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To facilitate timely diagnosis and rapid treatment initiation for anemia in CKD, the multidisciplinary and interprofessional CKD-anemia treatment team should be aware of the significant impact of anemia on patient quality of life, progression of CKD, and cardiovascular events. Erythropoietin-stimulating agents (ESAs) are associated with significant cardiovascular safety-related concerns, but the emergence of the oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) may improve erythropoiesis without the undesirable downstream effects of ESAs. However, HIF-PHIs place in therapy has not yet been fully elucidated. Here, join the interprofessional team of Dr. Ajay Singh, Dr. Jane Davis, and Dr. Calvin Meaney as they explore an incisive review of current CKD-anemia treatment and diagnostic challenges, as well as the evidentiary base for HIF-PHI utilization in CKD-anemia that establishes context for the future of these agents. In conclusion, a practical discussion of real-world patient case scenarios will be presented, to provide learners with context of the multiple comorbidities, complexities, diagnostic challenges, and barriers to appropriate treatment of CKD-anemia.