Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in maintenance dialysis: a meta-analysis.


Journal

Clinical and experimental nephrology
ISSN: 1437-7799
Titre abrégé: Clin Exp Nephrol
Pays: Japan
ID NLM: 9709923

Informations de publication

Date de publication:
Nov 2022
Historique:
received: 31 08 2021
accepted: 05 08 2022
pubmed: 26 8 2022
medline: 20 10 2022
entrez: 25 8 2022
Statut: ppublish

Résumé

Anaemia is a common complication of end-stage renal disease (ESRD) that relies on dialysis. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) is a new class of small-molecule oral drugs for the treatment of anaemia in chronic kidney disease. They demonstrate several advantages over traditional exogenous erythropoietin (EPO). We conducted a meta-analysis of studies that compared the efficacy of HIF-PHI in erythropoiesis and iron metabolism, and its safety with EPO in maintenance dialysis patients. A sensitive search strategy in the PubMed, EMBASE and Cochrane databases identified all citations for randomised controlled trials (RCTs) comparing HIF-PHI agents with EPO/placebo through December 2021. Fourteen RCTs were identified, which included 2738 patients. No statistical difference was found in haemoglobin increase (p = 0.37) between HIF-PHI treatment and EPO using the random-effects model. HIF-PHI administration upregulated transferrin (MD 36.12, 95% CI 27.04-45.20) and soluble transferrin receptors (sTfR) (MD 1.28, 95% CI 0.44-2.13), but did not statistically reduce hepcidin level (p = 0.37). Total and LDL-cholestrol levels were suppressed by HIF-PHI (MD - 0.99, 95% CI - 1.34 to  - 0.63) (MD - 0.99, 95% CI - 1.34 to - 0.64), while triglyceride (TG) was not different between HIF-PHI and EPO (p = 0.74). The total incident rates of treatment-emergent adverse events (TEAE) (p = 0.20) from HIF-PHI treatment were not different from those of erythropoietin, while the treatment-emergent serious adverse events (TSAE) (p = 0.02) were higher in the HIF-PHI group than those in the EPO controls with the fixed-effect model. HIF-PHI could effectively upregulate and maintain haemoglobin levels in patients with anaemia receiving maintenance dialysis. Furthermore, HIF-PHI could elevate iron metabolism activity and utility without inducing treatment-associated serious adverse events. Robust data from larger RCTs with longer treatment duration and follow-up are needed.

Sections du résumé

BACKGROUND BACKGROUND
Anaemia is a common complication of end-stage renal disease (ESRD) that relies on dialysis. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) is a new class of small-molecule oral drugs for the treatment of anaemia in chronic kidney disease. They demonstrate several advantages over traditional exogenous erythropoietin (EPO). We conducted a meta-analysis of studies that compared the efficacy of HIF-PHI in erythropoiesis and iron metabolism, and its safety with EPO in maintenance dialysis patients.
METHODS METHODS
A sensitive search strategy in the PubMed, EMBASE and Cochrane databases identified all citations for randomised controlled trials (RCTs) comparing HIF-PHI agents with EPO/placebo through December 2021.
RESULTS RESULTS
Fourteen RCTs were identified, which included 2738 patients. No statistical difference was found in haemoglobin increase (p = 0.37) between HIF-PHI treatment and EPO using the random-effects model. HIF-PHI administration upregulated transferrin (MD 36.12, 95% CI 27.04-45.20) and soluble transferrin receptors (sTfR) (MD 1.28, 95% CI 0.44-2.13), but did not statistically reduce hepcidin level (p = 0.37). Total and LDL-cholestrol levels were suppressed by HIF-PHI (MD - 0.99, 95% CI - 1.34 to  - 0.63) (MD - 0.99, 95% CI - 1.34 to - 0.64), while triglyceride (TG) was not different between HIF-PHI and EPO (p = 0.74). The total incident rates of treatment-emergent adverse events (TEAE) (p = 0.20) from HIF-PHI treatment were not different from those of erythropoietin, while the treatment-emergent serious adverse events (TSAE) (p = 0.02) were higher in the HIF-PHI group than those in the EPO controls with the fixed-effect model.
CONCLUSION CONCLUSIONS
HIF-PHI could effectively upregulate and maintain haemoglobin levels in patients with anaemia receiving maintenance dialysis. Furthermore, HIF-PHI could elevate iron metabolism activity and utility without inducing treatment-associated serious adverse events. Robust data from larger RCTs with longer treatment duration and follow-up are needed.

Identifiants

pubmed: 36006596
doi: 10.1007/s10157-022-02263-4
pii: 10.1007/s10157-022-02263-4
doi:

Substances chimiques

Hepcidins 0
Prolyl-Hydroxylase Inhibitors 0
Receptors, Transferrin 0
Transferrin 0
Triglycerides 0
Erythropoietin 11096-26-7
Iron E1UOL152H7

Types de publication

Journal Article Meta-Analysis Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1043-1054

Subventions

Organisme : National Natural Science Foundation of China
ID : 82000689
Organisme : National Natural Science Foundation of China
ID : 81974094
Organisme : China Postdoctoral Science Foundation
ID : 2021M691212

Informations de copyright

© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.

Références

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Auteurs

Meiyan Wu (M)

Department of Nephrology, The First Hospital of Jilin University, Jilin University, Changchun, China.

Chongsen Zang (C)

Department of Nephrology, The First Hospital of Jilin University, Jilin University, Changchun, China.

Fuzhe Ma (F)

Department of Nephrology, The First Hospital of Jilin University, Jilin University, Changchun, China.

Bin Chen (B)

Department of Nephrology, The First Hospital of Jilin University, Jilin University, Changchun, China.

Juan Liu (J)

Department of Nephrology, The First Hospital of Jilin University, Jilin University, Changchun, China.

Zhonggao Xu (Z)

Department of Nephrology, The First Hospital of Jilin University, Jilin University, Changchun, China. zhonggao@jlu.edu.cn.

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