Skip to main content
Top
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Peritoneal Dialysis | Research

Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study

Authors: Xuejie Zhang, Ruoyu Jia, Zhifang Zheng, Luhua Jiang, Yizhou Xu, Ashok Raj, Dong Sun

Published in: European Journal of Medical Research | Issue 1/2023

Login to get access

Abstract

Background

Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs).

Methods

This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60–100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency.

Results

Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, − 20.09 ng/mL; 95% CI, − 30.26 to − 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, − 7.87 nmol/L; 95% CI, − 12.11 to − 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study.

Conclusions

Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients.
Trial registration: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231).

Graphical abstract

Literature
1.
go back to reference Shaikh H, Hashmi MF, Aeddula NR. Anemia of chronic renal disease. In: StatPearls. StatPearls Publishing, Treasure Island (FL): 2022. Shaikh H, Hashmi MF, Aeddula NR. Anemia of chronic renal disease. In: StatPearls. StatPearls Publishing, Treasure Island (FL): 2022.
2.
go back to reference Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. Am J Kidney Dis. 2018;71:423–35.CrossRefPubMed Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. Am J Kidney Dis. 2018;71:423–35.CrossRefPubMed
3.
5.
go back to reference Requena-Ibáñez JA, Santos-Gallego CG, Rodriguez-Cordero A, Zafar MU, Badimon JJ. Prolyl hydroxylase inhibitors: a new opportunity in renal and myocardial protection. Cardiovasc Drugs Ther. 2022;36:1187–96.CrossRefPubMed Requena-Ibáñez JA, Santos-Gallego CG, Rodriguez-Cordero A, Zafar MU, Badimon JJ. Prolyl hydroxylase inhibitors: a new opportunity in renal and myocardial protection. Cardiovasc Drugs Ther. 2022;36:1187–96.CrossRefPubMed
6.
go back to reference Perlman RL, Zhao J, Fuller DS, et al. International anemia prevalence and management in peritoneal dialysis patients. Perit Dial Int. 2019;39:539–46.CrossRefPubMed Perlman RL, Zhao J, Fuller DS, et al. International anemia prevalence and management in peritoneal dialysis patients. Perit Dial Int. 2019;39:539–46.CrossRefPubMed
7.
go back to reference Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287:153–70.CrossRefPubMed Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287:153–70.CrossRefPubMed
8.
go back to reference Hou L, Lu J, Jiang X, Guo X, Ma C, Cheng X. Analytical evaluation of three soluble transferrin receptor measurement systems for diagnosis of iron deficiency anemia: a retrospective study. J Clin Lab Anal. 2020;34: e23342.CrossRefPubMedPubMedCentral Hou L, Lu J, Jiang X, Guo X, Ma C, Cheng X. Analytical evaluation of three soluble transferrin receptor measurement systems for diagnosis of iron deficiency anemia: a retrospective study. J Clin Lab Anal. 2020;34: e23342.CrossRefPubMedPubMedCentral
9.
go back to reference Pfeiffer CM, Looker AC. Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges. Am J Clin Nutr. 2017;106:1606S-1614S.CrossRefPubMedPubMedCentral Pfeiffer CM, Looker AC. Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges. Am J Clin Nutr. 2017;106:1606S-1614S.CrossRefPubMedPubMedCentral
11.
go back to reference Weir MR. Managing anemia across the stages of kidney disease in those hyporesponsive to erythropoiesis-stimulating agents. Am J Nephrol. 2021;52:450–66.CrossRefPubMed Weir MR. Managing anemia across the stages of kidney disease in those hyporesponsive to erythropoiesis-stimulating agents. Am J Nephrol. 2021;52:450–66.CrossRefPubMed
13.
