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Meta-Analysis
. 2022 Aug 25;8(8):CD013751.
doi: 10.1002/14651858.CD013751.pub2.

Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease

Patrizia Natale  1   2   3 , Suetonia C Palmer  4 , Allison Jaure  2   5 , Elisabeth M Hodson  2   6 , Marinella Ruospo  1 , Tess E Cooper  2   6 , Deirdre Hahn  7 , Valeria M Saglimbene  1   2 , Jonathan C Craig  6   8 , Giovanni Fm Strippoli  1   2   6
Affiliations
Meta-Analysis

Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease

Patrizia Natale et al. Cochrane Database Syst Rev. .

Abstract

Background: Anaemia occurs in chronic kidney disease (CKD) and is more prevalent with lower levels of kidney function. Anaemia in CKD is associated with death related to cardiovascular (CV) disease and infection. Established treatments include erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions. Oral hypoxia-inducible factors (HIF) stabilisers are now available to manage anaemia in people with CKD.

Objectives: We aimed to assess the benefits and potential harms of HIF stabilisers for the management of anaemia in people with CKD.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 22 November 2021 through contact with the Information Specialist using search terms relevant to our review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.

Selection criteria: Randomised and quasi-randomised studies evaluating hypoxia-inducible factors stabilisers compared to placebo, standard care, ESAs or iron supplementation in people with CKD were included.

Data collection and analysis: Five authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects pair-wise meta-analysis and expressed as a relative risk (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Evidence certainty was assessed using GRADE.

Main results: We included 51 studies randomising 30,994 adults. These studies compared HIF stabilisers to either placebo or an ESA. Compared to placebo, HIF stabiliser therapy had uncertain effects on CV death (10 studies, 1114 participants): RR 3.68, 95% CI 0.19 to 70.21; very low certainty evidence), and nonfatal myocardial infarction (MI) (3 studies, 822 participants): RR 1.29, 95% CI 0.31 to 5.36; I² = 0%; very low certainty evidence), probably decreases the proportion of patients requiring blood transfusion (8 studies, 4329 participants): RR 0.51, 95% CI 0.44 to 0.60; I² = 0%; moderate certainty evidence), and increases the proportion of patients reaching the target haemoglobin (Hb) (10 studies, 5102 participants): RR 8.36, 95% CI 6.42 to 10.89; I² = 37%; moderate certainty evidence). Compared to ESAs, HIF stabiliser therapy may make little or no difference to CV death (17 studies, 10,340 participants): RR 1.05, 95% CI 0.88 to 1.26; I² = 0%; low certainty evidence), nonfatal MI (7 studies, 7765 participants): RR 0.91, 95% CI 0.76 to 1.10; I² = 0%; low certainty evidence), and nonfatal stroke (5 studies, 7285 participants): RR 1.06, 95% CI 0.71 to 1.56; I² = 8%; low certainty evidence), and had uncertain effects on fatigue (2 studies, 3471 participants): RR 0.80, 95% CI 0.56 to 1.16; I² = 0%; very low certainty evidence). HIF stabiliser therapy probably decreased the proportion of patients requiring blood transfusion (11 studies, 10,786 participants): RR 0.87, 95% CI 0.76 to 1.00; I² = 25%; moderate certainty evidence), but may make little or no difference on the proportion of patients reaching the target Hb (14 studies, 4601 participants): RR 1.00, 95% CI 0.93 to 1.07; I² = 70%; low certainty evidence), compared to ESA. The effect of HIF stabilisers on hospitalisation for heart failure, peripheral arterial events, loss of unassisted dialysis vascular access patency, access intervention, cancer, infection, pulmonary hypertension and diabetic nephropathy was uncertain. None of the included studies reported life participation. Adverse events were rarely and inconsistently reported.

Authors' conclusions: HIF stabiliser management of anaemia had uncertain effects on CV death, fatigue, death (any cause), CV outcomes, and kidney failure compared to placebo or ESAs. Compared to placebo or ESAs, HIF stabiliser management of anaemia probably decreased the proportion of patients requiring blood transfusions, and probably increased the proportion of patients reaching the target Hb when compared to placebo.

Trial registration: ClinicalTrials.gov NCT02019719 NCT01964196 NCT02952092 NCT02969655 NCT02988973 NCT01887600 NCT01750190 NCT02879305 NCT03029208 NCT02876835 NCT03409107 NCT03400033 NCT00761657 NCT01047397 NCT02652806 NCT02652819 NCT01596855 NCT01599507 NCT02021370 NCT02021409 NCT01975818 NCT02021318 NCT02052310 NCT01977573 NCT02865850 NCT02892149 NCT01977482 NCT03543657 NCT03350321 NCT03350347 NCT03439137 NCT03329196 NCT02791763 NCT01888445 NCT03054337 NCT02174627 NCT01906489 NCT02680574 NCT02648347 NCT01147666 NCT02278341 NCT02174731 NCT02273726 NCT02780726 NCT02780141 NCT03457701 NCT03029247 NCT02689206 NCT01414075 NCT03054350 NCT01587898 NCT01587924 NCT01381094 NCT01679587 NCT01971164 NCT03992066 NCT04059913 NCT01244763 NCT03799627 NCT03446612 NCT04012957 NCT04215120 NCT04027517 NCT04134026 NCT04313153.

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Conflict of interest statement

  1. Patrizia Natale: no relevant interests were disclosed

  2. Suetonia C Palmer: no relevant interests were disclosed

  3. Allison Jaure: no relevant interests were disclosed

  4. Elisabeth M Hodson: no relevant interests were disclosed

  5. Marinella Ruospo: no relevant interests were disclosed

  6. Tess E Cooper: no relevant interests were disclosed

  7. Deirdre Hahn: no relevant interests were disclosed

  8. Valeria Saglimbene: no relevant interests were disclosed

  9. Jonathan Craig: no relevant interests were disclosed

  10. Giovanni FM Strippoli: no relevant interests were disclosed

Figures

1
1
Flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 2 Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), outcome: 2.1 Cardiovascular death.
1.1
1.1. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 1: Cardiovascular death
1.2
1.2. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 2: Death (any cause)
1.3
1.3. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 3: Nonfatal myocardial infarction
1.4
1.4. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 4: Fatal or nonfatal myocardial infarction (overall)
1.5
1.5. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 5: Nonfatal stroke
1.6
1.6. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 6: Fatal or nonfatal stroke (overall)
1.7
1.7. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 7: Peripheral arterial events
1.8
1.8. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 8: Transfusion
1.9
1.9. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 9: Proportion reaching target haemoglobin
1.10
1.10. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 10: Kidney failure
1.11
1.11. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 11: Thrombosis
1.12
1.12. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 12: Loss of unassisted patency (stenosis)
1.13
1.13. Analysis
Comparison 1: Hypoxia‐inducible factor (HIF) stabiliser versus placebo, Outcome 13: Hyperkalaemia
2.1
2.1. Analysis
Comparison 2: Analyses for SOF table 1 stratifying by CKD stage (HIF versus placebo), Outcome 1: Cardiovascular death
2.2
2.2. Analysis
Comparison 2: Analyses for SOF table 1 stratifying by CKD stage (HIF versus placebo), Outcome 2: Nonfatal myocardial infarction
2.3
2.3. Analysis
Comparison 2: Analyses for SOF table 1 stratifying by CKD stage (HIF versus placebo), Outcome 3: Transfusion
2.4
2.4. Analysis
Comparison 2: Analyses for SOF table 1 stratifying by CKD stage (HIF versus placebo), Outcome 4: Proportion reaching target haemoglobin
3.1
3.1. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 1: Cardiovascular death
3.2
3.2. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 2: Fatigue
3.3
3.3. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 3: Death (any cause)
3.4
3.4. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 4: Nonfatal myocardial infarction
3.5
3.5. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 5: Fatal or nonfatal myocardial infarction (overall)
3.6
3.6. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 6: Nonfatal stroke
3.7
3.7. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 7: Fatal or nonfatal stroke (overall)
3.8
3.8. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 8: Nonfatal hospitalisation for heart failure
3.9
3.9. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 9: Fatal or nonfatal hospitalisation for heart failure
3.10
3.10. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 10: Peripheral arterial event
3.11
3.11. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 11: Transfusion
3.12
3.12. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 12: Proportion reaching target haemoglobin
3.13
3.13. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 13: Kidney failure
3.14
3.14. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 14: Thrombosis
3.15
3.15. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 15: Loss of unassisted patency (occlusion/stenosis)
3.16
3.16. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 16: Access intervention
3.17
3.17. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 17: Cancer
3.18
3.18. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 18: Infection
3.19
3.19. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 19: Hyperkalaemia
3.20
3.20. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 20: Pulmonary hypertension
3.21
3.21. Analysis
Comparison 3: Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA), Outcome 21: Diabetic retinopathy
4.1
4.1. Analysis
Comparison 4: Analyses for SOF table 2 stratifying by CKD stage (HIF versus ESA), Outcome 1: Cardiovascular death
4.2
4.2. Analysis
Comparison 4: Analyses for SOF table 2 stratifying by CKD stage (HIF versus ESA), Outcome 2: Fatigue
4.3
4.3. Analysis
Comparison 4: Analyses for SOF table 2 stratifying by CKD stage (HIF versus ESA), Outcome 3: Nonfatal myocardial infarction
4.4
4.4. Analysis
Comparison 4: Analyses for SOF table 2 stratifying by CKD stage (HIF versus ESA), Outcome 4: Nonfatal stroke
4.5
4.5. Analysis
Comparison 4: Analyses for SOF table 2 stratifying by CKD stage (HIF versus ESA), Outcome 5: Transfusion
4.6
4.6. Analysis
Comparison 4: Analyses for SOF table 2 stratifying by CKD stage (HIF versus ESA), Outcome 6: Proportion reaching target haemoglobin
5.1
5.1. Analysis
Comparison 5: Subgroup analysis: stage CKD (HIF versus ESA), Outcome 1: Proportion reaching target haemoglobin
5.2
5.2. Analysis
Comparison 5: Subgroup analysis: stage CKD (HIF versus ESA), Outcome 2: Thrombosis
6.1
6.1. Analysis
Comparison 6: Subgroup analysis: duration of therapy (HIF versus ESA), Outcome 1: Proportion reaching target haemoglobin
6.2
6.2. Analysis
Comparison 6: Subgroup analysis: duration of therapy (HIF versus ESA), Outcome 2: Thrombosis
7.1
7.1. Analysis
Comparison 7: Subgroup analysis: frequency of administration (HIF versus ESA), Outcome 1: Proportion reaching target haemoglobin
7.2
7.2. Analysis
Comparison 7: Subgroup analysis: frequency of administration (HIF versus ESA), Outcome 2: Thrombosis
8.1
8.1. Analysis
Comparison 8: Subgroup analysis: phase 2 versus phase 3 studies (HIF versus ESA), Outcome 1: Proportion reaching target haemoglobin
8.2
8.2. Analysis
Comparison 8: Subgroup analysis: phase 2 versus phase 3 studies (HIF versus ESA), Outcome 2: Thrombosis
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References

