Burden of Anemia in Chronic Kidney Disease: Beyond Erythropoietin

Abstract

Anemia is a frequent comorbidity of chronic kidney disease (CKD) and is associated with a considerable burden because of decreased patient health-related quality of life and increased healthcare resource utilization. Based on observational data, anemia is associated with an increased risk of CKD progression, cardiovascular events, and all-cause mortality. The current standard of care includes oral or intravenous iron supplementation, erythropoiesis-stimulating agents, and red blood cell transfusion. However, each of these therapies has its own set of population-specific patient concerns, including increased risk of cardiovascular disease, thrombosis, and mortality. Patients receiving dialysis or those who have concurrent diabetes or high blood pressure may be at greater risk of developing these complications. In particular, treatment with high doses of erythropoiesis-stimulating agents has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Resistance to erythropoiesis-stimulating agents remains a therapeutic challenge in a subset of patients. Hypoxia-inducible factor transcription factors, which regulate several genes involved in erythropoiesis and iron metabolism, can be stabilized by a new class of drugs that act as inhibitors of hypoxia-inducible factor prolyl-hydroxylase enzymes to promote erythropoiesis and elevate hemoglobin levels. Here, we review the burden of anemia of chronic kidney disease, the shortcomings of current standard of care, and the potential practical advantages of hypoxia-inducible factor prolyl-hydroxylase inhibitors in the treatment of patients with anemia of CKD.

Clinical Implications of the Coexistence of Anemia and Diabetes Mellitus in the Elderly Population

“…Vitamin B12 and folate deficiency is frequently observed among diabetic patients [ 15 , 40 ]. Erythropoietin (EPO) deficiency and/or resistance, iron deficiencies (resulting from reduced dietary intake, impaired enteral absorption, blood loss), and proteinuria (with loss of transferrin or EPO) are mechanisms leading to anemia development in patients with diabetic kidney disease [ 41 , 42 ]. In men with type 2 DM, obesity, and insulin resistance, low testosterone levels are often found, which may also increase the risk of anemia [ 43 ].…”

“…Anemia leads to hypoxia and the impairment of many tissues and organs, especially the circulatory and renal. Poorer cardiovascular and renal functions, in turn, are factors contributing to anemia [ 41 , 42 , 57 ]. This results in a “vicious cycle” and seems to be an important factor in the coexistence of anemia and diabetes.…”

Current Status of Renal Anemia Pharmacotherapy—What Can We Offer Today

“…The prevalence of renal anemia gradually rises as the estimated glomerular filtration rate (eGFR) decreases [ 3 ]. Anemia occurs in approximately half of patients with CKD stage G4 and in more than 90% of the end-stage renal disease patients who undergo dialysis [ 3 , 4 , 5 ]. Correcting renal anemia can decrease mortality, hospitalization, risk of CKD progression, and improve the health-related quality of life [ 5 , 6 , 7 , 8 , 9 , 10 ].…”

Anemia in Chronic Kidney Disease : Role of Hypoxia Inducible Factor Stabilizer

“…3 The current standard of care for anemia in CKD includes erythropoiesis-stimulating agents (ESAs), suplemental iron, and red blood cell (RBC) transfusion, each of which has potential problems and variable effectiveness. [4][5][6] Available ESAs are very effective drugs, usually obtaining significant hemoglobin (Hb) level increases. proteins.…”