go back to reference Locatelli F, Del Vecchio L, De Nicola L, Minutolo R. Are all erythropoiesis-stimulating agents created equal? Nephrol Dial Transplant. 2021;36:1369–77.CrossRefPubMed Locatelli F, Del Vecchio L, De Nicola L, Minutolo R. Are all erythropoiesis-stimulating agents created equal? Nephrol Dial Transplant. 2021;36:1369–77.CrossRefPubMed
14.
go back to reference Souza E, Cho KH, Harris ST, Flindt NR, Watt RK, Pai AB. Hypoxia-inducible factor prolyl hydroxylase inhibitors: a paradigm shift for treatment of anemia in chronic kidney disease? Expert Opin Investig Drugs. 2020;29:831–44.CrossRefPubMed Souza E, Cho KH, Harris ST, Flindt NR, Watt RK, Pai AB. Hypoxia-inducible factor prolyl hydroxylase inhibitors: a paradigm shift for treatment of anemia in chronic kidney disease? Expert Opin Investig Drugs. 2020;29:831–44.CrossRefPubMed
16.
go back to reference Locatelli F, Del Vecchio L. Hypoxia-inducible factor-prolyl hydroxyl domain inhibitors: from theoretical superiority to clinical noninferiority compared with current ESAs? J Am Soc Nephrol. 2022;33:1966–79.CrossRefPubMedPubMedCentral Locatelli F, Del Vecchio L. Hypoxia-inducible factor-prolyl hydroxyl domain inhibitors: from theoretical superiority to clinical noninferiority compared with current ESAs? J Am Soc Nephrol. 2022;33:1966–79.CrossRefPubMedPubMedCentral
19.
go back to reference Sugahara M, Tanaka T, Nangaku M. Future perspectives of anemia management in chronic kidney disease using hypoxia-inducible factor-prolyl hydroxylase inhibitors. Pharmacol Ther. 2022;239: 108272.CrossRefPubMed Sugahara M, Tanaka T, Nangaku M. Future perspectives of anemia management in chronic kidney disease using hypoxia-inducible factor-prolyl hydroxylase inhibitors. Pharmacol Ther. 2022;239: 108272.CrossRefPubMed
20.
go back to reference Chen N, Hao C, Peng X, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med. 2019;381:1001–10.CrossRefPubMed Chen N, Hao C, Peng X, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med. 2019;381:1001–10.CrossRefPubMed
21.
23.
go back to reference Aschemeyer S, Qiao B, Stefanova D, et al. Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin. Blood. 2018;131:899–910.CrossRefPubMedPubMedCentral Aschemeyer S, Qiao B, Stefanova D, et al. Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin. Blood. 2018;131:899–910.CrossRefPubMedPubMedCentral
25.
go back to reference Batchelor EK, Kapitsinou P, Pergola PE, Kovesdy CP, Jalal DI. Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment. J Am Soc Nephrol. 2020;31:456–68.CrossRefPubMedPubMedCentral Batchelor EK, Kapitsinou P, Pergola PE, Kovesdy CP, Jalal DI. Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment. J Am Soc Nephrol. 2020;31:456–68.CrossRefPubMedPubMedCentral
26.
27.
go back to reference Gafter-Gvili A, Schechter A, Rozen-Zvi B. Iron deficiency anemia in chronic kidney disease. Acta Haematol. 2019;142:44–50.CrossRefPubMed Gafter-Gvili A, Schechter A, Rozen-Zvi B. Iron deficiency anemia in chronic kidney disease. Acta Haematol. 2019;142:44–50.CrossRefPubMed
28.
go back to reference Schwartz AJ, Das NK, Ramakrishnan SK, et al. Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload. J Clin Invest. 2019;129:336–48.CrossRefPubMed Schwartz AJ, Das NK, Ramakrishnan SK, et al. Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload. J Clin Invest. 2019;129:336–48.CrossRefPubMed
29.
go back to reference Babitt JL, Eisenga MF, Haase VH, et al. Controversies in optimal anemia management: conclusions from a kidney disease: improving global outcomes (KDIGO) conference. Kidney Int. 2021;99:1280–95.CrossRefPubMed Babitt JL, Eisenga MF, Haase VH, et al. Controversies in optimal anemia management: conclusions from a kidney disease: improving global outcomes (KDIGO) conference. Kidney Int. 2021;99:1280–95.CrossRefPubMed
30.