References to studies included in this review

Akizawa 2017 {published data only}
    1. Akizawa T, Tsubakihara Y, Nangaku M, Endo Y, Nakajima H, Kohno T, et al. Effects of daprodustat, a novel hypoxia-inducible factor prolyl hydroxylase inhibitor on anemia management in Japanese hemodialysis subjects. American Journal of Nephrology 2017;45(2):127-35. [MEDLINE: ] - PubMed
    1. Endo Y, Kohno T, Imai Y, Kawase N, Hara K, Lepore JJ, et al. A 4 -week dose response study of the hypoxia inducible factor-prolyl hydroxylase inhibitor GSK1278863 in Japanese anemic haemodialysis subjects [abstract no: SA-PO819]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):818A.
    1. NCT02019719. Study to evaluate the safety, efficacy and pharmacokinetics of GSK1278863 in Japanese hemodialysis-dependent subjects with anemia associated with chronic kidney disease [A 4-week, phase ii, randomized, double-blind, dose-ranging, placebo-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of GSK1278863 in Japanese hemodialysis-dependent subjects with anemia associated with chronic kidney disease]. clinicaltrials.gov/show/NCT02019719 (first received 24 December 2013).
Akizawa 2019 {published data only}
    1. Akizawa T, Iwasaki M, Otsuka T, Reusch M, Misumi T. Roxadustat for the treatment of chronic kidney disease-associated anemia in Japanese patients not on dialysis [abstract no: FR-PO1142]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):7B.
    1. Akizawa T, Iwasaki M, Otsuka T, Reusch M, Misumi T. Roxadustat treatment of chronic kidney disease-associated anemia in Japanese patients not on dialysis: a phase 2, randomized, double-blind, placebo-controlled trial. Advances in Therapy 2019;36(6):1438-54. [MEDLINE: ] - PMC - PubMed
Akizawa 2020a {published data only}
    1. Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Authors' Reply. Journal of the American Society of Nephrology 2021;32(4):1005-7. [MEDLINE: ] - PMC - PubMed
    1. Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Phase 3, randomized, double-blind, active-comparator (darbepoetin alfa) conversion study of oral roxadustat in CKD patients with anemia on hemodialysis in Japan [abstract no: TH-PO1151]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):B4. - PMC - PubMed
    1. Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Phase 3, randomized, double-blind, active-comparator (darbepoetin alfa) study of oral roxadustat in CKD patients with anemia on hemodialysis in Japan. Journal of the American Society of Nephrology 2020;31(7):1628-39. [MEDLINE: ] - PMC - PubMed
    1. Akizawa T, Yamaguchi Y, Majikawa Y, Reusch M. Factors affecting the doses of roxadustat vs darbepoetin alfa for anemia treatment in hemodialysis patients. Therapeutic Apheresis & Dialysis 2021;25(5):575-85. [MEDLINE: ] - PMC - PubMed
    1. Astellas1517-CL-0307. A study of intermittent oral dosing of ASP1517 in hemodialysis chronic kidney disease patients with anemia [A phase 3, multi-center, randomized, 2-arm parallel, double-blind, active-comparator (darbepoetin alfa) conversion study of intermittent oral dosing of ASP1517 in hemodialysis chronic kidney disease patients with anemia]. www.clinicaltrials.astellas.com/study/?pid=1517-CL-0307 (accessed 4 May 2022).
Akizawa 2020c {published data only}
    1. Akizawa T, Nangaku M, Yonekawa T, Okuda N, Kawamatsu S, Onoue T, et al. Efficacy and safety of daprodustat compared with darbepoetin alfa in Japanese hemodialysis patients with anemia: a randomized, double-blind, phase 3 trial. Clinical Journal of the American Society of Nephrology: CJASN 2020;15(8):1155-65. [MEDLINE: ] - PMC - PubMed
    1. Ozeki H, Akizawa T, Nangaku M, Yonekawa T, Okuda N, Kawamatsu S, et al. Efficacy and safety of daprodustat compared with darbepoetin alfa in Japanese hemodialysis patients with anemia: A randomized, double-blind, phase 3 trial [abstract no: SaO036]. Nephrology Dialysis Transplantation 2019;34(Suppl 1):a350. [EMBASE: 631305259] - PMC - PubMed
Akizawa 2020f {published data only}
    1. Akizawa T, Iwasaki M, Otsuka T, Yamaguchi Y, Reusch M. A phase 3, multicenter, randomized, open-label, active comparator conversion study of roxadustat in non-dialysis-dependent (NDD) patients with anemia in chronic kidney disease (CKD) [abstract no: POS-244]. Kidney International Reports 2021;6(4 Suppl):S103. [EMBASE: 2011682459]
    1. Akizawa T, Iwasaki M, Otsuka T, Yamaguchi Y, Reusch M. A phase 3, multicenter, randomized, open-label, active comparator conversion study of roxadustat in non-dialysis-dependent (NDD) patients with anemia in CKD [abstract no: PO0269]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):134. [EMBASE: 633699036]
    1. Nguyen QD, Sepah YJ, Yamaguchi Y, Otsuka T, Majikawa Y, Reusch M, et al. Ophthalmological effects of roxadustat in the treatment of anemia in dialysis-dependent and non-dialysis-dependent CKD patients: findings from two phase 3 studies [abstract no: PO0267]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):134. [EMBASE: 633698979]
Akizawa 2021 {published data only}
    1. Akizawa T, Iwasaki M, Otsuka T, Yamaguchi Y, Reusch M. Phase 3 study of roxadustat to treat anemia in non-dialysis-dependant CKD. Kidney International Reports 2021;6(7):1810-28. [MEDLINE: ] - PMC - PubMed
    1. Akizawa T, Tanaka-Amino K, Otsuka T, Yamaguchi Y. Factors affecting doses of roxadustat versus darbepoetin alfa for anemia in nondialysis patients. American Journal of Nephrology 2021;52(9):702-13. [MEDLINE: ] - PMC - PubMed
ALPS 2021 {published data only}
    1. Astellas 1517-CL-0608. Roxadustat in the treatment of anemia in chronic kidney disease patients not requiring dialysis [A phase 3, randomized, double-blind, placebo controlled study of the efficacy and safety of roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis]. www.trialsummaries.com/Study/StudyDetails?id=14384&tenant=MT_AST_9011 2019. - PMC - PubMed
    1. Esposito C, Csiky B, Tataradze A, Reusch M, Han C, Sulowicz W. Two phase 3, multicenter, randomized studies of intermittent oral roxadustat in anemic CKD patients on (PYRENEES) and not on (ALPS) dialysis [abstract no: SA-PO225]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):822. [EMBASE: 633767739]
    1. Pecoits-Filho R, Chan TM, Hardy E, Yu KH, Fishbane S. Roxadustat treatment results in consistent improvements in hemoglobin (Hb) vs. placebo: an analysis of three multinational randomized clinical trials in patients with non-dialysis-dependent CKD (NDD-CKD) [abstract no: TH-OR05]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):2. [EMBASE: 633697943]
    1. Rastogi A, Pecoits-Filho R, Fishbane S, Little DJ, Hardy E, Yu KH, et al. Roxadustat treatment corrects anemia to hemoglobin (HB) values ≥10 g/dL in the majority of patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) [abstract no: PO0264]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):133. [EMBASE: 633698803]
    1. Shutov E, Sulowicz W, Esposito C, Tataradze A, Andric B, Reusch M, et al. Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a phase 3, randomized, double-blind, placebo-controlled study (ALPS). Nephrology Dialysis Transplantation 2021;36(9):1629-39. [MEDLINE: ] - PMC - PubMed
ANDES 2021 {published data only}
    1. Coyne DW, Roger SD, Chou W, Besarab A, Leong R, Lee TT, et al. Roxadustat favorably modifies iron indices in patients with non-dialysis-dependent CKD-related anemia [abstract no: PO0262]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):132. [EMBASE: 633698686]
    1. Coyne DW, Roger SD, Shin S, Kim SG, Cadena AA, Moustafa MA, et al. Roxadustat for CKD-related anemia in non-dialysis patients. Kidney International Reports 2021;6(3):624-35. [MEDLINE: ] - PMC - PubMed
    1. Coyne DW, Roger SD, Shin SK, Kim SG, Cadena AA, Moustafa MA, et al. ANDES: A phase 3, randomized, double-blind, placebo controlled study of the efficacy and safety of roxadustat for the treatment of anemia in CKD patients not on dialysis [abstract no: SA-PO0228]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):822-3. [EMBASE: 633767955]
    1. Pecoits-Filho R, Chan TM, Hardy E, Yu KHP, Fishbane S. Roxadustat treatment results in consistent improvements in hemoglobin (Hb) vs. placebo: an analysis of three multinational randomized clinical trials in patients with non-dialysis-dependent CKD (NDD-CKD) [abstract no: TH-OR05]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):2. [EMBASE: 633697943]
    1. Rastogi A, Pecoits-Filho R, Fishbane S, Little DJ, Hardy E, Yu KH, et al. Roxadustat treatment corrects anemia to hemoglobin (HB) values ≥10 g/dL in the majority of patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) [abstract no: PO0264]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):133. [EMBASE: 633698803]
ASCEND‐D 2021 {published data only}
    1. Singh AK, Blackorby A, Cizman B, Carroll K, Cobitz AR, Davies R, et al. Study design and baseline characteristics of patients on dialysis in the ASCEND-D trial. Nephrology Dialysis Transplantation 2021;37(5):960-72. [MEDLINE: ] [MEDLINE: ] - PMC - PubMed
    1. Singh AK, Blackorby A, Cizman B, Cobitz AR, Godoy SA, Jha V, et al. Regional variation of erythropoietin-stimulating agent hyporesponsiveness in the global daprodustat dialysis study (ASCEND-D) [abstract no: TH-OR08]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):3. [EMBASE: 633698062]
    1. Singh AK, Carroll K, Perkovic V, Solomon S, Jha V, Johansen KL, et al. Daprodustat for the treatment of anemia in patients undergoing dialysis. New England Journal of Medicine 2021;385(25):2325-35. [MEDLINE: ] - PubMed
ASCEND‐ID 2021 {published data only}
    1. Singh AK. Daprodustat is noninferior to darbepoetin alfa in treating anemia in incident dialysis patients [abstract no: PO0465]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):184-5. [EMBASE: 636331207]
ASCEND‐ND 2021 {published data only}
    1. Perkovic V, Blackorby A, Cizman B, Carroll K, Cobitz A, Davies R, et al. ASCEND-ND: Study design and baseline characteristics. Nephrology Dialysis Transplantation 2021;36(Suppl 1):i334-5. [EMBASE: 635918331]
    1. Singh AK, Carroll K, McMurray JJ, Solomon S, Jha V, Johansen KL, et al. Daprodustat for the treatment of anemia in patients not undergoing dialysis. New England Journal of Medicine 2021;385(25):2313-24. [MEDLINE: ] - PubMed
ASCEND‐NHQ 2021 {published data only}
    1. Johansen KL, Cobitz AR, Lopes RD, Singh AK, Obrador GT, Cizman B, et al. Effects of daprodustat on hemoglobin and quality of life in patients with CKD: results of the ascend-NHQ randomized, double-blind, placebo-controlled trial [abstract no: FR-OR53]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):36. [EMBASE: 636330656]
ASCEND‐TD 2021 {published data only}
    1. Coyne DW, Singh AK, Lopes RD, Bailey CK, Dimino TL, Huang C, et al. ASCEND-TD: A randomized, double-blind, active-controlled study of daprodustat administered three times weekly in hemodialysis patients [abstract no: PO0487]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):191. [EMBASE: 636329480]
