Poor prognosis of acute kidney injury superimposed on chronic kidney disease: potential mechanisms, risk factors and novel biomarkers

Acute kidney injury superimposed on chronic kidney disease (acute-on-chronic kidney injury, hereinafter referred to as AoCKI) is a common clinical syndrome with a generally poor prognosis compared to isolated acute kidney injury (AKI). Patients with AoCKI often face significantly heightened mortality, increased dependence on renal replacement therapy (RRT), and reduced likelihood of renal function recovery. Crucially, the pathophysiological mechanism of AoCKI is not merely an additive effect of two separate conditions, but a distinct synergistic insult driven by pre-existing microvascular and metabolic vulnerabilities. While recent clinical epidemiological studies have enhanced understanding of AoCKI, the mechanisms underlying its poor prognosis remain insufficiently elucidated, and research on population-specific biomarkers is limited. Most currently available biomarkers were identified in patients with isolated AKI and have not been specifically studied in the context of CKD. This review synthesizes previous findings and relevant research to examine the risk factors for AoCKI, as well as the potential pathophysiological mechanisms and biomarkers associated with impaired renal adaptive repair. The objective is to inform the development of more effective preventive measures, diagnostic criteria, and treatment strategies to improve outcomes for this patient population.