Proteomic signatures of renal recovery from acute kidney injury-a translational study in critically ill postoperative patients

BACKGROUND: Acute kidney injury (AKI) is a common complication in critically ill patients and frequently progresses to persistent renal dysfunction. However, mechanisms underlying renal recovery versus persistent dysfunction remain poorly understood. Plasma proteomic profiling may identify proteins and biological pathways associated with the development of acute kidney disease (AKD) subsequent to AKI.

MATERIAL AND METHODS: We conducted a plasma proteomics study within a prospective, single-centre observational cohort of 205 critically ill adult patients in Germany with moderate AKI (KDIGO stage 2) and predefined risk factors for AKI progression (mechanical ventilation and/or vasopressor therapy). Plasma samples from 195 patients were available for analysis in sufficient quantity. The primary outcome was AKD, defined as persistent AKI (KDIGO stage 2 or 3) or death seven days after AKI diagnosis. High-resolution mass spectrometry quantified protein abundances in non-depleted and immunodepleted plasma samples. Proteins associated with AKD were assigned using biostatistical analyses and selected candidates were validated by enzyme-linked immunosorbent assay (ELISA) in the entire cohort.

RESULTS: Out of 195 patients, 103 developed AKD (52.8%). Proteomic profiling assigned 29 proteins in undepleted plasma and 38 proteins in depleted plasma that were significantly associated with development of AKD. In undepleted plasma, gelsolin and Zinc-alpha-2-glycoprotein were prominent candidates. In depleted plasma, S100A9, a component of the Calprotectin complex, showed the strongest association with AKD development. ELISA validation demonstrated higher plasma concentrations of Calprotectin (S100A8/A9) in patients who progressed from AKI to AKD.

CONCLUSIONS: Unbiased plasma proteomics revealed several proteins associated with development of AKD following moderate AKI in critically ill patients. Elevated Calprotectin (S100A8/A9) levels were independently associated with AKD development in ELISA analyses, suggesting a potential role in AKI chronification. Further studies are warranted to validate these findings and explore their mechanistic and clinical implications.