kidney function in such patients.

“The exact mechanisms for these interactions were not clear,” they noted.

“Children with chronic kidney disease may have an elevated in vivo drug concentration, and children with more risk factors for developing AKI may be more susceptible to the potential nephrotoxic effect of ibuprofen."

They acknowledged that their study was limited by the lack of long-term data in the population as well as ethnic diversity.

“As in all other association studies, this study may still have unknown confounders, and causal inference is not possible,” they concluded.

The study, “Association of Ibuprofen Prescription with Acute Kidney Injury Among Hospitalized Children in China,” was published online in JAMA Network Open.