Subclinical and clinical acute kidney injury share similar urinary peptide signatures and prognosis

Purpose Acute kidney injury (AKI) is a frequent and severe condition in intensive care units (ICUs). In 2020, the Acute Dialysis Quality Initiative (ADQI) group proposed a new stage of AKI, referred to as stage 1S, which represents subclinical disease (sAKI) defined as a positive biomarker but no increase in serum creatinine (sCr). This study aimed to determine and compare the urinary peptide signature of sAKI as defined by biomarkers. Methods This is an ancillary analysis of the prospective, observational, multinational FROG-ICU cohort study. AKI was defined according to the Kidney Disease Improving Global Outcome definition (AKI KDIGO ). sAKI was defined based on the levels of the following biomarkers, which exceeded the median value: neutrophil gelatinase-associated lipocalin (pNGAL, uNGAL), cystatin C (pCysC, uCysC), proenkephalin A 119–159 (pPENKID) and liver fatty acid binding protein (uLFABP). Urinary peptidomics analysis was performed using capillary electrophoresis-mass spectrometry. Samples were collected at the time of study inclusion. Results One thousand eight hundred eighty-five patients had all biomarkers measured at inclusion, which included 1154 patients without AKI (non-AKI KDIGO subgroup). The non-AKI KDIGO subgroup consisted of individuals at a median age of 60 years [48, 71], among whom 321 (27.8%) died. The urinary peptide signatures of sAKI, regardless of the biomarkers used for its definition, were similar to the urinary peptide signatures of AKI KDIGO (inflammation, haemolysis, and endothelial dysfunction). These signatures were also associated with 1-year mortality. Conclusion Biomarker-defined sAKI is a common and severe condition observed in patients within intensive care units with a urinary peptide signature that is similar to that of AKI, along with a comparable prognosis. Graphical abstract