Besarab 2015 {published data only}
    1. Besarab A, Hutler HN, Klaus S, Lee TT, Lilienfeld DE, Neff TB, et al. FG-4592, a novel oral HIF prolyl hydroxylase inhibitor, elevates hemoglobin in anemic stage 3/4 CKD patients [abstract no: SA-FC416]. Journal of the American Society of Nephrology 2010;21(Abstract Suppl):95A.
    1. Besarab A, Provenzano R, Hertel J, Zabaneh R, Klaus SJ, Lee T, et al. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. Nephrology Dialysis Transplantation 2015;30(10):1665-73. [MEDLINE: ] - PMC - PubMed
Brigandi 2016 {published data only}
    1. Brigandi RA, Johnson B, Oei C, Westerman M, Olbina G, Zoysa J, et al. A novel hypoxia-inducible factor-prolyl hydroxylase inhibitor (GSK1278863) for anemia in CKD: a 28-day, phase 2a randomized trial. American Journal of Kidney Diseases 2016;67(6):861-71. [MEDLINE: ] - PubMed
    1. Brigandi RA, Johnson B, Oei C, Westerman ME, Olbina G, Kumar S, et al. Induction of erythropoiesis in anemic patients by prolylhydroxylase inhibitor in a repeat dose, randomized placebo controlled trial [abstract no: SA-PO117]. Journal of the American Society of Nephrology 2012;23(Abstract Suppl):662A.
    1. Brigandi RA, Westerman ME, Olbina G, Oei C, Russ SF, Kumar S. Modulation of hepcidin by prolylhydroxylase inhibitor in randomized trials [abstract no: SA-PO118]. Journal of the American Society of Nephrology 2012;23(Abstract Suppl):662A.
Chen 2019 {published data only}
    1. Chen N, Hao C, Liu B, Lin HL, Caili W, Xing CY, et al. A phase 3, randomized, open-label, active-controlled study of efficacy and safety of roxadustat for treatment of anemia in subjects with CKD on dialysis [abstract no: TH-PO1152]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):B5.
    1. Chen N, Hao C, Liu BC, Lin H, Wang C, Xing C, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. New England Journal of Medicine 2019;381(11):1011-22. [MEDLINE: ] - PubMed
Chen 2019a {published data only}
    1. Chen N, Hao C, Peng X, Lin H, Yin A, Hao L, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. New England Journal of Medicine 2019;381(11):1001-10. [MEDLINE: ] - PubMed
    1. Chen N, Hao C, Peng X, Lin HL, Yin A, Hao L, et al. A phase 3, randomized, double-blind, placebo-controlled study of efficacy and safety of roxadustat (FG-4592) for treatment of anemia in subjects with CKD not on dialysis [abstract no: TH-PO1153]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):B5.
Chen DD 2017 {published data only}
    1. Chen N, Qian J, Chen J, Yu X, Mei C, Hao C, et al. Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China. Nephrology Dialysis Transplantation 2017;32(8):1373-86. [MEDLINE: ] - PMC - PubMed
Chen NDD 2017 {published data only}
    1. Chen N, Qian J, Chen J, Yu X, Mei C, Hao C, et al. Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China. Nephrology Dialysis Transplantation 2017;32(8):1373-86. [MEDLINE: ] - PMC - PubMed
    1. Qian JQ, Chen N, Chen J, Hao C, Lin HL, Ni D, et al. A randomized, double-blind, placebo controlled trial of FG-4592 for correction of anemia in subjects with chronic kidney disease in China [abstract no: FR-OR011]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):38A.
DIALOGUE 1 2019 {published data only}
    1. Akizawa T, Macdougall IC, Berns JS, Bernhardt T, Taguchi M, Ogura E, et al. Iron regulation by molidustat, bay 85-3934, a daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor in patients with chronic kidney disease [abstract no: SP334]. Nephrology Dialysis Transplantation 2018;33(Suppl 1):i457. [EMBASE: 622606520]
    1. Akizawa T, Macdougall IC, Berns JS, Yamamoto H, Taguchi M, Iekushi K, et al. Iron regulation by molidustat, a daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor, in patients with chronic kidney disease. Nephron 2019;143(4):243-54. [MEDLINE: ] - PMC - PubMed
    1. Macdougall IC, Akizawa T, Berns J, Lentini S, Bernhardt T. Molidustat increases haemoglobin in erythropoiesis stimulating agents (ESA)-naive anaemic patients with chronic kidney disease not on dialysis (CKD-ND) [abstract no: SO036]. Nephrology Dialysis Transplantation 2016;31(Suppl 1):i16. [EMBASE: 72325954]
    1. Macdougall IC, Akizawa T, Berns JS, Bernhardt T, Krueger T. Effects of molidustat in the treatment of anemia in CKD [Erratum in: Clin J Am Soc Nephrol. 2019 Oct 7;14(10):1524]. Clinical Journal of the American Society of Nephrology: CJASN 2019;14(1):28-39. [MEDLINE: ] - PMC - PubMed
    1. Macdougall IC, Berns JS, Akizawa T, Fishbane S, Bernhardt T. DIALOGUE phase 2 program for BAY85-3934 a HIF-PH inhibitor with daily oral treatment in anemic patients suffering from CKD/ESRD [abstract no: FR-PO219]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):413A.
DIALOGUE 2 2019 {published data only}
    1. Akizawa T, Macdougall IC, Berns JS, Yamamoto H, Taguchi M, Iekushi K, et al. Iron regulation by molidustat, a daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor, in patients with chronic kidney disease. Nephron 2019;143(4):243-54. [MEDLINE: ] - PMC - PubMed
    1. Macdougall IC, Akizawa T, Berns J, Lentini S, Bernhardt T, Kruger T. Safety and efficacy of molidustat in erythropoiesis stimulating agents (ESA) pre-treated anaemic patients with chronic kidney disease not on dialysis (CKD-ND) [abstract no: SP309]. Nephrology Dialysis Transplantation 2016;31(Suppl 1):i193. [EMBASE: 72326411]
    1. Macdougall IC, Akizawa T, Berns J, Lentini S, Bernhardt T. Molidustat increases haemoglobin in erythropoiesis stimulating agents (ESA)-naive anaemic patients with chronic kidney disease not on dialysis (CKD-ND) [abstract no: SO036]]. Nephrology Dialysis Transplantation 2016;31(Suppl 1):i16. [EMBASE: 72325954]
    1. Macdougall IC, Akizawa T, Berns JS, Bernhardt T, Krueger T. Effects of molidustat in the treatment of anemia in CKD [Erratum in: Clin J Am Soc Nephrol. 2019 Oct 7;14(10):1524]. Clinical Journal of the American Society of Nephrology: CJASN 2019;14(1):28-39. [MEDLINE: ] - PMC - PubMed
    1. Macdougall IC, Berns JS, Akizawa T, Fishbane S, Bernhardt T. DIALOGUE phase 2 program for BAY85-3934 a HIF-PH inhibitor with daily oral treatment in anemic patients suffering from CKD/ESRD [abstract no: FR-PO219]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):413A.
DIALOGUE 4 2019 {published data only}
    1. Akizawa T, Macdougall IC, Berns JS, Yamamoto H, Taguchi M, Iekushi K, et al. Iron regulation by molidustat, a daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor, in patients with chronic kidney disease. Nephron 2019;143(4):243-54. [MEDLINE: ] - PMC - PubMed
    1. Macdougall IC, Akizawa T, Berns J, Lentini S, Bernhardt T. Molidustat increases haemoglobin in erythropoiesis stimulating agents (ESA)-naive anaemic patients with chronic kidney disease not on dialysis (CKD-ND) [abstract no: SO036]. Nephrology Dialysis Transplantation 2016;31(Suppl 1):i16. [EMBASE: 72325954]
    1. Macdougall IC, Akizawa T, Berns JS, Bernhardt T, Krueger T. Effects of molidustat in the treatment of anemia in CKD [Erratum in: Clin J Am Soc Nephrol. 2019 Oct 7;14(10):1524]. Clinical Journal of the American Society of Nephrology: CJASN 2019;14(1):28-39. [MEDLINE: ] - PMC - PubMed
    1. Macdougall IC, Berns JS, Akizawa T, Fishbane S, Bernhardt T. DIALOGUE phase 2 program for BAY85-3934 a HIF-PH inhibitor with daily oral treatment in anemic patients suffering from CKD/ESRD [abstract no: FR-PO219]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):413A.
DOLOMITES 2021 {published data only}
    1. Barratt J, Andric B, Tataradze A, Schoemig M, Reusch M, Valluri U, et al. Roxadustat for the treatment of anemia in CKD patients not on dialysis (NDD): a phase 3, randomized, open-label, active-controlled study [abstract no: TH-OR02]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):1. [EMBASE: 633697812]
    1. Barratt J, Andric B, Tataradze A, Schomig M, Reusch M, Valluri U, et al. Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a phase 3, randomised, open-label, active-controlled study (DOLOMITES). Nephrology Dialysis Transplantation 2021;36(9):1616-28. [MEDLINE: ] - PMC - PubMed
    1. Barratt J, Andric B, Tataradze A, Schomig M, Reusch M, Valluri U, et al. Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a phase 3, randomised, open-label, active controlled study [abstract no: MO001]. Nephrology Dialysis Transplantation 2020;35(Suppl 3):iii101. [EMBASE: 633423023] - PMC - PubMed
    1. Barratt J, Andric B, Tataradze A, Schomig M, Reusch M, Valluri U, et al. Roxadustat for the treatment of anemia in chronic kidney disease (CKD) patients not on dialysis (NDD): a phase 3, randomized, open-label, active-controlled study [abstract no: Pos-247]. Kidney International Reports 2021;6(4 Suppl):S104. [EMBASE: 2011683542]
HIMALAYAS 2021 {published data only}
    1. Provenzano M, Evgeny S, Liubov E, Korneyeva S, Kathresal AA, Poole L, et al. HIMALAYAS: a phase 3, randomized, open-label, active-controlled study of the efficacy and safety of roxadustat in the treatment of anemia in incident-dialysis patients [abstract no: TH-OR021]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):5. [EMBASE: 633771140]
    1. Provenzano R, Shutov E, Eremeeva L, Korneyeva S, Poole L, Saha G, et al. Roxadustat for anemia in patients with end-stage renal disease incident to dialysis. Nephrology Dialysis Transplantation 2021;36(9):1717-30. [MEDLINE: ] - PubMed
Holdstock 2019 {published data only}
    1. Cizman B, Ackert J, Meadowcroft A, Biswas N, Kelly D, Kleinman D, et al. Ocular safety profile of daprodustat: results of two 24 week studies [abstract no: SAO004]. Nephrology Dialysis Transplantation 2018;33(Suppl 1):i316. [EMBASE: 622604997]
    1. Holdstock L, Cizman B, Meadowcroft AM, Biswas N, Johnson BM, Jones D, et al. Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants with chronic kidney disease. Clinical Kidney Journal 2019;12(1):129-38. [MEDLINE: ] - PMC - PubMed
    1. Holdstock L, Cizman B, Meadowcroft AM, Biswas N, Jones D, Johnson BM, et al. Daprodustat, a HIF-prolyl-hydroxylase inhibitor, increases and maintains hemoglobin over 24 weeks in anemic chronic kidney disease subjects [abstract no: TH-PO908]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):304A.
Holdstock 2019a {published data only}
    1. Cizman B, Ackert J, Meadowcroft A, Biswas N, Kelly D, Kleinman D, et al. Ocular safety profile of daprodustat: results of two 24 week studies [abstract no: SAO004]. Nephrology Dialysis Transplantation 2018;33(Suppl 1):i316. [EMBASE: 622604997]
    1. Holdstock L, Cizman B, Meadowcroft AM, Biswas N, Johnson BM, Jones D, et al. Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants with chronic kidney disease. Clinical Kidney Journal 2019;12(1):129-38. [MEDLINE: ] - PMC - PubMed
    1. Holdstock L, Cizman B, Meadowcroft AM, Biswas N, Jones D, Johnson BM, et al. Daprodustat, a HIF-prolyl-hydroxylase inhibitor, increases and maintains hemoglobin over 24 weeks in anemic chronic kidney disease subjects [abstract no: TH-PO908]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):304A.
