Long-Term Kidney Outcomes after Pediatric Acute Kidney Injury

Abstract

Key Points:

1. Among 4173 children with AKI, 18% had major adverse kidney events (death, kidney failure, or CKD) during a median 10-year follow-up.

2. AKI survivors were at 2–4 times higher risk of major adverse kidney events, hypertension, and subsequent AKI versus matched hospitalized comparators.

3. This justifies improved surveillance after pediatric AKI to detect CKD and hypertension early and improve long-term kidney health.

Background: AKI is common in hospitalized children. Pediatric AKI receiving acute KRT is associated with long-term CKD, hypertension, and death. We aim to determine the outcomes after AKI in children who did not receive acute KRT because these remain uncertain.

Methods: Retrospective cohort study of all hospitalized children (0–18 years) surviving AKI without acute KRT between 1996 and 2020 in Ontario, Canada, identified by validated diagnostic codes in provincial administrative health databases. Children with prior KRT, CKD, or AKI were excluded. Cases were matched with up to four hospitalized comparators without AKI by age, neonatal status, sex, intensive care unit admission, cardiac surgery, malignancy, hypertension, hospitalization era, and a propensity score for AKI. Patients were followed until death, provincial emigration, or censoring in March 2021. The primary outcome was long-term major adverse kidney events (a composite of all-cause mortality, long-term KRT, or incident CKD).

Results: We matched 4173 pediatric AKI survivors with 16,337 hospitalized comparators. Baseline covariates were well-balanced following propensity score matching. During a median 9.7-year follow-up, 18% of AKI survivors developed long-term major adverse kidney event versus 5% of hospitalized comparators (hazard ratio [HR], 4.0; 95% confidence interval [CI], 3.6 to 4.4). AKI survivors had higher rates of long-term KRT (2% versus <1%; HR, 11.7; 95% CI, 7.5 to 18.4), incident CKD (16% versus 2%; HR, 7.9; 95% CI, 6.9 to 9.1), incident hypertension (17% versus 8%; HR, 2.3; 95% CI, 2.1 to 2.6), and AKI during subsequent hospitalization (6% versus 2%; HR, 3.7; 95% CI, 3.1 to 4.5), but no difference in all-cause mortality (3% versus 3%; HR, 0.9; 95% CI, 0.7 to 1.1).

Conclusions: Children surviving AKI without acute KRT were at higher long-term risk of CKD, long-term KRT, hypertension, and subsequent AKI versus hospitalized comparators.

Graphical abstract

Figure 1

Cumulative probability of MAKE-LT among AKI survivors versus hospitalized comparators. Cumulative probability of MAKE-LT among AKI survivors who did not receive KRT versus hospitalized comparators and dialysis-treated AKI survivors versus hospitalized comparators. MAKE were defined as a composite of all-cause mortality, long-term KRT (long- term dialysis or kidney transplant), or CKD. Dark lines represent AKI survivors who did not receive KRT (solid) versus hospitalized comparators (dashed). Lighter lines represent dialysis-treated AKI survivors (solid) versus hospitalized comparators (dashed). Data for dialysis-treated AKI survivors and their hospitalized controls was reproduced from ref , with permission. MAKE, major adverse kidney event; MAKE-LT, long-term major adverse kidney event.

Figure 2

Smoothed HRs for MAKE-LT among AKI survivors versus comparators, by restricted cubic spline analysis. MAKE were defined as a composite of all-cause mortality, long-term KRT (long-term dialysis or kidney transplant), or CKD. The solid line represents the HR for MAKE over time posthospital discharge. The shaded area represents the pointwise 95% CIs for the corresponding HR. The dashed gray line represents a HR of 1 (i.e., no significant difference in the hazard of MAKE between AKI and comparator individuals). The HR of MAKE decreased over the first approximately 5 years but remained elevated for approximately 16 years postdischarge. The CIs should be interpreted with caution because they are not global CIs and thus not adjusted for multiplicity. CI, confidence interval; HR, hazard ratio.

Figure 3

Cumulative probability of CKD among AKI survivors versus comparators. All CKD diagnoses were incident because individuals with preexisting CKD were excluded from the study.

Figure 4

Cumulative probability of incident hypertension among AKI survivors versus comparators. Incident hypertension was defined as a new diagnosis of hypertension postdischarge in an individual without a diagnostic code for hypertension during a 5-year lookback period before index hospitalization.

Figure 5

Subgroup analyses for MAKE-LT among AKI survivors versus comparators. We evaluated for effect modification on the association between AKI and MAKE among the above subgroups using interaction terms (far right column) and stratified Cox proportional hazard models to determine HR for MAKE among AKI survivors versus hospitalized comparators for each stratum. ICU, intensive care unit.