go back to reference Sierpinski R, Josiak K, Suchocki T, et al. High soluble transferrin receptor in patients with heart failure: a measure of iron deficiency and a strong predictor of mortality. Eur J Heart Fail. 2021;23:919–32.CrossRefPubMed Sierpinski R, Josiak K, Suchocki T, et al. High soluble transferrin receptor in patients with heart failure: a measure of iron deficiency and a strong predictor of mortality. Eur J Heart Fail. 2021;23:919–32.CrossRefPubMed
31.
go back to reference Daude S, Remen T, Chateau T, et al. Comparative accuracy of ferritin, transferrin saturation and soluble transferrin receptor for the diagnosis of iron deficiency in inflammatory bowel disease. Aliment Pharmacol Ther. 2020;51:1087–95.CrossRefPubMed Daude S, Remen T, Chateau T, et al. Comparative accuracy of ferritin, transferrin saturation and soluble transferrin receptor for the diagnosis of iron deficiency in inflammatory bowel disease. Aliment Pharmacol Ther. 2020;51:1087–95.CrossRefPubMed
32.
go back to reference Weidmann H, Bannasch JH, Waldeyer C, et al. Iron metabolism contributes to prognosis in coronary artery disease: prognostic value of the soluble transferrin receptor within the atherogene study. J Am Heart Assoc. 2020;9: e015480.CrossRefPubMedPubMedCentral Weidmann H, Bannasch JH, Waldeyer C, et al. Iron metabolism contributes to prognosis in coronary artery disease: prognostic value of the soluble transferrin receptor within the atherogene study. J Am Heart Assoc. 2020;9: e015480.CrossRefPubMedPubMedCentral
33.
go back to reference Zhu S, Liu C, Zhao C, et al. Increased serum soluble transferrin receptor levels were associated with high prevalence of cardiovascular diseases: insights from the national health and nutrition examination survey 2017–2018. Front Cell Dev Biol. 2022;10: 874846.CrossRefPubMedPubMedCentral Zhu S, Liu C, Zhao C, et al. Increased serum soluble transferrin receptor levels were associated with high prevalence of cardiovascular diseases: insights from the national health and nutrition examination survey 2017–2018. Front Cell Dev Biol. 2022;10: 874846.CrossRefPubMedPubMedCentral
34.
go back to reference Zielniok K, Burdzinska A, Paczek L. Roxadustat for anemia in patients with chronic kidney disease. N Engl J Med. 2020;383: e3.CrossRefPubMed Zielniok K, Burdzinska A, Paczek L. Roxadustat for anemia in patients with chronic kidney disease. N Engl J Med. 2020;383: e3.CrossRefPubMed
35.
go back to reference Chen N, Hao C, Liu BC, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med. 2019;381:1011–22.CrossRefPubMed Chen N, Hao C, Liu BC, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med. 2019;381:1011–22.CrossRefPubMed
36.
go back to reference Di Iorio BR, Bellasi A, Raphael KL, et al. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI study. J Nephrol. 2019;32:989–1001.CrossRefPubMedPubMedCentral Di Iorio BR, Bellasi A, Raphael KL, et al. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI study. J Nephrol. 2019;32:989–1001.CrossRefPubMedPubMedCentral
37.
go back to reference Zhang DL, Wu J, Shah BN, et al. Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. 2018;359:1520–3.CrossRefPubMedPubMedCentral Zhang DL, Wu J, Shah BN, et al. Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. 2018;359:1520–3.CrossRefPubMedPubMedCentral
38.
go back to reference Wunderer F, Traeger L, Sigurslid HH, Meybohm P, Bloch DB, Malhotra R. The role of hepcidin and iron homeostasis in atherosclerosis. Pharmacol Res. 2020;153: 104664.CrossRefPubMedPubMedCentral Wunderer F, Traeger L, Sigurslid HH, Meybohm P, Bloch DB, Malhotra R. The role of hepcidin and iron homeostasis in atherosclerosis. Pharmacol Res. 2020;153: 104664.CrossRefPubMedPubMedCentral
Metadata
Title
Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study
Authors
Xuejie Zhang
Ruoyu Jia
Zhifang Zheng
Luhua Jiang
Yizhou Xu
Ashok Raj
Dong Sun
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01465-0

Other articles of this Issue 1/2023

European Journal of Medical Research 1/2023 Go to the issue