Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study

Abstract

Introduction: In adults, small (< 50%) serum creatinine (SCr) increases predict mortality. It is unclear whether different baseline serum creatinine (bSCr) estimation methods affect findings of acute kidney injury (AKI)-outcome associations. We characterized pediatric AKI, evaluated the effect of bSCr estimation approaches on AKI-outcome associations and evaluated the use of small SCr increases to predict AKI development.

Methods: We conducted a retrospective cohort database study of children (excluding postoperative cardiac or renal transplant patients) admitted to two pediatric intensive care units (PICUs) for at least one night in Montreal, QC, Canada. The AKI definition was based on the Acute Kidney Injury Network staging system, excluding the requirement of SCr increase within 48 hours, which was impossible to evaluate on the basis of our data set. We estimated bSCr two ways: (1) the lowest SCr level in the three months before admission or the average age- and gender-based norms (the standard method) or (2) by using average norms in all patients. Outcomes were PICU mortality and length of stay as well as required mechanical ventilation. We used multiple logistic regression analysis to evaluate AKI risk factors and the association between AKI and mortality. We used multiple linear regression analysis to evaluate the effect of AKI on other outcomes. We calculated diagnostic characteristics for early SCr increase (< 50%) to predict AKI development.

Results: Of 2,106 admissions (mean age ± SD = 5.0 ± 5.5 years; 47% female), 377 patients (17.9%) developed AKI (using the standard bSCr method) during PICU admission. Higher Pediatric Risk of Mortality score, required mechanical ventilation, documented infection and having a bSCr measurement were independent predictors of AKI development. AKI was associated with increased mortality (adjusted odds ratio (OR) = 3.7, 95% confidence interval (95% CI) = 2.1 to 6.4, using the standard bSCr method; OR = 4.5, 95% CI = 2.6 to 7.9, using normative bSCr values in all patients). AKI was independently associated with longer PICU stay and required mechanical ventilation. In children with no admission AKI, the initial percentage SCr increase predicted AKI development (area under the curve = 0.67, 95% CI = 0.60 to 0.74).

Conclusions: AKI is associated with increased mortality and morbidity in critically ill children, regardless of the bSCr used. Paying attention to small early SCr increases may contribute to early AKI diagnosis in conjunction with other new AKI biomarkers.

Figures

Figure 1

Study inclusion and exclusion criteria flowchart. This flowchart illustrates the inclusion and exclusion criteria used to screen patients from both study centers to derive the final study population. 1Centre Hospitalier Universitaire Ste-Justine (CHUSJ) original exclusion criteria were < 3 days of age or < 40 weeks of gestation, > 18 years of age, pregnancy or postpartum admission, admission for renal transplantation, brain death at entry into the pediatric intensive care unit (PICU), expected PICU stay < 24 hours, a priori decision to withhold or withdraw treatment and end-stage renal failure. hrs = hours; Jan = January; MCH = Montreal Children's Hospital; Sep = September.

Figure 2

Difference between last PICU SCr and baseline SCr based on AKI status. Boxplots illustrating (a) percentage differences between last pediatric intensive care unit (PICU) serum creatinine (SCr) and baseline SCr (bSCr) and (b) raw differences (in μmol/L) between last PICU SCr and bSCr levels in patients who survived through PICU discharge and in whom at least one SCr measurement was performed. Boxplots are presented according to Acute Kidney Injury Network (AKIN) staging system status from no acute kidney injury (AKI) (far left) to AKIN stage 3 (far right). A nonparametric Kruskal-Wallis test was used to evaluate significant differences across the four groups.

Figure 3

Day of PICU admission when AKI first occurred at the Montreal Children's Hospital center. Histograms of patients with acute kidney injury (AKI) depicting the number of patients who first developed AKI on each day of pediatric intensive care unit (PICU) admission. Data are representative of only the Montreal Children's Hospital center.

Figure 4

Association of PICU length of stay and mechanical ventilation duration with increasing AKI severity. Histogram illustrating (a) duration (in days) of pediatric intensive care unit (PICU) stay and (b) duration (in days) of mechanical ventilation in patients with no acute kidney injury (AKI) or Acute Kidney Injury Network (AKIN) stage 1 to 3 AKI. White bars represent Centre Hospitalier Universitaire Ste-Justine (CHUSJ) data, gray bars represent Montreal Children's Hospital (MCH) data and black bars represent all data. A nonparametric Kruskal-Wallis test was used to evaluate significant differences across the four AKI severity strata.

Figure 5

Predicting AKI using PICU admission day 1 percentage SCr increase in patients without admission AKI. Area under the receiver operating characteristic curve (ROC) demonstrating the ability of first pediatric intensive care unit (PICU) admission day of percentage serum creatinine (SCr) increase from baseline to predict future acute kidney injury (AKI) development after PICU admission day 1. This analysis includes only patients with no AKI on PICU admission day 1 who had their SCr levels measured on PICU admission day 1. Only patients from the Montreal Children's Hospital are included in this analysis.