Hou 2021 {published data only}
    1. Hou YP, Mao XY, Wang C, Xu ZH, Bu ZH, Xu M, et al. Roxadustat treatment for anemia in peritoneal dialysis patients: a randomized controlled trial. Journal of the Formosan Medical Association 2021;121(2):529-38. [MEDLINE: ] - PubMed
INNO2VATE 2020 {published data only}
    1. Chertow GM, Boudville N, Chowdhury P, Gonzalez C, Kooienga L, Luo W, et al. Vadadustat for treatment of anemia in patients with dialysis-dependent CKD receiving peritoneal dialysis [abstract no: PO0464]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):184. [EMBASE: 636331136]
    1. Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, et al. Safety and efficacy of vadadustat for anemia in patients undergoing dialysis. New England Journal of Medicine 2021;384(17):1601-12. [MEDLINE: ] - PubMed
    1. Eckardt KU, Agarwal R, Farag YM, Jardine AG, Khawaja Z, Koury MJ, et al. Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials. Nephrology Dialysis Transplantation 2020;36(11):2039-48. [MEDLINE: ] - PMC - PubMed
    1. Eckardt KU. Global phase 3 clinical trials of vadadustat vs. darbepoetin alfa for treatment of anemia in patients with dialysis-dependent CKD [abstract no: TH-OR01]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):1. [EMBASE: 633697781]
    1. Parfrey PS, Luo W, Maroni B, Anders R, Vargo D, McCullough PA. Thromboembolic events with vadadustat vs. darbepoetin alfa for anemia treatment in patients with dialysis-dependent CKD [abstract no: PO0463]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):184. [EMBASE: 636331080]
INNO2VATE 2020a {published data only}
    1. Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, et al. Safety and efficacy of vadadustat for anemia in patients undergoing dialysis. New England Journal of Medicine 2021;384(17):1601-12. [MEDLINE: ] - PubMed
    1. Eckardt KU, Agarwal R, Farag YM, Jardine AG, Khawaja Z, Koury MJ, et al. Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials. Nephrology Dialysis Transplantation 2020;36(11):2039-48. [MEDLINE: ] - PMC - PubMed
    1. Eckardt KU. Global phase 3 clinical trials of vadadustat vs. darbepoetin alfa for treatment of anemia in patients with dialysis-dependent CKD [abstract no: TH-OR01]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):1. [EMBASE: 633697781]
    1. Winkelmayer WC, Fishbane S, Tumlin JA, Farag YM, Luo W, Anders R, et al. Iron-related outcomes in patients with dialysis-dependent CKD randomized to vadadustat vs. darbepoetin alfa [abstract no: PO0457]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):182. [EMBASE: 636330773]
Meadowcroft 2019 {published data only}
    1. Cizman B, Ackert J, Meadowcroft A, Biswas N, Kelly D, Kleinman D, et al. Ocular safety profile of daprodustat: results of two 24 week studies [abstract no: SAO004]. Nephrology Dialysis Transplantation 2018;33(Suppl 1):i316. [EMBASE: 622604997]
    1. Cobitz AR, Meadowcroft AM, Cizman B, Holdstock L, Biswas N, Jones D, et al. Daprodustat, a HIF-prolyl-hydroxylase inhibitor, maintains hemoglobin levels over 24 weeks in anemic hemodialysis subjects switching from recombinant human erythropoietin. [abstract no: SA-OR114]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):93A.
    1. Meadowcroft AM, Cizman B, Holdstock L, Biswas N, Johnson BM, Jones D, et al. Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants on hemodialysis. Clinical Kidney Journal 2019;12(1):139-48. [MEDLINE: ] - PMC - PubMed
MIYABI HD‐M 2019 {published data only}
    1. Akizawa T, Taguchi M, Matsuda Y, Iekushi K, Yamada T, Yamamoto H. Molidustat for the treatment of renal anaemia in patients with dialysis-dependent chronic kidney disease: Design and rationale of three phase III studies. BMJ Open 2019;9(6):e026602. [MEDLINE: ] - PMC - PubMed
    1. Akizawa T, Yamada T, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, et al. Molidustat for Japanese patients with renal anemia receiving dialysis. Kidney International Reports 2021;6(10):2604–16. [MEDLINE: ] - PMC - PubMed
    1. Akizawa T, Yamada T, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, et al. Results from a phase 3 study comparing the efficacy and safety of molidustat vs. Darbepoetin Alfa in patients receiving hemodialysis and treated with erythropoiesis-stimulating agents (ESAS) [abstract no: PO22623]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):B4. [EMBASE: 633697376]
MIYABI ND‐C 2019 {published data only}
    1. Yamamoto H, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, Akizawa T. Efficacy and safety of molidustat for anemia in ESA-naive nondialysis patients: a randomized, phase 3 trial. American Journal of Nephrology 2021;52(10-11):871-83. [MEDLINE: ] - PubMed
    1. Yamamoto H, Taguchi M, Matsuda Y, Iekushi K, Yamada T, Akizawa T. Molidustat for the treatment of renal anaemia in patients with non-dialysis-dependent chronic kidney disease: design and rationale of two phase III studies. BMJ Open 2019;9(6):e026704. [MEDLINE: ] - PMC - PubMed
    1. Yamamoto H, Taguchi M, Nobori K, Matsuda Y, Iekushi K, Akizawa T. To investigate the efficacy and safety of molidustat in non-dialysis patients with renal anemia who are not treated with erythropoiesis stimulating agents: MIYABI ND-C [abstract no: P1866]. Nephrology Dialysis Transplantation 2020;35(Suppl 3):iii2177. [EMBASE: 633422996]
MIYABI ND‐M 2019 {published data only}
    1. Yamamoto H, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, Akizawa T. Molidustat for renal anemia in nondialysis patients previously treated with erythropoiesis-stimulating agents: a randomized, open-label, phase 3 study. American Journal of Nephrology 2021;52(10-11):884-93. [MEDLINE: ] - PubMed
    1. Yamamoto H, Taguchi M, Matsuda Y, Iekushi K, Yamada T, Akizawa T. Molidustat for the treatment of renal anaemia in patients with non-dialysis-dependent chronic kidney disease: design and rationale of two phase III studies. BMJ Open 2019;9(6):e026704. [MEDLINE: ] - PMC - PubMed
    1. Yamamoto H, Taguchi M, Nobori K, Matsuda Y, Iekushi K, Akizawa T. To investigate the efficacy and safety of molidustat in non-dialysis patients with renal anemia who are treated with erythropoiesis stimulating agents: Miyabi ND-M [Abstract no: P1868]. Nephrology Dialysis Transplantation 2020;35(Suppl 3):iii2179. [EMBASE: 633423006]
Nangaku 2021 {published data only}
    1. Nangaku M, Kondo K, Ueta K, Kokado Y, Kaneko G, Matsuda H, et al. Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a phase 3, multicenter, randomized, double-blind study. Nephrology Dialysis Transplantation 2021;36(9):1731-41. [MEDLINE: ] - PMC - PubMed
    1. Nangaku M, Kondo K, Ueta K, Kokado Y, Kaneko G, Matsuda H, et al. Randomized, double-blinded, active-controlled (darbepoetin alfa), phase 3 study of vadadustat in CKD patients with anemia on hemodialysis in Japan [abstract no: TH-OR024]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):6. [EMBASE: 633771357]
Nangaku 2021a {published data only}
    1. Nangaku M, Kondo K, Kokado Y, Ueta K, Kaneko G, Shiosaka M, et al. Randomized, open-label, active-controlled (darbepoetin alfa), phase 3 study of vadadustat for treating anemia in non-dialysis-dependent CKD patients in Japan [abstract no: SA-PO229]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):823. [EMBASE: 633767995]
    1. Nangaku M, Kondo K, Kokado Y, Ueta K, Kaneko G, Tandai T, et al. Phase 3 randomized study comparing vadadustat with darbepoetin alfa for anemia in Japanese patients with nondialysis-dependent CKD. Journal of the American Society of Nephrology 2021;32(7):1779-90. [MEDLINE: ] - PMC - PubMed
Nangaku 2021b {published data only}
    1. GSK201753. A 52-week, Phase III, open-label, multi-center study to evaluate efficacy and safety of GSK1278863 in Japanese non-dialysis and peritoneal dialysis subjects with anemia associated with chronic kidney disease [study protocol]. www.clinicaltrials.gov/ProvidedDocs/63/NCT02791763/Prot_000.pdf (accessed 9 May 2022).
    1. Nangaku M, Hamano T, Akizawa T, Tsubakihara Y, Nagai R, Okuda N, et al. Daprodustat compared with epoetin beta pegol for anemia in Japanese patients not on dialysis: a 52-week randomized open-label phase 3 trial. American Journal of Nephrology 2021;52(1):26-35. [MEDLINE: ] - PMC - PubMed
NCT01888445 {published data only}
    1. Astellas1517-CL-0304. A study to investigate the effect of ASP1517 after intermittent oral dosing in dialysis chronic kidney disease patients with anemia compared with darbepoetin as a reference drug [A Japanese, phase 2, multicenter, randomized, 4-arm parallel, double-blind (arms 1-3), open-label (arm 4), active-comparator (darbepoetin alfa) study of intermittent oral dosing of asp1517 in hemodialysis-dependent chronic kidney disease patients with anemia [1517-CL-0304 clinical study results report]]. www.trialsummaries.com/Study/StudyDetails?id=14175&tenant=MT_AST_9011; www.clinicaltrials.gov/ct2/show/NCT01888445 (first received 6 August 2018).
NDD‐CKD 2020 {published data only}
    1. Nangaku M, Farag YM, deGoma E, Luo W, Vargo D, Khawaja Z. Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in Japanese patients. Nephrology Dialysis Transplantation 2020 Jul 20 [epub ahead of print]. [DOI: 10.1093/ndt/gfaa060] [MEDLINE: ] - DOI - PubMed
    1. Nangaku M, Khawaja Z, Luo W, Garafola S, De Goma E, Komatsu Y. Randomized, placebo-controlled phase 2 trials of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), to treat anemia of CKD [abstract no: TH-PO228]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):171. [EMBASE: 633737146]
    1. Solinsky C, Farag YM, Khawaja Z, Anders R, Luo W, Chavan A, et al. Impact of vadadustat on iron regulation in Japanese subjects with chronic kidney disease (CKD) [abstract no: 352]. American Journal of Kidney Diseases 2020;75(4):638-9. [EMBASE: 2005716872]
NDD‐CKD 2020a {published data only}
    1. Nangaku M, Farag YM, deGoma E, Luo W, Vargo D, Khawaja Z. Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in Japanese patients. Nephrology Dialysis Transplantation 2020 Jul 20 [epub ahead of print]. [DOI: 10.1093/ndt/gfaa060] [MEDLINE: ] - DOI - PubMed
    1. Nangaku M, Khawaja Z, Luo W, Garafola S, deGoma E, Komatsu Y. Randomized, placebo-controlled phase 2 trials of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), to treat anemia of CKD [abstract no: TH-PO228]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):171. [EMBASE: 633737146]
    1. Solinsky C, Farag YM, Khawaja Z, Anders R, Luo W, Chavan A, et al. Impact of vadadustat on iron regulation in Japanese subjects with chronic kidney disease (CKD) [abstract no: 352]. American Journal of Kidney Diseases 2020;75(4):638-9. [EMBASE: 2005716872]
OLYMPUS 2021 {published data only}
    1. AstraZeneca. A phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis [clinical study protocol V6; 31 August 2018]. www.clinicaltrials.gov/ProvidedDocs/27/NCT02174627/Prot_000.pdf (accessed 9 May 2022).
