What Should Be Responsible for Eryptosis in Chronic Kidney Disease?

Abstract

Background: Renal anemia is an important complication of chronic kidney disease (CKD). In addition to insufficient secretion of erythropoietin (EPO) and erythropoiesis disorders, the impact of eryptosis on renal anemia demands attention. However, a systemic analysis concerning the pathophysiology of eryptosis has not been expounded. Summary: The complicated conditions in CKD patients, including oxidative stress, osmotic stress, metabolic stress, accumulation of uremic toxins, and iron deficiency, affects the normal skeleton structure of red blood cells (RBCs) and disturbs ionic homeostasis, causing phosphatidylserine to translocate to the outer lobules of the RBC membrane that leads to early elimination and/or shortening of the red blood cell lifespan (RBCL). Inadequate synthesis of RBCs cannot compensate for their accelerated destruction, thus exacerbating renal anemia. Meanwhile, EPO treatment alone will not reverse renal anemia. A variety of eryptosis inhibitors have so far been found, but evidence of their effectiveness in the treatment of CKD remains to be established. Key Messages: In this review, the pathophysiological processes and factors influencing eryptosis in CKD were elucidated. The aim of this review is to underline the importance of eryptosis in renal anemia and determine some promising research directions or possible therapeutic targets to correct anemia in CKD.

Molecular Mechanisms and Pathophysiological Significance of Eryptosis

“…Patients in the later stages of chronic renal impairment (stages G4 and G5) have greater eryptosis levels than those in the earlier stages of the illness (stage G1, G2 and G3) [ 99 ]. Erythrocytosis in chronic renal illness can be affected by a number of factors [ 100 ], including oxidative stress, energy loss, and uremic toxins. All these factors contribute to an increased rate of RBC mortality, and they all rise alongside a decline in renal function.…”

“…Reactive oxygen species (ROS) cause damage to the lipids and proteins of RBC membranes, which in turn causes reorganization of the erythrocyte skeleton and a decrease in the membrane’s stability and deformability [ 104 ]. Finally, oxidative stress promotes microvesicle activity and caspase activation, both of which exacerbate eryptosis and renal anemia [ 100 ].…”

Eryptosis in Patients with Chronic Kidney Disease: A Possible Relationship with Oxidative Stress and Inflammatory Markers

“…Indeed, different factors influence eryptosis levels in chronic kidney disease, such as oxidative stress, energy depletion, and uremic toxins [ 11 ]. All of them increase with the progressive impairment of kidney function, thus stimulating RBCs’ death levels.…”

“…ROS induce an injury to the lipids and proteins of RBC membranes, thus resulting in the rearrangement of the erythrocyte skeleton and the reduction of cell membrane stability and deformability [ 24 ]. Moreover, oxidative stress induces the activity of microvescicles and activates caspases, all of which aggravate eryptosis that eventually leads to renal anemia [ 11 ].…”

“…End-stage renal disease is also characterized by a suppression of the antioxidant system which exacerbates oxidative stress. All these factors are responsible for the impairment of RBC membrane structures in patients with CKD [ 11 , 12 ].…”