Renal anemia: from incurable to curable

Abstract

Renal anemia has been recognized as a characteristic complication of chronic kidney disease. Although many factors are involved in renal anemia, the predominant cause of renal anemia is a relative deficiency in erythropoietin (EPO) production. To date, exogenous recombinant human (rh)EPO has been widely used as a powerful drug for the treatment of patients with renal anemia. Despite its clinical effectiveness, a potential risk for increased mortality has been suggested in patients who receive rhEPO, in addition to the economic burden of rhEPO administration. The induction of endogenous EPO is another therapeutic approach that might have advantages over rhEPO administration. However, the physiological and pathophysiological regulation of EPO are not fully understood, and this lack of understanding has hindered the development of an endogenous EPO inducer. In this review, we will discuss the current treatment for renal anemia and its drawbacks, provide an overview of EPO regulation in healthy and diseased conditions, and propose future directions for therapeutic trials that more directly target the underlying pathophysiology of renal anemia.

Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects

“…Erythropoiesis-stimulating agents (ESAs) are used worldwide to treat anemia due to CKD [2] . However, several large-scale trials reported that treatment with ESAs targeting higher hemoglobin targets has been associated with an increased risk of some major cardiovascular events [3][4][5][6] .…”

Renal risk‐benefit determinants of recombinant human erythropoietin therapy in the remnant kidney rat model – hypertension, anaemia, inflammation and drug dose

“…Indeed, it has been reported that in both CKD patients and animal models of CKD, the serum EPO levels are within the normal range or even increased . It is suggested that the serum EPO levels in CRF rats are, probably, insufficient to overcome renal anaemia . The remnant kidney of the CRF animals maintained some renal capacity to induce EPO synthesis, as showed by renal HIF‐2 α and EPO protein expression; even though, their expression levels were clearly reduced, when compared to the Sham kidneys, as the activation of HIF‐2 α appears to reduce with the progression of CKD .…”

Evaluation and Treatment of Anemia in Chronic Kidney Disease [Kronik Bobrek Hastaliklarinda Aneminin Degerlendirilmesi ve Tedavisi]

“…Diyaliz öncesi kronik böbrek hastalarında dört haftada bir uygulanan CERA tedavisi anemiyi düzeltmiş ve Hb değerlerinin istenen sınırlar içinde kararlı kalmasını sağlamıştır [15,[43][44][45]. ESA tedavisi süresince Hb düzeyleri ayda bir kez, demir durumu tedavinin başlangıcında en az ayda bir kez daha sonra 3 ayda bir değerlendirilmelidir.…”

“…Kronik böbrek hastalarında ise aneminin derecesiyle plazma EPO düzeyleri arasındaki ilişki bozulmuştur. Kreatinin klirensi 40 ml/dak/1.73 m 2 altına düştüğünde ekskretuar böbrek fonksiyonu ile paralel olarak endokrin böbrek fonksiyonunun azalması EPO eksikliği ve anemi ile sonuçlanır [14,15]. Deneysel böbrek hasarı modellerinde EPO üreten hücrelerde fonksiyon bozukluğu ve myofibroblast transformasyonu olduğu gösterilmiştir [16].…”