Red blood cell abnormalities and the pathogenesis of anemia in end‐stage renal disease

Abstract

Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in ESRD is controversial due to the "anemia paradox" phenomenon, which underlines the need for a more individualized approach to therapy. RBCs imprint the adverse effects of uremic, inflammatory, and oxidative stresses in a context of structural and functional deterioration that is associated with RBC removal signaling and morbidity risk. RBCs circulate in hostile plasma by raising elegant homeostatic defenses. Variability in primary defect, co-morbidity, and therapeutic approaches add complexity to the pathophysiological background of the anemic ESRD patient. Several blood components have been suggested as biomarkers of anemia-related morbidity and mortality risk in ESRD. However, a holistic view of blood cell and plasma modifications through integrated omics approaches and high-throughput studies might assist the development of new diagnostic tests and therapies that will target the underlying pathophysiologic processes of ESRD anemia.

Erythrocyte Alterations and Increased Cardiovascular Risk in Chronic Renal Failure

“…However, one recent preclinical experience suggests that rat RBCs preserved for 2 weeks at 4°C are less effective in ensuring normal oxygenation in the microcirculation than nonpreserved RBCs (17). Now, it is known that blood bankstored RBCs for transfusion are prone to various alterations (18); these involve the RBC membrane-skeleton and rheologic properties to an extent similar to the defects found in uremic patients' RBCs (19). Such alterations might explain not only the above-mentioned experimental observation as to the microcirculation oxygenation, but also some potential hypoxic effects to the coronary microcirculation and attendant CV risk.…”

Clinical characteristics of anemia in chronic kidney disease of patients of the National Hospital in 2018

“…Además, pueden adherirse a la pared vascular y perjudicar la microcirculación. Entre los estimuladores de la eriptosis están el complemento, los estados hiperosmóticos, la falta de calorías, el estrés oxidativo, los xenobióticos, (28,29) las toxinas urémicas, la eritropoyetina y las hemodiálisis .…”

Anemia of Inflammation

“…The presence of renal failure can exacerbate the effects of inflammation. Uremia is associated with reduced levels of albumin, increased levels of nitric oxide, and changes in the levels of erythrocyte membrane proteins that promote the accumulation of reactive oxygen species and oxidation of erythrocyte membrane proteins (reviewed in [50]). These alterations are thought to accelerate erythrocyte destruction and tissue injury.…”