The outcome of acute kidney injury substages based on urinary cystatin C in critically ill children.

Background: The concept of acute kidney injury (AKI) substages has been recommended to better phenotype AKI and identify high-risk patient groups and therefore improve the diagnostic accuracy of AKI. However, there remains a gap between the recommendation and the clinical application. The study aimed to explore the incidence of AKI substages based on a sensitive AKI biomarker of urinary cystatin C (uCysC), and to determine whether AKI substages were relevant with respect to outcome in critically ill children.

Results: The multicenter cohort study enrolled 793 children in pediatric intensive care unit (PICU) of four tertiary hospitals in China. Children were classified as non-AKI, sub-AKI and AKI substages A and B according to uCysC level at PICU admission. Sub-AKI was defined by admission uCysC level ≥ 1.26 mg/g uCr in children not meeting the KDIGO criteria of AKI. In children who fulfilled KDIGO criteria, those with uCysC < 1.26 was defined as AKI substage A, and with ≥ 1.26 defined as AKI substage B. The associations of AKI substages with 30-day PICU mortality were assessed. 15.6% (124/793) of patients met the definition of sub-AKI. Of 180 (22.7%) patients with AKI, 90 (50%) had uCysC-positive AKI substage B and were more likely to have classical AKI stage 3, compared to substage A. Compared to non-AKI, sub-AKI and AKI substages A and B were risk factors significantly associated with mortality, and the association of sub-AKI (adjusted hazard ratio HR = 2.42) and AKI substage B (adjusted HR = 2.83) with mortality remained significant after adjustment for confounders. Moreover, AKI substage B had increased risks of death as compared with sub-AKI (HR = 3.10) and AKI substage A (HR = 3.19).

Conclusions: Sub-AKI defined/based on uCysC occurred in 20.2% of patients without AKI and was associated with a risk of death close to patients with AKI substage A. Urinary CysC-positive AKI substage B occurred in 50% of AKI patients and was more likely to have classical AKI stage 3 and was associated with the highest risk of mortality.