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

Abstract

<b><i>Background:</i></b> We tested the effect of uremia on red blood cell (RBC) eryptosis, CD14<sup>++</sup>/CD16<sup>+</sup> monocytes and erythrophagocytosis. <b><i>Design:</i></b> 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. <b><i>Results:</i></b> 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<sup>++</sup>/CD16<sup>+</sup> 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<sup>++</sup>/CD16<sup>+</sup> (60.8 ± 10%) than in CD14<sup>++</sup>/CD16<sup>-</sup> (15.5 ± 2%). <b><i>Conclusions:</i></b> 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.