Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

Abstract

Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10–11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

The Influence of Inflammation on Anemia in CKD Patients

“…Sotatercept is a fusion protein comprising of an extracellular chain of activin receptor IIA and the Fc domain of human IgG1. It inhibits the activation of endogenic, membranous receptors (ActRIIA) of activin by binding circulating activin and related proteins (e.g., BMP 10 and BMP 11) [104] Moreover, it influences the expression of angiotensin II which can promote erythropoiesis directly and indirectly via EPO production [105]. Sotatercept also stimulates the release of the mature erythrocyte forms, decreases the expression of the vascular endothelial growth factor (VEGF), which is an inhibitor of erythropoiesis and inhibits hepcidin transcription in the liver [106].…”

In vitro modifying effect of erythropoietin upon thymic lymphocytes: an inhibitor analysis

“…Th erefore, recombinant erythropoietins-alpha (Eprex, Epobioicrine, Epostim etc.) are widely used to correct anemias in diff erent diseases and posttransplant conditions [2].…”

Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelial-to-mesenchymal transition and ameliorate renal interstitial fibrosis

“…EPO is the major growth factor involved in erythropoiesis and has been used to treat renal anemia in patients with advanced CKD in clinical practice [41]. Studies have demonstrated that EPO has cytoprotective effects in many non-erythroid cells, including renal TECs, which are largely attributed to anti-apoptosis, anti-oxidant, and anti-in ammatory effects [42].…”