Erythropoiesis-Stimulating Agents (ESAs) in Chronic Kidney Disease and Cancer-Related Anemia: A Narrative Review of Literature

Abstract

Anemia associated with chronic kidney disease (CKD) and cancer is conventionally managed with packed red blood cell (PRBC) transfusions or erythropoietin-stimulating agents (ESAs) like epoetin alfa; however, transfusions are limited by complications such as alloimmunization and infection risk, which has led to ESAs becoming the preferred standard of care. Additional therapy may include iron supplementation, which potentially causes complications such as iron overload and infection risks in respective patient populations. The introduction of recombinant human erythropoietin (rhEPO) in 1989 improved anemia management but also raised concerns about adverse cardiovascular outcomes in many studies. Current guidelines promote careful ESA use to balance benefits and risks, while alternatives like hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) show promise in reducing such adverse effects. This review explores ESA trends, challenges, and emerging therapies for anemia in CKD and cancer patients and their implications in clinical use.

The literature search for this narrative review was conducted on PubMed in January 2025. The search was restricted to articles published between January 2020 and January 2025, focusing on randomized controlled trials (RCTs), narrative reviews, systematic reviews, and meta-analyses. The initial PubMed search yielded 454 articles, which were subsequently screened according to the inclusion and exclusion criteria, resulting in a final selection of 58 publications that satisfied the eligibility requirements.

Overall, evidence from these studies suggests that ESAs are considerably beneficial in correcting anemia and lowering the need for blood transfusions in adult patients with CKD. However, concerns about adverse cardiovascular outcomes and their effects on optimal hemoglobin targets have indicated the need to shift treatment approaches. These articles have also suggested recent developments, including the advent of HIF-PHIs and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which have been shown to offer safer and therapeutically promising alternatives in anemia of CKD and cancer-related anemia. Tailored approaches that take patient-specific factors into account are necessary for optimizing outcomes, suggesting that further research is required to evaluate the efficacy and risks of these novel treatments within clinical settings.

The narrative review has summarized the benefits and drawbacks of ESAs as a widely used treatment for anemia of CKD and cancer-related anemia. Studies identified in this review have shown that ESAs are linked to increased risks of adverse cardiovascular events, tumor progression in cancers, and higher mortality rates. The emerging alternative of HIF-PHIs shows promise in mitigating these adverse risks with a similar treatment efficacy to ESAs. However, there is still a lack of long-term safety data on these treatment options, and future research should focus on determining this risk profile as well as potential dosing strategies to potentially guide the use of HIF-PHIs in future clinical practice as a novel therapeutic alternative for anemia of CKD and cancer-related anemia.