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Open research questions in Erythropoietin and Anemia Treatment

113 gap statements mined from Erythropoietin and Anemia Treatment papers in our 4.5M-paper local library, which holds 520 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The study faced challenges in defining ESA hyporesponsiveness due to the lack of a universally accepted absolute ERI threshold. The study had to exclude patients with iron deficiency and those receiving vitamin D supplements to reduce confounding effects.

    Association of Serum 1,25-Dihydroxyvitamin D Levels with Erythropoietin Resistance Index-Based Relative Erythropoiesis-Stimulating Agent Hyporesponsiveness in Pre-Dialysis Chronic Kidney Disease · 2026 · DOI

  • The authors highlight the need for a deeper understanding of the complex relationships between erythropoietin, tumor cells, and immune cells. The paper notes that prior work has been limited by nonspecific antibodies, low receptor abundance, and failure to distinguish between erythropoietin receptor transcripts and intracellular proteins.

    Erythropoietin in Tumor Immunity: Mechanistic Evidence, Clinical Cautions, and Translational Opportunities · 2026 · DOI

  • The study identifies the need for a comprehensive evaluation of long-acting ESAs in the Chinese healthcare context. It also notes the lack of data on the use of darbepoetin alfa in patients with hepatic impairment. The study highlights the importance of considering the Chinese healthcare context in the evaluation of long-acting ESAs.

    Health technology assessment of long-acting erythropoiesis-stimulating agents for the treatment of renal anemia in China · 2026 · DOI

  • The study did not include data on the use of darbepoetin alfa in patients with hepatic impairment. The clinical significance of mild hepatic impairment on the use of pegmolesatide remains unclear.

    Health technology assessment of long-acting erythropoiesis-stimulating agents for the treatment of renal anemia in China · 2026 · DOI

  • There is limited evidence for the use of HIF-PH inhibitors, including daprodustat, in the immediate post-transplant period. The long-term effects of daprodustat on transplant outcomes are unknown.

    The Safety and Efficacy of Daprodustat for Recipients in Peritransplant Period: a Single-Center Retrospective Study on Post-Transplant Anemia Management in Kidney Transplantation · 2025 · DOI

  • The lack of effective treatments for patients with secondary amyloidosis due to Crohn's disease on hemodialysis. The need for alternative treatments for iron deficiency anemia in these patients.

    Patient with Secondary Amyloidosis Due to Crohn’s Disease on Hemodialysis Effectively Treated with Ferric Carboxymaltose Injections: A Case Report and Literature Review · 2025 · DOI

  • However, it remains unclear whether persistent anemia despite erythropoiesis-stimulating agent (ESA) therapy is associated with long-term graft dysfunction in routine clinical practice.

    Post-transplant anemia as a persistent risk factor for graft dysfunction in kidney transplant recipients · 2026 · DOI

  • Patients requiring EPO remained dependent on supplementation, and the long-term impact of sustained EPO use on belzutifan efficacy remains unknown.

    47 Hemoglobin Drop is an Early Predictor of Erythropoietin Supplementation in VHL Syndrome Patients Under Belzutifan Treatment - First Report From The Real-Life BELIEVE-VHL Trial · 2026 · DOI

  • Iron availability and inflammation are important factors in anemia management in hemodialysis patients; however, their longitudinal relationships with erythropoiesis resistance index (ERI), including potential temporal effects, remain incompletely understood.

    Inflammation and iron availability in erythropoiesis resistance: a longitudinal patient-month analysis in hemodialysis patients · 2026 · DOI

  • Whether the increase in RBCV results from reduced CVP associated with HUS remains unclear and warrants further investigation.

    Did You Know: Erythropoiesis Is Regulated by Changes in Posture · 2026 · DOI

  • The mechanism remains unclear, but in addition to its importance in erythropoiesis, iron availability influences the hypoxia-inducible factor (HIF) transcriptional pathway and modulates physiological responses to hypoxia, particularly within the pulmonary circulation.

    Intravenous iron for the treatment of iron deficiency in adults with cystic fibrosis: a prospective observational cohort study · 2025 · DOI

  • However, some studies suggest a potential link between HIF-PHIs and increased thrombosis risk, though these findings are inconsistent and lack large-scale clinical support.

    HIF-PHIs associated with embolic and thrombotic events: a real-world pharmacovigilance study based on the Japan Adverse Drug Event Report database · 2025 · DOI

  • However, comprehensive bibliometric analyses evaluating global trends, knowledge gaps, and emerging research hotspots in this field remain lacking.

