<p>Erythropoietin Resistance in Patients with Chronic Kidney Disease: Current Perspectives</p>

Abstract

Anemia is a frequent complication of chronic kidney disease, and its primary cause is erythropoietin deficiency. After diagnosis, treatment begins with administration of an erythropoiesis-stimulating agent (ESA). However, some patients present with resistance to ESA, which needs to be reversed, as it can increase the risk of death in patients with kidney disease. Therefore, we provide a discussion of the current literature regarding the factors that can modify the response to this class of drugs and the strategies that can be considered to optimize the benefits of treating anemia.

Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state

“…Chronic kidney disease is caused by multitude of factors including erythropoietin (EPO) deficiency, abnormal iron metabolism, hemolysis, chronic inflammation, reduced erythrocyte survival duration, infection, oxidative stress, and nutritional deficits ( Babitt and Lin, 2012 ). A severe form of CKD decreases the quality of life and increases the risk of cardiovascular diseases and mortality ( Santos et al., 2020 ). Erythropoiesis-stimulating agents (ESA) such as epoetin alfa or beta, biosimilars, and longer-acting agents ESAs are generally used to treat anemia associated with CKD ( Hayat et al., 2008 ).…”

“…Hyporesponsiveness to ESA or EPO resistance occurs in a substantial population of CKD patients, when the patient cannot reach normal hemoglobin (Hb) levels using a recommended dose of ESA ( Sibbel et al., 2015 ). In EPO-resistant patients, a continuing EPO treatment increases the risk of death due to increased blood pressure, increased blood viscosity, and deranges platelet function ( Santos et al., 2020 ). Thus, improving EPO resistance in patients with CKD is vital for improving anemia and also for reducing morbidity and mortality.…”

“…Erythropoiesis stimulatory agents (ESA), such as recombinant human erythropoietin (rhEPO), substantially benefit patients with CKD ( Hayat et al., 2008 ). However, ESA treatment is associated with adverse cardiovascular events, and many CKD patients exhibit a poor hematologic response to ESA, mainly due to inadequate iron supply to the erythron ( Santos et al., 2020 ). Other causes of ESA resistance include infection, neoplasia, severe hyperparathyroidism, aluminum intoxication, vitamin B12 deficiency, inadequate dialysis, myelosuppressive agents, and antibody-mediated pure red cell aplasia ( Santos et al., 2020 ; Ganz and Nemeth, 2016 ).…”

“…However, ESA treatment is associated with adverse cardiovascular events, and many CKD patients exhibit a poor hematologic response to ESA, mainly due to inadequate iron supply to the erythron ( Santos et al., 2020 ). Other causes of ESA resistance include infection, neoplasia, severe hyperparathyroidism, aluminum intoxication, vitamin B12 deficiency, inadequate dialysis, myelosuppressive agents, and antibody-mediated pure red cell aplasia ( Santos et al., 2020 ; Ganz and Nemeth, 2016 ). There is significant variability and loss of sensitivity in the patient response to rhEPO, and this resistance to rhEPO therapy can increase the mortality and morbidity in CKD patients ( Fukuma et al., 2012 ).…”

Comparison of Packed Cell Volume Changes after Erythropoietin Administration and Blood Transfusion in Patients with Anemia of Chronic Kidney Disease on Hemodialysis

“…Variation in hematological parameters in CKD 5 HD patients undergoing these therapies is related to adjustments in ESA therapy or blood transfusion, variation in hydration status, inflammatory processes, correction of iron deficiency, blood loss such as due to access surgery and dialysis adequacy. 3 This study aimed to compare the changes in PCV between patients on ESA therapy and blood transfusion at the start, four weeks, eight weeks, and twelve weeks of therapies.…”