    1. Eleftheriadis T, Pissas G, Liakopoulos V, Stefanidis I. On the increased event rate of urinary tract infection and pneumonia in CKD patients treated with roxadustat for anemia. Journal of the American Society of Nephrology 2021;32(6):1537. [MEDLINE: ] - PMC - PubMed
    1. Fishbane S, El-Shahawy MA, Pecoits-Filho R, Van BP, Houser MT, Frison L, et al. OLYMPUS: a phase 3, randomized, double-blind, placebo-controlled, international study of roxadustat efficacy in patients with non-dialysis-dependent (NDD) CKD and anemia [abstract no: TH-OR023]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):6. [EMBASE: 633771285]
    1. Fishbane S, El-Shahawy MA, Pecoits-Filho R, Van BP, Houser MT, Frison L, et al. Roxadustat for treating anemia in patients with CKD not on dialysis: results from a randomized phase 3 study. Journal of the American Society of Nephrology 2021;32(3):737-55. [MEDLINE: ] - PMC - PubMed
    1. Fishbane S, El-Shahawy MA, Van BP, Little DJ. Authors' Reply. Journal of the American Society of Nephrology 2021;32(6):1537-8. [MEDLINE: ] - PMC - PubMed
Pergola 2016 {published data only}
    1. Haase VH, Spinowitz BS, Pergola PE, Farmer T, Maroni BJ, Hartman CS. AKB-6548 demonstrates controlled hemogloblin (HGB) response in a phase 2b study for the treatment of anemia in patients with chronic kidney disease not on dialysis (ND-CKD) [abstract no: TH-PO649]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):237A.
    1. Haase VH, Spinowitz BS, Pergola PE, Khawaja Z, Chan J, Zuraw Q, et al. Efficacy and dose requirements of vadadustat are independent of systemic inflammation and prior erythropoiesis-stimulating agent(ESA) dose in patients with non-dialysis dependent chronic kidney disease (NDD-CKD) [abstract no: TH-PO907]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):304A.
    1. Pergola PE, Spinowitz B, Haase VH, Hartman CS, Farmer TM, Polu KR, et al. AKB-6548, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI) for the treatment of anemia in patients with chronic kidney disease not on dialysis (ND-CKD) [abstract no: FO015]. Nephrology Dialysis Transplantation 2015;30(Suppl 3):iii8. [EMBASE: 72206296]
    1. Pergola PE, Spinowitz BS, Hartman CS, Maroni BJ, Haase VH. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Kidney International 2016;90(5):1115-22. [MEDLINE: ] - PubMed
    1. Spinowitz BS, Pergola PE, Haase VH, Farmer TM, Hartman CS, Maroni BJ. Hemoglobin (HGB) response in a phase 2b study of AKB-6548 for the treatment of anemia in patients with non-dialysis dependant chronic kidney disease (NDD-CKD). [abstract no: TH-OR038]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):11A.
PRO2TECT‐CONVERSION 2021 {published data only}
    1. Bunn HF. Vadadustat for anemia in patients with dialysis-dependent or non-dialysis-dependent chronic kidney disease. New England Journal of Medicine 2021;385(16):e56. [MEDLINE: ] - PubMed
    1. Chertow GM, Pergola PE, Agarwal R, Block GA, Farag YM, Jardine AG, et al. Cardiovascular safety and efficacy of vadadustat for the treatment of anemia in non-dialysis-dependent CKD: design and baseline characteristics. American Heart Journal 2021;235(5):1-11. [MEDLINE: ] - PubMed
    1. Chertow GM, Pergola PE, Farag YM, Agarwal R, Arnold S, Bako G, et al. Vadadustat in patients with anemia and non-dialysis-dependent CKD. New England Journal of Medicine 2021;384(17):1589-600. [MEDLINE: ] - PubMed
    1. Chertow GM. Global phase 3 clinical trials of vadadustat vs. darbepoetin alfa for treatment of anemia in patients with non-dialysis-dependent CKD [abstract no: FR-OR54]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):B2. [EMBASE: 633697273]
    1. Koury M, Pergola PE, Roy-Chaudhury P, Farag YM, Luo W, Anders R, et al. Iron-related outcomes in patients with non-dialysis-dependent CKD randomized to vadadustat vs. darbepoetin Alfa [abstract no: PO0482]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):190. [EMBASE: 636329134]
PRO2TECT‐CORRECTION 2021 {published data only}
    1. Bunn HF. Vadadustat for anemia in patients with dialysis-dependent or non-dialysis-dependent chronic kidney disease. New England Journal of Medicine 2021;385(16):e56. [MEDLINE: ] - PubMed
    1. Chertow GM, Pergola PE, Agarwal R, Block GA, Farag YM, Jardine AG, et al. Cardiovascular safety and efficacy of vadadustat for the treatment of anemia in non-dialysis-dependent CKD: design and baseline characteristics. American Heart Journal 2021;235(5):1-11. [MEDLINE: ] - PubMed
    1. Chertow GM, Pergola PE, Farag YM, Agarwal R, Arnold S, Bako G, et al. Vadadustat in patients with anemia and non-dialysis-dependent CKD. New England Journal of Medicine 2021;384(17):1589-600. [MEDLINE: ] - PubMed
    1. Chertow GM. Global phase 3 clinical trials of vadadustat vs. darbepoetin alfa for treatment of anemia in patients with non-dialysis-dependent CKD [abstract no: FR-OR5]. Journal of the American Society of Nephrology 2020;31(Abstract Suppl):B2. [EMBASE: 633697273]
    1. Koury M, Pergola PE, Roy-Chaudhury P, Farag YM, Luo W, Anders R, et al. Iron-related outcomes in patients with non-dialysis-dependent CKD randomized to vadadustat vs. darbepoetin alfa [abstract no: PO0482]. Journal of the American Society of Nephrology 2021;32(Abstract Suppl):190. [EMBASE: 636329134]
Provenzano 2008 {published data only}
    1. Provenzano R, Fadda G, Bernardo M, James C, Kochendoerfer G, Lee T, et al. FG2216, a novel oral HIF-PHI, stimulates erythropoiesis and increases hemoglobin concentration in patients with non-dialysis CKD [abstract no: 212]. American Journal of Kidney Diseases 2008;51(4):A80.
    1. Provenzano R, Hulter H, Agarwal A, Klaus S, Lee T, Yu P, et al. Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor FG-2216 increases Hb without FE depletion in the absence of IV Fe [abstract no: 249]. American Journal of Kidney Diseases 2013;61(4):A78. [EMBASE: 71024073]
Provenzano 2016 {published data only}
    1. Provenzano R, Besarab A, Dua SL, Nguyen PV, Wright SH, Zeig S, et al. FG-4592, a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), maintains hemoglobin levels and lowers cholesterol in hemodialysis patients: phase 2 comparison with epoetin alfa [abstract no: FR-PO257]. Journal of the American Society of Nephrology 2012;23(Abstract Suppl):428A.
    1. Provenzano R, Besarab A, Wright S, Dua S, Zeig S, Nguyen P, et al. Roxadustat (FG-4592) versus epoetin alfa for anemia in patients receiving maintenance hemodialysis: a phase 2, randomized, 6- to 19-week, open-label, active-comparator, dose-ranging, safety and exploratory efficacy study. American Journal of Kidney Diseases 2016;67(6):912-24. [MEDLINE: ] - PubMed
Provenzano 2016a {published data only}
    1. Provenzano R, Besarab A, Dua SL, Nguyen PV, Wright SH, Zeig S, et al. FG-4592, a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), maintains hemoglobin levels and lowers cholesterol in hemodialysis patients: phase 2 comparison with epoetin alfa [abstract no: FR-PO257]. Journal of the American Society of Nephrology 2012;23(Abstract Suppl):428A.
    1. Provenzano R, Besarab A, Wright S, Dua S, Zeig S, Nguyen P, et al. Roxadustat (FG-4592) versus epoetin alfa for anemia in patients receiving maintenance hemodialysis: a phase 2, randomized, 6- to 19-week, open-label, active-comparator, dose-ranging, safety and exploratory efficacy study. American Journal of Kidney Diseases 2016;67(6):912-24. [MEDLINE: ] - PubMed
PYRENEES 2021 {published data only}
    1. Astellas 1517-CL-0613. Roxadustat in the treatment of anemia in end stage renal disease (ESRD) patients on stable dialysis [A phase 3, randomized, open-label, active-controlled study to evaluate the efficacy and safety of roxadustat in the maintenance treatment of anemia in end stage renal disease patients on stable dialysis]. www.trialsummaries.com/Study/StudyDetails?id=14380&tenant=MT_AST_9011 (accessed 9 May 2022).
    1. Csiky B, Schomig M, Esposito C, Barratt J, Reusch M, Valluri U, et al. Roxadustat for the maintenance treatment of anemia in patients with end-stage kidney disease on stable dialysis: a European phase 3, randomized, open-label, active-controlled study (PYRENEES). Advances in Therapy 2021;38(10):5361-80. [MEDLINE: ] - PMC - PubMed
    1. Esposito C, Csiky B, Tataradze A, Reusch M, Han C, Sulowicz W. Two phase 3, multicenter, randomized studies of intermittent oral roxadustat in anemic CKD patients on (PYRENEES) and not on (ALPS) dialysis. Swiss Medical Weekly 2020;150(Suppl 248):21-2S. [EMBASE: 634241523]
    1. Esposito C, Csiky B, Tataradze A, Reusch M, Han C, Sulowicz W. Two phase 3, multicenter, randomized studies of intermittent oral roxadustat in anemic CKD patients on (PYRENEES) and not on (ALPS) dialysis [abstract no: SA-PO225]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):822. [EMBASE: 633767739]
ROCKIES 2019 {published data only}
    1. AstraZeneca. A phase 3, multicenter, randomized, open-label, active-controlled study of the safety and efficacy of roxadustat in the treatment of anemia in dialysis patients [Clinical study protocol v8.0 19 September 2018]. www.clinicaltrials.gov/ProvidedDocs/31/NCT02174731/Prot_000.pdf (accessed 10 May 2022).
    1. Fishbane S, Pollock CA, El-Shahawy MA, Escudero ET, Rastogi A, Van BP, et al. ROCKIES: an international, phase 3, randomized, open-label, active-controlled study of roxadustat for anemia in dialysis-dependent CKD patients [abstract no: TH-OR022]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):6. [EMBASE: 633771219]
SIERRAS 2021 {published data only}
    1. Charytan C, Manllo-Karim R, Martin ER, Steer D, Bernardo M, Dua SL, et al. A randomized trial of roxadustat in anemia of kidney failure: SIERRAS study. Kidney International Reports 2021;6(7):1829-39. [MEDLINE: ] - PMC - PubMed
    1. Charytan C, Manllo-Karim R, Martin ER, Steer D, Bernardo M, Dua SL, et al. SIERRAS: A phase 3, open-label, randomized, active-controlled study of the efficacy and safety of roxadustat in the maintenance treatment of anemia in subjects with ESRD on stable dialysis [abstract no: SA-PO227]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):822. [EMBASE: 633767862]
SYMPHONY HD 2021 {published data only}
    1. Akizawa T, Maeda K, Miyazawa Y, Koretomo R. Phase 3 study to compare the efficacy and safety of enarodustat (JTZ-951), an oral HIF-PH inhibitor, with darbepoetin alfa in anemic patients with CKD receiving maintenance hemodialysis [abstract no: TH-PO1186]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):B4.
    1. Akizawa T, Nangaku M, Yamaguchi T, Koretomo R, Maeda K, Miyazawa Y, et al. A phase 3 study of enarodustat (JTZ-951) in Japanese hemodialysis patients for treatment of anemia in chronic kidney disease: SYMPHONY HD study. Kidney Diseases 2021;7(6):494-502. [EMBASE: 2013576033] - PMC - PubMed
SYMPHONY ND 2021 {published data only}
    1. Akizawa T, Nangaku M, Yamaguchi T, Koretomo R, Maeda K, Miyazawa Y, et al. A phase 3 study of enarodustat in anemic patients with CKD not requiring dialysis: the SYMPHONY ND study. Kidney International Reports 2021;6(7):1840-9. [MEDLINE: ] - PMC - PubMed