    Global research trends in renal anemia: a multidimensional bibliometric study · 2025 · DOI

  • However, some individuals exhibit ESA resistance, and its underlying mechanisms remain unclear.

    Low sirtuin-1 levels are linked to erythropoietin resistance in hemodialysis patients · 2025 · DOI

  • However, its efficacy and safety in treating anaemia in patients with both CKD and HF remain unclear.

    Efficacy and safety of roxadustat for treating anaemia in patients with chronic kidney disease and heart failure: a retrospective cohort study · 2025 · DOI

  • It fills an important gap in the literature and may inform clinical decision-making and future prospective studies.

    The Safety and Efficacy of Daprodustat for Recipients in Peritransplant Period: a Single-Center Retrospective Study on Post-Transplant Anemia Management in Kidney Transplantation · 2025 · DOI

  • However, analysis of its prevalence, years lived with disability (YLDs) and trends in the population on a global scale is lacking.

    Global, regional, and national burden of renal anemia, 1990 to 2019 and prediction to 2050 · 2025 · DOI

  • Furthermore, little is known regarding the prevalence, pathophysiology, and treatment of iron deficiency and anemia in pregnant women with CKD.

    Anemia in Pregnancy With CKD · 2024 · DOI

  • However, there is no consensus regarding its optimal range for patient with chronic kidney disease (CKD).

    The association between transferrin saturation and all-cause mortality in chronic kidney disease: findings from Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease · 2024 · DOI

  • Moreover, little is known about the magnitude of the effect in advanced CKD, the patient population usually prescribed ESAs or HIF-PH inhibitors.

    Cardio-renoprotective effects of SGLT2 inhibitors—the role of anaemia correction · 2024 · DOI

  • The standard approach to anaemia in non-dialysis chronic kidney disease (CKD) does not account for potential age- or sex-specific related risks.

    A longitudinal analysis of haemoglobin levels and major cardiovascular events · 2025 · DOI

  • Despite their possible influence on the HIF system, this has not been described with SGLT2i so far.

    Cardio-renoprotective effects of SGLT2 inhibitors—the role of anaemia correction · 2024 · DOI

  • The absence of a non-treated control group precludes causal inference regarding the hematologic effects of SGLT2i therapy, - The study had a limited sample size of 118 patients, - The study only included patients with CKD stages…

    Effects of Sodium–Glucose Cotransporter-2 Inhibitors on Anemia in Patients with Chronic Kidney Disease: A Pre–Post Observational Analysis · 2026 · DOI

  • Further studies with a non-treated control group are needed to determine the causal effects of SGLT2i therapy on anemia, - Research on the effects of SGLT2i therapy on anemia in patients with CKD stage 5, - Studies investigating the mechanisms by which SGLT2i therapy affects anemia in patients…

    Effects of Sodium–Glucose Cotransporter-2 Inhibitors on Anemia in Patients with Chronic Kidney Disease: A Pre–Post Observational Analysis · 2026 · DOI

  • Thrombotic risk associated with the use of roxadustat - Potential pro-angiogenic effects of roxadustat - Limited understanding of the long-term safety of roxadustat in kidney transplant…

    Roxadustat for the Treatment of Early Post-Transplantation Anemia · 2025 · DOI

Most-cited papers in Erythropoietin and Anemia Treatment

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Open questions raised by papers listed on this page include: (1) The study faced challenges in defining ESA hyporesponsiveness due to the lack of a universally accepted absolute ERI threshold (“Association of Serum 1,25-Dihydroxyvitamin D Levels with Erythropoietin…”, 2026); (2) It also notes the lack of data on the use of darbepoetin alfa in patients with hepatic impairment (“Health technology assessment of long-acting erythropoiesis-stimulating agents…”, 2026); (3) It remains unclear whether persistent anemia despite erythropoiesis-stimulating agent (ESA) therapy is associated with long-term graft dysfunction in routine clinical practice (“Post-transplant anemia as a persistent risk factor for graft dysfunction in…”, 2026); (4) Patients requiring EPO remained dependent on supplementation, and the long-term impact of sustained EPO use on belzutifan efficacy remains unknown (“47 Hemoglobin Drop is an Early Predictor of Erythropoietin Supplementation in…”, 2026); (5) Whether the increase in RBCV results from reduced CVP associated with HUS remains unclear and warrants further investigation (“Did You Know: Erythropoiesis Is Regulated by Changes in Posture”, 2026). 113 gap statements have been mined from Erythropoietin and Anemia Treatment papers in our 4.5M-paper local library, which holds 520 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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