Role of Inflammatory Cytokine Adsorption on VA-ECMO-Induced Acute Kidney Injury of Rats.

Abstract

Extracorporeal membrane oxygenation (ECMO) is a high-risk, invasive therapy that sustains life through an external system. However, it often leads to complications such as bleeding, thrombosis, infection, and acute kidney injury (AKI). While up to 70% of ECMO patients develop AKI, the mechanisms driving this injury remain unclear, and effective treatments are limited. To address this, we developed a rat model of AKI induced by veno-arterial ECMO (VA-ECMO) and tested the protective effects of a multi-targeted inflammatory factor adsorption technology. Rats undergoing 3-h VA-ECMO exhibited hallmark renal dysfunction, including elevated levels of serum creatinine (Scr) and increased blood urea nitrogen (BUN), accompanied by upregulated renal inflammatory cytokines and tubular apoptosis. Incorporating a cytokine-targeted hemoperfusion device normalized Scr/BUN levels, reduced histopathological damage, and suppressed apoptosis. Mechanistically, adsorption therapy downregulated pro-inflammatory mediators and rebalanced apoptotic regulators, favoring anti-apoptotic Bcl-2 over pro-apoptotic Bax and cleaved caspase-3. These results demonstrate that cytokine adsorption alleviates VA-ECMO-induced AKI through dual suppression of systemic inflammation and intrinsic apoptosis. This study provides a mechanistic basis for clinical translation of adsorption-based strategies to preserve renal function in ECMO patients, addressing a critical unmet need in critical care.