References to studies excluded from this review

Akizawa 2015a {published data only}
    1. Akizawa T, Hanaki K, Arai M. JTZ-951, an oral novel HIF-PHD inhibitor, elevates hemoglobin in Japanese anemic patients with chronic kidney disease receiving maintenance hemodialysis [abstract no: FO019]. Nephrology Dialysis Transplantation 2015;30(Suppl 3):iii10. [EMBASE: 72206300]
Akizawa 2019a {published data only}
    1. Akizawa T, Miyazawa Y, Matsui A, Koretomo R, Arai M. Enarodustat (JTZ-951) , an oral HIF-PH inhibitor, elevates and maintains hemoglobin levels over 30 weeks in Japanese anemic patients with CKD not on dialysis [abstract no: TH-PO225]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):171. [EMBASE: 633737010]
    1. Akizawa T, Nangaku M, Yamaguchi T, Arai M, Koretomo R, Matsui A, et al. A placebo-controlled, randomized trial of enarodustat in patients with chronic kidney disease followed by long-term trial. American Journal of Nephrology 2019;49(2):165-74. [MEDLINE: ] - PMC - PubMed
Akizawa 2019b {published data only}
    1. Akizawa T, Miyazawa Y, Maeda K, Koretomo R, Arai M. Enarodustat (JTZ-951), an oral HIF-PH inhibitor, maintains hemoglobin levels switching from ESAs over 30 weeks in Japanese anemic patients with CKD receiving maintenance hemodialysis [abstract no: TH-PO226]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):171. [EMBASE: 633737068]
    1. Akizawa T, Nangaku M, Yamaguchi T, Arai M, Koretomo R, Maeda K, et al. Enarodustat, conversion and maintenance therapy for anemia in hemodialysis patients: a randomized, placebo-controlled phase 2b trial followed by long-term trial. Nephron 2019;143(2):77-85. [MEDLINE: ] - PMC - PubMed
Akizawa 2020 {published data only}
    1. Akizawa T, Otsuka T, Reusch M, Ueno M. Intermittent oral dosing of roxadustat in peritoneal dialysis chronic kidney disease patients with anemia: a randomized, phase 3, multicenter, open-label study. Therapeutic Apheresis & Dialysis 2020;24(2):115-25. [MEDLINE: ] - PMC - PubMed
    1. Akizawa T, Otsuka T, Reusch M, Ueno M. Phase 3, multicenter, open-label study of intermittent oral roxadustat in peritoneal dialysis CKD patients with anemia [abstract no: SA-OR075]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):99. [EMBASE: 633736837]
Akizawa 2020b {published data only}
    1. Akizawa T, Otsuka T, Yamaguchi Y, Reusch M. Phase 3, multicenter, randomized, open-label, non-comparative study of intermittent oral roxadustat in ESA-naive CKD patients not on dialysis in Japan [abstract no: SA-PO226]. Journal of the American Society of Nephrology 2019;30(Abstract Suppl):822. [EMBASE: 633767826]
    1. Akizawa T, Yamaguchi Y, Otsuka T, Reusch M. A phase 3, multicenter, randomized, two-arm, open-label study of intermittent oral dosing of roxadustat for the treatment of anemia in Japanese erythropoiesis-stimulating agent-naive chronic kidney disease patients not on dialysis. Nephron 2020;144(8):372-82. [MEDLINE: ] - PMC - PubMed
Akizawa 2020g {published data only}
    1. Akizawa T, Ueno M, Shiga T, Reusch M. Oral roxadustat three times weekly in ESA-naive and ESA-converted patients with anemia of chronic kidney disease on hemodialysis: Results from two phase 3 studies. Therapeutic Apheresis & Dialysis 2020;24(6):628-41. [MEDLINE: ] - PMC - PubMed
ASCEND:Fe 2018 {published data only}
    1. NCT03457701. Anemia studies in CKD: erythropoiesis via a novel prolyl hydroxylase inhibitor (PHI) daprodustat- iron (ASCEND: Fe) [A repeat dose, open label, two period, randomized, cross over study to compare the effect of daprodustat to recombinant, human erythropoietin (rhEPO) on oral iron absorption in adult participants with anemia associated with chronic kidney disease who are not on dialysis]. www.clinicaltrials.gov/show/NCT03457701 (first received 7 March 2018).
ASCEND‐BP 2017 {published data only}
    1. NCT03029247. Anemia study in chronic kidney disease (CKD): erythropoiesis via a novel prolyl hydroxylase inhibitor (PHI) daprodustat-blood pressure (ASCEND-BP) [A randomized, open-label study to evaluate the effect of daprodustat on blood pressure in subjects with anemia associated with chronic kidney disease on hemodialysis switched from a stable dose of an erythropoiesis-stimulating agent]. www.clinicaltrials.gov/show/NCT03029247 (first received 24 January 2017).
Bailey 2019 {published data only}
    1. Bailey CK, Caltabiano S, Cobitz AR, Huang C, Mahar KM, Patel V, et al. A 29-day safety, efficacy, and pharmacodynamic study of a hypoxia-inducible factor prolyl hydroxylase inhibitor, daprodustat, administered TIW in anemic subjects on hemodialysis (HD) [abstract no: SA-PO811]. Journal of the American Society of Nephrology 2017;28(Abstract Suppl):889. [EMBASE: 633698132]
    1. Bailey CK, Caltabiano S, Cobitz AR, Huang C, Mahar KM, Patel VV. A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis. BMC Nephrology 2019;20(1):372. [MEDLINE: ] - PMC - PubMed
Besarab 2016 {published data only}
    1. Besarab A, Chan DT, Dua SL, Franco M, Henry E, Leong R, et al. Hypoxia inducing factor prolyl hydroxylase inhibitor FG-4592 corrects anemia in peritoneal dialysis [abstract no: SA-OR087]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):91A.
    1. Besarab A, Chernyavskaya E, Motylev I, Shutov E, Kumbar LM, Gurevich K, et al. Roxadustat (FG-4592): correction of anemia in incident dialysis patients. Journal of the American Society of Nephrology 2016;27(4):1225-33. [MEDLINE: ] - PMC - PubMed
    1. Besarab A, Chernyavskaya EN, Motylev I, Evgeny S, Yampolskiy AF, Kumbar LM, et al. FG-4592, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, corrects anemia without iron supplementation in incident dialysis patients [abstract no: TH-OR096]. Journal of the American Society of Nephrology 2012;23(Abstract Suppl):21A.
    1. Besarab A, Szczech L, Yu KH, Neff TB. Impact of iron regimen on iron indices and hepcidin during roxadustat anemia correction in incident dialysis patients [abstract no: TH-PO847]. Journal of the American Society of Nephrology 2014;25(Abstract Suppl):304a.
Buch 2014 {published data only}
    1. Buch A, Farmer TM, Hartman C, Alcorn H, Shalwitz R. Hemodialysis has minimal impact on the pharmacokinetics of AKB-6548, a once-daily oral inhibitor of hypoxia inducible factor prolyl-hydroxylases (HIFPHs) for the treatment of anemia related to chronic kidney disease (CKD) [abstract no: FR-PO952]. Journal of the American Society of Nephrology 2014;25(Abstract Suppl):590A.
DD‐CKD 2020 {published data only}
    1. Nangaku M, Farag YM, deGoma E, Luo W, Vargo D, Khawaja Z. Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in Japanese patients. Nephrology Dialysis Transplantation 2020 Jul 28 [epub ahead of print]. [MEDLINE: ] - PubMed
    1. Nangaku M, Khawaja Z, Luo W, Garafola S, deGoma E, Komatsu Y. Randomized, placebo-controlled phase 2 trials of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), to treat anemia of CKD [abstract no: TH-PO228]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):171. [EMBASE: 633737146]
    1. Solinsky C, Farag YM, Khawaja Z, Anders R, Luo W, Chavan A, et al. Impact of vadadustat on iron regulation in Japanese subjects with chronic kidney disease (CKD) [abstract no: 352]. American Journal of Kidney Diseases 2020;75(4):638-9. [EMBASE: 2005716872]
EudraCT2012‐004049‐34 {published data only}
    1. 2012-004049-34. A four-week, phase IIa, randomized, active-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from a stable dose of recombinant human erythropoietin to GSK1278863 in hemodialysis-dependent subjects with anaemia associated with chronic kidney disease - 4 week switch study in HD subjects. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... 2013.
    1. GSK116582. A 4 week phase IIa, randomized, active-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from a stable dose of recombinant human erythropoietin to GSK1278863 in hemodialysis-dependent subjects with anemia associated with chronic kidney disease. www.clinicaltrialsregister.eu/ctr-search/trial/2012-004049-34/results 2013.
EudraCT2012‐004050‐29 {published data only}
    1. GSK116581. A four-week phase IIa, randomized, double-blind, placebo controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of GSK1278863 in subjects with anemia associated with chronic kidney disease who are not taking recombinant human erythropoietin and are not undergoing dialysis. www.clinicaltrialsregister.eu/ctr-search/trial/2012-004050-29/results 2012.
EudraCT2015‐004790‐32 {published data only}
    1. 2015-004790-32. A 29-day, randomized, double-blinded, placebo-controlled, parallel-group, multi-center study to evaluate the efficacy, safety and pharmacokinetics of three-times weekly dosing of GSK1278863 in hemodialysis-dependent subjects with anemia associated with chronic kidney disease who are switched from a stable dose of an erythropoiesis-stimulating agent. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... 2016 Jan 13.
