Eryptosis: a driver of anemia in chronic kidney disease

Abstract

Purpose of review Anemia, characterized by a reduction in red blood cell (RBC) count or hemoglobin concentration, commonly accompanies chronic kidney disease (CKD), significantly impacting patients’ quality of life. This review delves into the multifaceted nature of anemia in CKD, with a focus on novel mechanisms, particularly the dysregulation of eryptosis or programmed cell death of RBCs, leading to shortened RBC lifespan. Recent findings Recent studies in CKD patients and mouse models revealed that eryptosis, driven by factors such as uremic toxins, inflammation, and imbalances in calcium homeostasis, plays a pivotal role in the development of renal anemia. Dysregulated eryptosis results in premature RBC destruction, exacerbating the hypoproliferative character of anemia in CKD. Summary Recognizing the intricate relationship between eryptosis and anemia in CKD opens promising prospects for improving patient outcomes and enhancing our understanding of this complex condition. Future research and therapeutic development in this area hold the potential to improve anemia treatment of CKD patients.

Toward a Mechanism-Driven Integrated Framework to Link Human Exposure to Multiple Toxic Metal(loid) Species with Environmental Diseases

“…The observation of an Hb–Hg complex in the kidneys of rats exposed to Hg 2+ is of immediate toxicological relevance as free Hb is known to cause kidney damage [ 116 ]. Interestingly, chronic kidney disease (CKD), the etiology of which is still unknown, has been demonstrated to induce RBC death, which is referred to as ‘eryptosis’ [ 117 ], further underscoring the importance of an integrated approach to establish the biomolecular mechanism of chronic toxicity of potentially toxic metal(loid) species in the bloodstream–organ system.…”

Anemia of Chronic Kidney Disease—A Narrative Review of Its Pathophysiology, Diagnosis, and Management

“…Yet, one key advantage of long-acting ESAs is their longer half-life, allowing for less frequent administration compared to short-acting ESAs like epoetin alfa and epoetin beta. This less frequent dosing regimen simplifies the work for healthcare providers in hemodialysis centers and contributes to better hemoglobin stability [ 120 ]. Interestingly, the efficacy of ESAs seems to not be affected by the type of ESA or the dosing interval, as observed in patients receiving chronic peritoneal dialysis [ 121 ].…”

“…Firstly, the association between lower calcium levels and high phosphorus concentrations and anemia in CKD patients has been determined, yet the clinical significance remains uncertain, highlighting the need for further investigation into these associations [ 155 ]. Secondly, the role of eryptosis, or programmed cell death of red blood cells, in contributing to anemia in CKD patients is still uncertain, necessitating a deeper understanding of this mechanism and its implications for anemia management [ 120 ]. Lastly, there are the challenges in addressing anemia in frail elderly patients with CKD and multiple comorbidities, hospitalized patients, and kidney transplant recipients who may have reduced response to iron and ESA therapy [ 156 ].…”