Effects of Roxadustat on Thyroid Profiles in Patients and Animals with Chronic Kidney Disease

INTRODUCTION: Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor used in renal anemia treatment, has been associated with thyroid hormone suppression. This study investigated the patterns of thyroid profile changes following roxadustat administration and their clinical implications. METHODS: In this retrospective study (2019-2023) at Shenzhen Second People's Hospital, patients were categorized based on thyroid-stimulating hormone (TSH) reduction during follow-up (≥50% decrease vs. <50% decrease). Thyroid profiles, clinical symptoms, and laboratory indicators were analyzed. Quality of life was assessed using EQ-5D-3L and ThyPRO questionnaires. Complementary animal experiments were conducted to verify the effects of roxadustat on thyroid function. RESULTS: A total of 118 patients were finally enrolled in our study. Among patients with initially normal thyroid function, 31 developed euthyroid sick syndrome post-roxadustat treatment. Treatment significantly decreased TT3, FT3, FT4, and TSH levels, with TSH showing marked reduction within the first 10 weeks. Contrastingly, animal models exhibited decreased T3 but increased TSH levels, regardless of renal status. Blood lipid levels decreased in all patients, particularly in those with substantial TSH reduction. Despite thyroid alterations, quality-of-life scores remained unchanged between roxadustat-treated and untreated patients, with no overt clinical symptoms in either humans or animals. CONCLUSION: While roxadustat induces significant thyroid hormone suppression in patients, these alterations rarely manifest as clinical symptoms. Euthyroid sick syndrome is the predominant thyroid dysfunction pattern observed. Regular thyroid function monitoring is recommended during roxadustat therapy, particularly during the initial treatment phase when TSH changes are most pronounced.