Uremic Toxicity-Induced Eryptosis and Monocyte Modulation: The Erythrophagocytosis as a Novel Pathway to Renal Anemia

Background: We tested the effect of uremia on red blood cell (RBC) eryptosis, CD14(++)/CD16(+) monocytes and erythrophagocytosis. Design: RBC and monocytes from chronic kidney disease (CKD) stages 3/4 (P-CKD3/4) or hemodialysis (HD) patients and healthy controls (HCs) cells incubated with sera pools from patients with CKD stages 2/3 (S-CKD2/3) or 4/5 (S-CKD4/5) were evaluated to assess eryptosis, monocyte phenotypes and reactive oxygen species (ROS) by cytometer. Erythrophagocytosis was evaluated by subsequent co-incubation of preincubated HC-monocytes and autologous-RBC. Results: HC-eryptosis (1.3 +/- 0.9%) was lower than in HD (4.3 +/- 0.5%) and HC-RBC incubated with S-CKD4/5 (5.6 +/- 1%). CD14(++)/CD16(+) were augmented in P-CKD3/4 (34.6 +/- 8%) and HC-monocytes incubated with S-CKD4/5 (26.4 +/- 7%) than in HC (5.4 +/- 1%). In these cells, ROS was increased (44.5 +/- 9%; control 9.6 +/- 2%) and inhibited by N-acetylcysteine (25 +/- 13%). Erythrophagocytosis was increased in CD14(++)/CD16(+) (60.8 +/- 10%) than in CD14(++)/CD16(+) (15.5 +/- 2%). Conclusions: Sera pools from CKD patients increase eryptosis and promote a proinflammatory monocyte phenotype. Both processes increased erythrophagocytosis, thereby suggesting a novel pathway for renal anemia. (C) 2016 S. Karger AG, Basel