MO797: Roxadustat Decreases Serum Lipids Levels in Hemodialysis Patients

Abstract

Abstract BACKGROUND AND AIMS The activity of hypoxia-inducible factor (HIF), an oxygen-sensitive transcription factor involved in erythropoiesis, is regulated by HIF-prolyl hydroxylases. With decreased oxygen tension, the activity of these enzymes is suppressed, resulting in increased erythropoiesis [1]. Roxadustat is an oral HIF-prolyl hydroxylase inhibitor (HIF-PHI) developed for dialysis-dependent chronic kidney disease (CKD) anemia. While the impact of HIF-PHI on mean hemoglobin (Hb) change in patients on hemodialysis (HD) has already been investigated [2], its effects on serum lipid levels have yet to be explored. Clarifying such effects is particularly important because chronic HD patients usually have lower plasma high-density lipoprotein (HDL)-cholesterol (C) levels than healthy subjects. The aim of this study is to investigate the effects of roxadustat on serum lipid levels in HD patients. METHOD Study 1: This multicenter observational cohort study investigated the demographic and clinical information of 258 patients on HD (73 women and 185 men) who were being treated for anemia by HIF-PHI between 1 February 2020 and 31 May 2021, at Zenjinkai Group dialysis centers in Japan. Study 2: This study evaluated the efficacy of roxadustat in 24 patients (3 women and 21 men) for HD-dependent CKD anemia and dyslipidemia >24 weeks. RESULTS Study 1: The mean age and HD periods were 71.2 ± 12.2 and 5.5 ± 6.6 years, respectively. The patient's CKDs were diabetic nephropathy (n = 72; 27.9%), chronic glomerular nephritis (CGN) (n = 36; 14%), nephrosclerosis (n = 32; 12.4%) and other pathologies (n = 118; 45.7%). HIF-PH inhibitors used for patients on HD were roxadustat (n = 105), daprodustat (n = 117), vadadustat (n = 14) and enadustat (n = 22). Study 2: The mean age and HD periods were 76.5 ± 7.7 and 5.3 ± 3.9 years, respectively. The patient's CKDs were CGN (n = 6; 25%), nephrosclerosis (n = 6; 25%), diabetic nephropathy (n = 4; 16.7%), unknown pathologies (n = 4; 16.7%) and others (n = 4; 16.7%). Roxadustat treatment did not lead to a significant change in mean Hb values (from 10.4 ± 0.8 to 10.5 ± 0.9 g/dL). There were no significant changes in mean triglycerides (TG), transferrin saturation (TSAT) or ferritin. However, there was a statistically significant decrease (P < .001) in mean total cholesterol (TC) (from 144.0 ± 35.6 to 121.3 ± 38.5 mg/dL), low-density lipoprotein (LDL)-C (from 79.8 ± 26.6 to 62.8 ± 26.2 mg/dL) and HDL-C (from 45.0 ± 12.6 to 38.4 ± 11.9 mg/dL). Furthermore, there were also significant increases in mean serum iron (from 68.1 ± 17.4 to 81.8 ± 31.1 μg/dL; P = .01) and the mean total iron-binding capacity (TIBC) (from 220.0 ± 46.7 to 265.1 ± 54.7 μg/dL; P < .001). Case report: A 56-year-old woman who had undergone HD for 13 years due to CKD due to diabetic nephropathy was hospitalized with cerebral infraction, peripheral arterial disease, heart failure and ischemic heart disease. The patient was treated with percutaneous coronary intervention (PCI) and started on 100 mg of roxadustat 3 times a week. After roxadustat treatment, the following parameters increased: Hb (from 10.7 to 10.8 g/dL), ferritin (from 74 to 103 ng/mL) and TIBC (from 204 to 223 μg/dL). On the other hand, the following parameters decreased: TC (from 325 to 125 mg/dL), TG (from 318 to 165 mg/dL), HDL-C (from 41 to 33 mg/dL) and LDL-C (from 227 to 55 mg/dL). The patient was discharged from the hospital after 3 months. CONCLUSION Roxadustat treatment improves iron metabolism, keeps Hb levels stable and significantly decreases mean LDL-C and HDL-C. Therefore, this drug may have useful effects on dyslipidemia in patients on HD.