Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery

Abstract

Background: Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS).

Methods: This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥ 3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥ 2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI.

Results: One hundred fifty-four children (median age 20.4 months, IQR 2.3-59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥ 3 nephrotoxins. The most commonly administered medications were ketorolac (n = 74, 48.1%), aspirin (n = 62, 40.3%), ibuprofen (n = 51, 33.1%), vancomycin (n = 39, 25.3%), piperacillin/tazobactam (n = 35, 22.7%), and enalapril (n = 14, 9.1%). AKI occurred more commonly in those exposed to ≥ 3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR = 1.2, 95% CI 0.9-1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p = 0.78).

Conclusions: Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.

Keywords: AKI; Acute kidney injury; Congenital cardiac surgery; Nephrotoxin.