Title : Novel anaemia therapy in chronic kidney disease: Expectations and myths of adverse drug reactions
Abstract:
Background: Renal anaemia remains a pervasive challenge among individuals with chronic kidney disease (CKD), often being underdiagnosed and inadequately treated. The advent of hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) has introduced new therapeutic possibilities, offering an alternative to traditional erythropoiesis-stimulating agents. Despite their potential, the adverse drug reactions (ADRs) associated with HIF-PHIs are not fully understood, leaving gaps in knowledge that could impact patient safety. This review seeks to identify and thoroughly analyse ADRs to HIF-PHIs, with a focus on understanding their variability, severity, preventability, and overall outcomes in CKD patients, as reported in individual case studies and reports.
Methods: A systematic literature search was conducted across multiple electronic databases, covering case reports published between January 2018 and June 2024. The search aimed to capture a comprehensive range of ADRs linked to HIF-PHIs in CKD anaemia. From an initial pool of 2,123 studies, only 8 case reports and/or studies, encompassing 13 patients, met the stringent inclusion and exclusion criteria required for this review.
Results: The review identified ADRs associated with two HIF-PHIs: roxadustat (62%) and daprodustat (39%). Reported ADRs included retinal haemorrhage (7.7%), hypertension (15.4%), stroke (23.1%), hypothyroidism (7.7%), rhabdomyolysis (7.7%), and elevated serum copper levels (38.4%). The mean time-to-onset of these ADRs was 6.5 months, indicating a need for prolonged monitoring in patients receiving HIF-PHIs. Specific causality and non-preventability of ADRs were confirmed in one report (12.5%), while two reports (25%) highlighted a definite probability and severity of ADRs directly attributable to HIF-PHIs.
Conclusion: This review underscores the importance of vigilant monitoring and personalised treatment strategies when using HIF-PHIs to manage CKD anaemia. While HIF-PHIs show promise in treating this condition, the identified ADRs highlight the need for careful patient selection, dosing adjustments, and management of underlying comorbidities to mitigate risks. By maintaining recommended haemoglobin levels and addressing potential ADRs proactively, healthcare providers can optimise the safety and effectiveness of HIF-PHIs in chronic disease management. This review calls for further research to expand our understanding of ADRs in diverse patient populations, ensuring that HIF-PHIs can be safely integrated into broader CKD treatment protocols.
