The clinical outcomes of acute kidney injury substages based on serum cystatin C in pediatric patients undergoing cardiac surgery

Background Multiple biomarkers have been identified by previous studies to diagnose acute kidney injury (AKI). Moreover, combination of biomarkers with conventional criteria to define AKI substages so that we can identify high-risk patients and improve diagnostic accuracy were recommended. Our study aimed to explore the incidence of AKI substages defined by serum cystatin C (CysC), determine whether AKI substages were associated with worse outcomes. Methods We prospectively included 2519 pediatric patients (<16yrs) undergoing cardiac surgery with cardiopulmonary bypass in our cohort between March 2022 to February 2023 in Fuwai Hospital. Demographic and clinical variables we collected. To define AKI substages, Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC) was used. The association between AKI exposure and outcomes including length of intensive care unit stay, duration of mechanical ventilation, length of hospital stay and 30-day mortality was assessed. In addition, we determined areas under the receiver operating characteristic curve and cutoff value of CysC at different timepoints to predict AKI. Results 507 (20.8%) patients developed SCr-AKI, with 337 (13.8%) in stage 1, 77(3.2%) in stage 2 and 93 (3.8%) in stage 3 respectively. Of the 1925 patients without SCr-AKI, 256 (14.3%) met the definition of sub-AKI. Of the 507 patients with SCr-AKI, 281 (55.4%) patients were defined as AKI substage A, while others (226, 44.6%) were defined as AKI substage B. After adjusting for BSA, neonates, STAT mortality score≥4, previous sternotomy and CPB time>120min, the postoperative LOIS, LOHS and DMV were prolonged with increasing hospitalization expense (P<0.05) in patients with SCr-AKI and/or CysC-AKI. Meanwhile, only the hospitalization expense was increased in patients with SCr-AKI(P<0.05) after the same adjustment. The AUC was 0.691, 0.720 and 0.817 respectively in ROC curves of preoperative, relative variation of or postoperative serum CysC. Delong’ test showed that postoperative serum CysC might have better diagnostic performance characteristic than preoperative or relative variation of CysC (P<0.001), with a cutoff point at 1.29 mg/dL (Specificity, 0.77; Sensitivity, 0.71) Conclusions Our analysis indicates defining AKI with both CysC and SCr might more significantly affecting clinical outcome associations in pediatric patients undergoing cardiac surgery. Moreover, the serum CysC cutoff of 1.29mg/dL postoperatively is a valuable threshold for AKI risk assessment to define AKI subtypes. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The study was registered at ClinicalTrials (https://clinicaltrials.gov/) ([NCT05489263][1], A predictive Score System for AKI Following Pediatric Cardiac Surgery). ### Funding Statement This study was supported by Chinese Academy of Medical Sciences Central Public Welfare Scientific Research Institute Basal Research Expenses?Clinical and Translational Medicine Research Fund [2021-I2M-C&T-B-036]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethical Committee of Fuwai Hospital (Approval No. 2021-1607) . I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable The data that support the findings of this study are available from the corresponding author upon reasonable request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05489263&atom=%2Fmedrxiv%2Fearly%2F2023%2F05%2F04%2F2023.04.25.23289121.atom