Anemia is a common complication of chronic kidney disease (CKD). Despite an increase in attention to the prevalence of renal anemia, there remains a large population of patients with CKD who do not meet hemoglobin (Hb) targets. Novel therapeutic agents for renal anemia have emerged with the discovery of prolyl hydroxylase domain (PHD) enzymes to regulate hypoxia-inducible factor (HIF)-dependent erythropoiesis. Phase 3 trials have been completed for roxadustat, the first small-molecule HIF-PHD inhibitor. Worldwide, there are more than 15 phase 3 clinical trials examining the efficacy and safety of roxadustat in CKD patients with anemia.
Zuo-Lin Li, MD, and colleagues at the Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China, conducted a review to summarize recent findings regarding the use of roxadustat to treat renal anemia. The review was published in Kidney Diseases [2020;6; 65-73].
The use of erythropoiesis-stimulating agents (ESAs) and iron supplementation is well established and effective in treating renal anemia; however, those therapies are associated with safety concerns. Findings to date from the phase 2 and phase 3 trials of roxadustat suggest that the agent is clinically effective and well tolerated.
The findings demonstrate that by inducing HIF pathway activation transiently, roxadustat could increase levels of endogenous erythropoietin (EPO) to within or a near physiologic range in a titratable manner. Further, by decreasing serum hepcidin and increasing intestinal iron absorption, roxadustat improves iron metabolism, which is beneficial to functional iron deficiency as well as absolute iron deficiency. In addition, the erythropoietic response of roxadustat is independent of the baseline inflammatory state of CKD patients.
In summary, the authors said, “Roxadustat is an emerging and promising therapeutic approach against anemia in CKD patients, which differs from those of conventional ESAs. Roxadustat corrects anemia of CKD patients through multiple pathways, beyond elevating EPO levels within physiological range, and also by handling iron metabolism (particularly decreasing the hepcidin levels). Furthermore, the Hb response of roxadustat is independent of the inflammatory microenvironment.”