Frohna 2007 {published data only}
    1. Frohna PA, Milwee S, Pinkett J, Lee T, Moore-Perry K, Chou J, et al. Preliminary results from a randomized, single-blind, placebo-controlled trial of FG-4592, a novel hypoxia inducible factor prolyl hydroxylase inhibitor, in CKD anemia [abstract no: SU-PO806]. Journal of the American Society of Nephrology 2007;18(Abstracts Issue):763A.
Haase 2016 {published data only}
    1. Haase VH, Khawaja Z, Chan J, Zuraw Q, Farzaneh-Far R, Maroni BJ, et al. Vadadustat maintains hemoglobin (Hb) levels in dialysis-dependent chronic kidney disease (DD-CKD) patients independent of systemic inflammation or prior dose of erythropoiesis-stimulating agent (ESA) [abstract no: TH-PO960]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):318A.
Hartman 2014 {published data only}
    1. Hartman CS, Shalwitz IR, Shalwitz RA. Controlled hemoglobin response in a double-blind, placebo-controlled trial of AKB-6548 in subjects with chronic kidney disease [abstract no: SO051]. Nephrology Dialysis Transplantation 2014;29(Suppl 3):iii22. [EMBASE: 71491516]
    1. Shalwitz R, Hartman C, Flinn C, Shalwitz I, Peters KG, Besarab A, et al. AKB-6548, a new hypoxia-inducible factor prolyl hydroxylase inhibitor, increases hemoglobin in chronic kidney disease patients without increasing basal erythropoietin levels [abstract no: FR-OR116]. Journal of the American Society of Nephrology 2012;23(Abstract Suppl):56A.
Holdstock CKD 2016 {published data only}
    1. Holdstock L, Meadowcroft AM, Maier R, Johnson BM, Jones D, Rastogi A, et al. Four-week studies of oral hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 for treatment of anemia. Journal of the American Society of Nephrology 2016;27(4):1234-44. [MEDLINE: ] - PMC - PubMed
Holdstock HD 2016 {published data only}
    1. Holdstock L, Meadowcroft AM, Maier R, Johnson BM, Jones D, Rastogi A, et al. Four-week studies of oral hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 for treatment of anemia. Journal of the American Society of Nephrology 2016;27(4):1234-44. [MEDLINE: ] - PMC - PubMed
    1. Meadowcroft AM, Holdstock L, Maier R, Jones D, Johnson B, Cobitz AR, et al. Four-week safety, efficacy and pharmacodynamic study of hypoxia-inducible factor (HIF)-prolyl inhibitor GSK1278863 in anemic hemodialysis subjects switching from recombinant human erythropoietin [abstract no: SA-PO1092]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):6B.
Martin 2017 {published data only}
    1. Martin ER, Smith MT, Maroni BJ, Zuraw QC, deGoma EM. Clinical trial of vadadustat in patients with anemia secondary to stage 3 or 4 chronic kidney disease. American Journal of Nephrology 2017;45(5):380-8. [MEDLINE: ] - PMC - PubMed
NCT01679587 {published data only}
    1. NCT01679587. Dose escalation study to investigate safety, tolerability, pharmacodynamics, and pharmacokinetics of BAY85-3934 in subjects with chronic kidney disease (CKD) [A multicenter, randomized, single-blind, placebo-controlled, combined 2-fold cross-over and group-comparison, dose-escalation study to investigate safety, tolerability, pharmacodynamics, and pharmacokinetics of single oral doses of BAY 85-3934 in subjects with chronic kidney disease (CKD)]. www.clinicaltrials.gov/show/NCT01679587 (first received 6 September 2012).
NCT01971164 {published data only}
    1. Yamamoto H. Safety, tolerability, PK & PD study of JTZ-951 in anemic subjects with end-stage renal disease [Randomized, single-blind, placebo-controlled, multiple ascending dose study to evaluate safety, tolerability, pharmacokinetics & pharmacodynamics of JTZ-951 administered once daily for 15 days in anemic subjects with end-stage renal disease]. www.clinicaltrials.gov/show/NCT01971164 (first received 29 October 2013).
NCT03992066 {published data only}
    1. NCT03992066. Study to evaluate the pharmacokinetics, pharmacodynamics, and safety of vadadustat in hemodialysis subjects with anemia associated with chronic kidney disease [A phase 1b, randomized, open-label study to evaluate the pharmacokinetics, pharmacodynamics, and safety of vadadustat in hemodialysis subjects with anemia associated with chronic kidney disease]. www.clinicaltrials.gov/show/NCT03992066 (first received 19 June 2019).
NCT04059913 {published data only}
    1. NCT04059913. Evaluate the efficacy and safety of multiple roxadustat dosing regimens for the treatment of anemia in dialysis subjects with chronic kidney disease [A prospective, randomized, open-label, multi-center study to evaluate the efficacy and safety of multiple roxadustat dosing regimens for the treatment of anemia in dialysis subjects with chronic kidney disease]. www.clinicaltrials.gov/show/NCT04059913 (first received 16 August 2019).
Pai 2015 {published data only}
    1. Pai S, Koretomo R, Tamaki S, Berg J, Marbury T, Galloway C, et al. JTZ-951, a novel HIF-PHD inhibitor, demonstrates increases in hemoglobin, iron mobilization, reproducible pharmacokinetics, and safety following once daily administration for 15 days in patients with anemia receiving hemodialysis [abstract no: FP658]. Nephrology Dialysis Transplantation 2015;30:iii293-4. [EMBASE: 72207075]
Parmar 2019 {published data only}
    1. Parmar D, Kansagra K. A phase II trial to assess safety, tolerability and efficacy of phd-2 inhibitor (desidustat-zyan1) in the treatment of anemia in pre-dialysis chronic kidney disease patients [abstract no: MON-318]. Kidney International Reports 2019;4(7 Suppl):S430. [EMBASE: 2002179966]
    1. Parmar DV, Kansagra KA, Patel JC, Joshi SN, Sharma NS, Shelat AD, et al. Outcomes of desidustat treatment in people with anemia and chronic kidney disease: a phase 2 study. American Journal of Nephrology 2019;49(6):470-8. [MEDLINE: ] - PubMed
Provenzano 2011 {published data only}
    1. Provenzano R, Goodkin D, Klaus S, Linde P, Kazazi F, Lee T, et al. Evaluation of FG-4592, a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor, to treat anemia in hemodialysis patients [abstract no: 253]. American Journal of Kidney Diseases 2011;57(4):A80. [EMBASE: 70379812]
Provenzano 2011a {published data only}
    1. Provenzano R, Tumlin J, Zabaneh R, Chou J, Hemmerich S, Neff TB, et al. Oral hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) for treatment of anemia in chronic kidney disease: a placebo-controlled study of pharmacokinetic and pharmacodynamic profiles in hemodialysis patients. Journal of Clinical Pharmacology 2020;60(11):1432-40. [MEDLINE: ] - PMC - PubMed
    1. Provenzano R, Tumlin J, Zabaneh R, Linde P, Chou J, Zhong M, et al. Pharmacokinetics of oral FG-4592 to treat anemia in hemodialysis (HD) patients (PTS) [abstract no: 254]. American Journal of Kidney Diseases 2011;57(4):A80. [EMBASE: 70379813]
Provenzano 2016b {published data only}
    1. Besarab A, Belo D, Diamond S, Martin E, Sun C, Lee T, et al. Evaluation of hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for hemoglobin correction and maintenance in nondialysis chronic kidney disease patients for 16 and 24 weeks [abstract no: FP215]. Nephrology Dialysis Transplantation 2012;27(Suppl 2):ii144-5. [EMBASE: 70765709]
    1. Besarab A, Provenzano R, Fishbane S, Sun CH, Belo DS, Neff TB, et al. FG-4592 oral hypoxia-inducible factor prolyl hydroxylase inhibitor corrects anemia in nondialysis CKD patients without IV iron [abstract no: TH-PO364]. Journal of the American Society of Nephrology 2011;22(Abstract Suppl):196A.
    1. Provenzano R, Besarab A, Sun CH, Diamond SA, Durham JH, Cangiano JL, et al. Oral hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) for the treatment of anemia in patients with CKD. Clinical Journal of the American Society of Nephrology: CJASN 2016;11(6):982-91. [MEDLINE: ] - PMC - PubMed
Wiecek 2005 {published data only}
    1. Wiecek A, Piecha G, Ignacy W, Schmidt R, Neumayer HH, Scigalla P, et al. Pharmacological stabilization of HIF increased hemoglobin concentration in anemic patients with chronic kidney disease [abstract no: MO24]. Nephrology Dialysis Transplantation 2005;20(Suppl 5):v195.

References to studies awaiting assessment

FO2RWARD‐2 2019 {published data only}
    1. NCT03799627. Study of vadadustat in hemodialysis patients with anemia switching from epoetin alfa (FO2RWARD-2) [Phase 2, randomized, open-label, active-controlled, efficacy, safety, pharmacokinetics, and pharmacodynamics study of oral vadadustat for the treatment of anemia in hemodialysis subjects converting from epoetin alfa (FO2RWARD-2)]. www.clinicaltrials.gov/show/NCT03799627 (first received 10 January 2019).

