Acute kidney injury in hospitalized children with sickle cell anemia

Abstract

Background: Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifications to the Kidney Disease: Improving Global Outcomes (KDIGO) definition would influence clinical outcomes of AKI in children with SCA hospitalized with a VOC.

Methods: We prospectively enrolled 185 children from 2 - 18 years of age with SCA (Hemoglobin SS) hospitalized with a VOC at a tertiary hospital in Uganda. Kidney function was assessed on admission, 24-48 h of hospitalization, and day 7 or discharge. Creatinine was measured enzymatically using an isotype-dilution mass spectrometry traceable method. AKI was defined using the original-KDIGO definition as ≥ 1.5-fold change in creatinine within seven days or an absolute change of ≥ 0.3 mg/dl within 48 h. The SCA modified-KDIGO (sKDIGO) definition excluded children with a 1.5-fold change in creatinine from 0.2 mg/dL to 0.3 mg/dL.

Results: Using KDIGO, 90/185 (48.7%) children had AKI with 61/185 (33.0%) AKI cases present on admission, and 29/124 (23.4%) cases of incident AKI. Overall, 23 children with AKI had a 1.5-fold increase in creatinine from 0.2 mg/dL to 0.3 m/dL. Using the sKDIGO-definition, 67/185 (36.2%) children had AKI with 43/185 (23.2%) cases on admission, and 24/142 (16.9%) cases of incident AKI. The sKDIGO definition, but not the original-KDIGO definition, was associated with increased mortality (0.9% vs. 7.5%, p = 0.024). Using logistic regression, AKI risk factors included age (aOR, 1.10, 95% CI 1.10, 1.20), hypovolemia (aOR, 2.98, 95% CI 1.08, 8.23), tender hepatomegaly (aOR, 2.46, 95% CI 1.05, 5.81), and infection (aOR, 2.63, 95% CI 1.19, 5.81) (p < 0.05).

Conclusion: These results demonstrate that AKI is a common complication in children with SCA admitted with VOC. The sKDIGO definition of AKI in children with SCA was a better predictor of clinical outcomes in children. There is need for promotion of targeted interventions to ensure early identification and treatment of AKI in children with SCA.

Keywords: Acute kidney injury; Children; Cystatin C; Hemoglobinuria; Infection; Malaria; Serum creatinine; Sickle cell anemia; Sub-Saharan Africa; Vaso-occlusive crises.

Fig. 1

Flow chart of study population. AKI was defined in children according to the original KDIGO definition or a modified definition (sKDIGO) where children with a 1.5-fold increase in serum creatinine (SCr) from 0.2 to 0.3 mg/dL was not considered AKI. AKI status was defined as admission AKI if a child met criteria for AKI using the admission SCr based on the nadir SCr measured over hospitalization or incident AKI in children whom did not have AKI on admission but developed it over hospitalization. When assessing the incidence of AKI over hospitalization, children with AKI present on admission were excluded from the denominator. *Children with a maximum AKI stage higher than the admission AKI stage were considered to have worsening AKI

Fig. 2

AKI prevalence and stage based on KDIGO or sKDIGO definition. The prevalence of AKI and AKI stage over hospitalization (any AKI), admission, and incident AKI (developed in-hospital). Creatinine was measured on admission, 24–48 h of hospitalization, and discharge or day 7 (whichever happened earlier). For sKDIGO definition children with a 50% increase in creatinine from a baseline measure of 0.2 mg/dL were not considered to have AKI

Fig. 3

Comparison of Cystatin C levels based on the KDIGO AKI definition. A Box and whisker plots showing the median (interquartile range) and range of serum Cystatin C with the individual data points overlaid. Differences between groups were compared using Wilcoxon rank-sum test with the p values presented on the graphs. B Receiver operating characteristic (ROC) curve to measure the association between the biomarker level and AKI status. Serum Cystatin C had a higher area under the receiver operating characteristic (ROC) curve (AUROC) using sKDIGO compared to KDIGO