Excessive erythrophagocytosis accounts for systemic inflammation in chronic kidney disease

Objective: and design Chronic kidney disease (CKD) is associated with persistent systemic inflammation. Reduced red blood cell (RBC) survival in patients with CKD has been identified for several decades. The purpose of this study is to explore whether excessive erythrophagocytosis exists and contributes to systemic inflammation in CKD. Methods: and subjects A CKD rat model was induced by 5/6 nephrectomy. Erythrophagocytosis was evaluated in vivo and in vitro . RT-qPCR and immunohistochemistry were used to determine the inflammatory effects after erythrophagocytosis. Results: Erythrocyte osmotic fragility and deformability progressively declined, and the percentage of PS-exposing RBCs progressively increased in CKD rats. More of erythrocytes from 5/6Nx rats were phagocytosed by macrophages in comparison to those from control rats in vivo and in vitro . Macrophages phagocytosed CKD erythrocytes exhibited higher mRNA levels of IL-6, CXCL-10, CXCL-11, iNOS, IL-1β, ICAM-1 and MCP-1. The red pulp of rats with CKD exhibited higher levels of p-NFκB, IL-6, iNOS and CXCL-10. ELISA results showed significantly increased plasma levels of both IL-6 and CXCL-10 in patients with long-term hemodialysis compared with those in healthy controls. Conclusions: Our results indicated that excessive erythrophagocytosis might be an important source of systemic inflammation in CKD.