References to ongoing studies

ASCEND‐FBF 2018 {published data only}
    1. NCT03446612. Anemia study in chronic kidney disease (CKD) : erythropoiesis via a novel prolyl hydroxylase inhibitor (PHI) daprodustat -forearm blood flow (ASCEND-FBF) [A randomized, repeat dose, open label, parallel group, multi-center study to evaluate the effect of daprodustat compared to darbepoetin alfa on forearm blood flow in participants with anemia of chronic kidney disease that are not dialysis dependent]. www.clinicaltrials.gov/show/NCT03446612 (first received 27 February 2018).
CTRI/2019/06/019635 {published data only}
    1. Kansagra K. Desidustat in the treatment of anemia in chronic kidney disease (CKD) [A phase 3, multicenter, multicountry, open-label, randomized, active-controlled clinical trial to evaluate the efficacy and safety of desidustat versus darbepoetin for the treatment of anemia in patients with chronic kidney disease (CKD) who are not on dialysis.]. ctri.nic.in/Clinicaltrials/showallp.php?mid1=33329&EncHid=&userN... (first received 12 June 2019).
DREAM‐D 2019 {published data only}
    1. Kansagra K. Desidustat in the treatment of anemia in CKD. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=36915&EncHid=&u... (first received 11 December 2019).
NCT04027517 {published data only}
    1. Lee JW. A study to evaluate efficacy and safety of JTZ-951 compared to darbepoetin alfa in Korean renal anemia patients receiving hemodialysis [A multi-center, randomized, open-label, active-controlled, parallel-group, phase iii study to compare the efficacy and safety of JTZ-951 with darbepoetin alfa in anemic patients with chronic kidney disease receiving maintenance hemodialysis]. www.clinicaltrials.gov/show/NCT04027517 (first received 22 July 2019).
NCT04134026 {published data only}
    1. Liu H. Evaluate the efficacy and safety of roxadustat for the treatment of anemia and risks of cardiovascular and cerebrovascular events in ESRD newly initiated dialysis patients [Phase 4 multicenter, randomized, open-lable, active-controlled study of the efficacy and safty of roxadustat for the treatment of anemia and risks of cardiovascular and cerebrovascular events in incident-dialysis patients]. www.clinicaltrials.gov/show/NCT04134026 (first received 21 October 2019).
NCT04313153 {published data only}
    1. NCT04313153. Trial evaluating the efficacy and safety of oral vadadustat once daily (QD) and three times weekly (TIW) for the maintenance treatment of anemia in hemodialysis subjects converting from erythropoiesis-stimulating agents (ESAs) [Phase 3b, randomized, open-label, active-controlled trial evaluating the efficacy and safety of oral vadadustat once daily (QD) and three times weekly (TIW) for the maintenance treatment of anemia in hemodialysis subjects converting from erythropoiesis-stimulating agents (ESAs)]. www.clinicaltrials.gov/show/NCT04313153 (first received 18 March 2020).
PER‐038‐14 {published data only}
    1. PER-038-14. A phase 3, multicenter, randomized, open-label active-controlled study of the efficacy and safety of FG-4592 in the treatment of anemia in incident-dialysis patients. www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=038-14 (first received 11 December 2014).
SLCTR‐2019‐032 {published data only}
    1. Nazar AL. A randomized, active-controlled clinical trial to evaluate the efficacy and safety of desidustat versus darbepoetin for the treatment of anemia in patients with chronic kidney disease (CKD) who are not on dialysis [A phase 3, multicenter, multi-country, open-label, randomized, active-controlled clinical trial to evaluate the efficacy and safety of desidustat versus darbepoetin for the treatment of anemia in patients with chronic kidney disease (CKD) who are not on dialysis]. slctr.lk/trials/slctr-2019-032 (first received 13 August 2019).

Additional references

Babitt 2012
    1. Babitt JL, Lin HY. Mechanisms of anemia in CKD. Journal of the American Society of Nephrology 2012;23(10):1631-4. [MEDLINE: ] - PMC - PubMed
Bernhardt 2010
    1. Bernhardt WM, Wiesener MS, Scigalla P, Chou J, Schmeider RE, Günzler V, et al. Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. Journal of the American Society of Nephrology 2010;21(12):2151-6. [MEDLINE: ] - PMC - PubMed
El‐Achkar 2005
    1. El-Achkar TM, Ohmit SE, McCullogh PA, Crook ED, Brown WW, Grimm R, et al. Higher prevalence of anemia with diabetes mellitus in moderate kidney insufficiency: The Kidney Early Evaluation Program. Kidney International 2005;67(4):1483-8. [MEDLINE: ] - PubMed
FDA Briefing Document 2021
    1. US Food & Drug Administration. Cardiovascular and Renal Drugs Advisory Committee Meeting July 15, 2021 Roxadustat. www.fda.gov/media/150728/download (accessed 10 May 2022).
Gansevoort 2013
    1. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 2013;382(9889):339-52. [MEDLINE: ] - PubMed
GBD Kidney Disease 2017
    1. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020;395(10225):709-33. [MEDLINE: ] - PMC - PubMed
Global Burden of Disease 2017
    1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [Erratum in: Lancet. 2019 Jun 22;393(10190):e44]. Lancet 2018;392(10159):1789-858. [MEDLINE: ] - PMC - PubMed
GRADE 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924-6. [MEDLINE: ] - PMC - PubMed
GRADE 2011
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383-94. [MEDLINE: ] - PubMed
Haase 2021
    1. Haase VH. Hypoxia-inducible factor-prolyl hydroxylase inhibitors in the treatment of anemia of chronic kidney disease. Kidney Int Suppl (2011) 2021;11(1):8-25. doi: 10.1016/j.kisu.2020.12.002. - PMC - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60. [MEDLINE: ] - PMC - PubMed
Higgins 2020
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane, 2020. Available from www.training.cochrane.org/handbook.
KDIGO Clinical Practice Guideline Anemia 2012
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney International Supplements 2012;2(4):279-335. [https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-Anemia-Guideline...]
KDIGO Clinical Practice Guideline CKD 2012
    1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International Supplements 2013;3(1):1-150. [https://kdigo.org/guidelines/ckd-evaluation-and-management/] - PMC - PubMed
LaGory 2016
    1. LaGory EL, Giaccia AJ. The ever expanding role of HIF in tumour and stromal biology. Nature Cell Biology 2016;18(4):356-65. [MEDLINE: ] - PMC - PubMed
Li 2020
    1. Li ZL, Tu Y, Liu BC. Treatment of renal anemia with roxadustat: advantages and achievement. Kidney Diseases 2020;6(2):65–73. [MEDLINE: ] - PMC - PubMed
Liu 2012
    1. Liu Q, Davidoff O, Niss K, Haase VH. Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis. Journal of Clinical Investigation 2012;122(12):4635–44. [MEDLINE: ] - PMC - PubMed
Ma 1999
    1. Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. Journal of the American Society of Nephrology 1999;10(3):610-9. [MEDLINE: ] - PubMed
Mathias 2020
    1. Mathias SD, Blum SI, Sikirica V, Johansen KL, Colwell HH, Okoro T. Symptoms and impacts in anemia of chronic kidney disease. Journal of Patient-Reported Outcomes 2020;4(1):64. [MEDLINE: ] - PMC - PubMed
Nemeth 2009
    1. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematologica 2009;122(2-3):78–86. [MEDLINE: ] - PMC - PubMed
Phrommuntikul 2007
    1. Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007;369(9559):381-8. [MEDLINE: ] - PubMed
Provenzano 2016c
    1. Provenzano R, Besarab A, Sun CH, Diamond SA, Durham JH, Cangiano JL, et al. Oral hypoxia-inducible factor prolyl hydroxylase inhibitor Roxadustat (FG-4592) for the treatment of anemia in patients with CKD. Clinical Journal of The American Society of Nephrology: CJASN 2016;11(6):982-91. [MEDLINE: ] - PMC - PubMed
Renassia 2019
    1. Renassia C, Peyssonnaux P. New insights into the links between hypoxia and iron homeostasis. Current Opinion in Hematology 2019;26(3):125-30. [MEDLINE: ] - PMC - PubMed
Schunemann 2020a
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’ tables and grading the certainty of the evidence. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane, 2020. www.training.cochrane.org/handbook.
Schunemann 2020b
    1. Schünemann HJ, Vist GE, Higgins JP, Santesso N, Deeks JJ, Glasziou P, et al. Chapter 15: Interpreting results and drawing conclusions. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane, 2020. Available from www.training.cochrane.org/handbook.
Schwartz 2019
    1. Schwartz AJ, Das NK, Ramakrishnan SK, Jain C Jurkovic MT, Wu J, et al. Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload. Journal of Clinical Investigation 2019;129(1):336-48. [MEDLINE: ] - PMC - PubMed
Semenza 2011
    1. Semenza GL. Oxygen sensing, homeostasis, and disease [Erratum in: N Engl J Med. 2011 Sep 8;365(10):968]. New England Journal of Medicine 2011;365(6):537-47. [MEDLINE: ] - PubMed
SONG 2017
    1. SONG Initiative. The SONG Handbook Version 1.0. www.songinitiative.org/reports-and-publications/ 2017.
van Haalen 2020
    1. Haalen H, Jackson J, Spinowitz B, Milligan G, Moon R. Impact of chronic kidney disease and anemia on health-related quality of life and work productivity: analysis of multinational real-world data. BMC Nephrology 2020;21(1):88. [MEDLINE: ] - PMC - PubMed
Wang 2020
    1. Wang B, Yin Q, Han YC, Wu M, Li ZL, Tu Y, et al. Effect of hypoxia-inducible factor-prolyl hydroxylase inhibitors on anemia in patients with CKD: a meta-analysis of randomized controlled trials including 2804 patients. Renal Failure 2020;42(1):912-25. [MEDLINE: ] - PMC - PubMed
Wyld 2019
    1. Wyld ML, Morton RL, Calyton P, Wong MG, Jardine M, Polkinghorne K, et al. The impact of progressive chronic kidney disease on health-related quality of life: A 12-year community cohort study. Quality of Life Research 2019;28(8):2081-90. [MEDLINE: ] - PubMed
Zhong 2018
    1. Zhong H, Zhou T, Li H, Zhong Z. The role of hypoxia-inducible factor stabilizers in the treatment of anemia in patients with chronic kidney disease. Drug Design, Development & Therapy 2018;12:3003-11. [MEDLINE: ] - PMC - PubMed

References to other published versions of this review

Natale 2020
    1. Natale P, Palmer SC, Tong A, Ruospo M, Hodson EM, Cooper TE, et al. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database of Systematic Reviews 2020, Issue 10. Art. No: CD013751. [DOI: 10.1002/14651858.CD013751] - DOI - PMC - PubMed

Associated data