Early detection of acute kidney injury after congenital heart surgery - using urine proteomics to identify new biomarker candidates: a prospective clinical study

BACKGROUND: Acute kidney injury (AKI) is a frequent complication following congenital heart surgery and is associated with increased morbidity and mortality. Early recognition is crucial, yet standard clinical biomarkers result in delayed detection. Urine, which can be collected non-invasively, offers unique insights into kidney function and systemic responses. METHODS: This prospective clinical study aimed to identify novel urinary biomarkers for the early detection of AKI, using high-accuracy proteome profiling. Patients with congenital heart disease undergoing cardiac surgery at Deutsches Herzzentrum der Charité were included in the study. Urine samples were collected at four timepoints: preoperatively and immediately postoperatively, and then again at six and 24 h post-surgery. Samples were analyzed using high-accuracy mass spectrometry. Linear models were applied to identify proteins associated with AKI. RESULTS: A total of 67 patients with a median age of two years were included, of whom thirteen (19%) developed an AKI. Fifteen potential urinary biomarkers were identified. The most promising early indicators of AKI directly after surgery across all age groups were Chitotriosidase-1 (AUC 0.79; 95% CI:0.64–0.94), Kallikrein-1 (AUC 0.76; 95% CI:0.76–0.89), and Carbonic anhydrase 3 (AUC 0.73; 95% CI:0.6–0.87). CONCLUSIONS: High-accuracy mass spectrometry urine proteome profiling enabled the identification of potential new AKI biomarkers directly after congenital heart surgery. Utilization of the urinary markers Chitotriosidase-1, Kallikrein-1 and Carbonic anhydrase 3 has the potential to enable earlier detection of patients at risk for AKI. Further validation in larger, age-stratified pediatric cohorts is required to confirm the diagnostic utility of the identified urinary biomarker candidates.