Evidence map›Paper›PMID 25392999›Full record

ArticlePloS one2014

Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat) stimulates erythropoietin production without hypertensive effects.

Ingo Flamme, Felix Oehme, Peter Ellinghaus, Mario Jeske, Jörg Keldenich, Uwe Thuss

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 4 pooled it
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 4 syntheses or guidelines pooled it, 170 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Molidustat for the treatment of anemia in Japanese patients undergoing peritoneal dialysis: a single-arm, open-label, phase 3 study.Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy · 2022
    Trial
  6. Molidustat for anemia correction in Japanese patients undergoing hemodialysis: a single-arm, phase 3 study.Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy · 2021
    Trial
  7. Trial
  8. Trial
  9. Trial
  10. KDIGO 2026 Clinical Practice Guideline for Anemia in Chronic Kidney Disease (CKD): a commentary from the European Renal Best Practice (ERBP).Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Article
  11. Review
  12. Navigating Anemia Therapy in CKD With Hypoxia-Inducible Factor Activators: A Review.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2026
    Review
  13. Article
  14. Article
  15. Article
  16. The Role of Hypoxia in Longevity.Aging and disease · 2025
    Review
  17. Review
  18. Review
  19. Article
  20. Review

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Ingo FlammeCardiology/Hematology, Acute Care Research, Global Drug Discovery, Bayer Pharma AG, Wuppertal, Germany.
Felix OehmeBiotech Development, Global Biologics, Bayer Pharma AG, Wuppertal, Germany.
Peter EllinghausClinical Science, Global Biomarkers, Bayer Pharma AG, Wuppertal, Germany.
Mario JeskeGlobal Chemical Product Development, Bayer Pharma AG, Wuppertal, Germany.
Jörg KeldenichDrug Metabolism and Pharmacokinetics, Global Early Development, Bayer Pharma AG, Wuppertal, Germany.
Uwe ThussDrug Metabolism and Pharmacokinetics, Global Early Development, Bayer Pharma AG, Wuppertal, Germany.
Bayer (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oxygen sensing by hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) is the dominant regulatory mechanism of erythropoietin (EPO) expression. In chronic kidney disease (CKD), impaired EPO expression causes anemia, which can be treated by supplementation with recombinant human EPO (rhEPO). However, treatment can result in rhEPO levels greatly exceeding the normal physiological range for endogenous EPO, and there is evidence that this contributes to hypertension in patients with CKD. Mimicking hypoxia by inhibiting HIF-PHs, thereby stabilizing HIF, is a novel treatment concept for restoring endogenous EPO production. HIF stabilization by oral administration of the HIF-PH inhibitor BAY 85-3934 (molidustat) resulted in dose-dependent production of EPO in healthy Wistar rats and cynomolgus monkeys. In repeat oral dosing of BAY 85-3934, hemoglobin levels were increased compared with animals that received vehicle, while endogenous EPO remained within the normal physiological range. BAY 85-3934 therapy was also effective in the treatment of renal anemia in rats with impaired kidney function and, unlike treatment with rhEPO, resulted in normalization of hypertensive blood pressure in a rat model of CKD. Notably, unlike treatment with the antihypertensive enalapril, the blood pressure normalization was achieved without a compensatory activation of the renin-angiotensin system. Thus, BAY 85-3934 may provide an approach to the treatment of anemia in patients with CKD, without the increased risk of adverse cardiovascular effects seen for patients treated with rhEPO. Clinical studies are ongoing to investigate the effects of BAY 85-3934 therapy in patients with renal anemia.

Indexed as

AnemiaAnimalsErythropoietinFemaleHumansHypoxia-Inducible Factor-Proline DioxygenasesMacaca fascicularisMalePyrazolesRatsRats, WistarRenal Insufficiency, ChronicTriazolesUp-RegulationErythropoietinHypoxia-Inducible Factor-Proline DioxygenasesmolidustatPyrazolesTriazoles

Identifiers

PMID25392999
PMCPMC4230943
OpenAlexW2087830638

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.