The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Inhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD
Open accessAbstract
The reasons for inadequate production of erythropoietin (EPO) in patients with ESRD are poorly understood. A better understanding of EPO regulation, namely oxygen-dependent hydroxylation of the hypoxia-inducible transcription factor (HIF), may enable targeted pharmacological intervention. Here, we tested the ability of fibrotic kidneys and extrarenal tissues to produce EPO. In this phase 1 study, we used an orally active prolyl-hydroxylase inhibitor, FG-2216, to stabilize HIF independent of oxygen availability in 12 hemodialysis (HD) patients, six of whom were anephric, and in six healthy volunteers. FG-2216 increased plasma EPO levels 30.8-fold in HD patients with kidneys, 14.5-fold in anephric HD patients, and 12.7-fold in healthy volunteers. These data demonstrate that pharmacologic manipulation of the HIF system can stimulate endogenous EPO production. Furthermore, the data indicate that deranged oxygen sensing--not a loss of EPO production capacity--causes renal anemia.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“and has the potential to benefit patients with anemia that results from inadequate EPO production.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [235]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Pharmacological inactivation of PHD enzymes with 2OG analogs increases serum EPO levels in animal models and in humans”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [235]
In the citing paper
“recent phase I studies have shown that systemic treatment with HIF activators is safe and potentially useful in boosting EPO levels in patients with end-stage renal disease [121].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [121]
In the citing paper
“recent phase I studies have shown that systemic treatment with HIF activators is safe and potentially useful in boosting EPO levels in patients with end-stage renal disease [121].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [121]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068
Hypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676
Erythropoietin: structure, control of production, and function
JELKMANN, W. E. B. (1992) · Physiological Reviews · doi:10.1152/physrev.1992.72.2.449 · Cited by 1,167
Chronic Hypoxia and Tubulointerstitial Injury
Nangaku, M. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005070757 · Cited by 1,146
Widespread, hypoxia‐inducible expression of HIF‐2α in distinct cell populations of different organs
Wiesener, M. S., Jürgensen, J. S., Rosenberger, C., Scholze, C. K., Hörstrup, J. H., Warnecke, C., Mandriota, S. J., Bechmann, I., Frei, U. A., Pugh, C. W., et al. (2002) · The FASEB Journal · doi:10.1096/fj.02-0445fje · Cited by 770
Self-citationIvan, M., Haberberger, T., Gervasi, D. C., Michelson, K. S., Günzler, V., Kondo, K., Yang, H., Sorokina, I., Conaway, R. C., Conaway, J. W., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192342099 · Cited by 561
Self-citationDisruption of oxygen homeostasis underlies congenital Chuvash polycythemia
Ang, S. O., Chen, H., Hirota, K., Gordeuk, V. R., Jelinek, J., Guan, Y., Liu, E., Sergueeva, A. I., Miasnikova, G. Y., Mole, D., et al. (2002) · Nature Genetics · doi:10.1038/ng1019 · Cited by 510
Warnecke, C., Zaborowska, Z., Kurreck, J., Erdmann, V. A., Frei, U. A., Wiesener, M. S., & Eckardt, K. (2004) · The FASEB Journal · doi:10.1096/fj.04-1640fje · Cited by 406
Self-citationIdentification of the renal erythropoietin-producing cells using transgenic mice
Maxwell, P. H., Osmond, M. K., Pugh, C. W., Heryet, A. R., Nicholls, L. G., Tan, C. C., Doe, B., Ferguson, D. J. P., Johnson, M. H., & Ratcliffe, P. J. (1993) · Kidney International · doi:10.1038/ki.1993.362 · Cited by 388
Cited by
Sorted by citations
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
Ischemia and reperfusion—from mechanism to translation
Eltzschig, H. K., & Eckle, T. D. L. G. (2011) · Nature Medicine · doi:10.1038/nm.2507 · Cited by 3,468
Regulation of erythropoiesis by hypoxia-inducible factors
Haase, V. H. (2013) · Blood Reviews · doi:10.1016/j.blre.2012.12.003 · Cited by 787
High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq
Schödel, J., Oikonomopoulos, S., Ragoussis, J., Pugh, C. W., Ratcliffe, P. J., & Mole, D. R. (2011) · Blood · doi:10.1182/blood-2010-10-314427 · Cited by 724
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis
Chen, N., Hao, C., Liu, B., Lin, H., Wang, C., Xing, C., Liang, X., Jiang, G., Liu, Z., Li, X., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1901713 · Cited by 630
Metadata
- Authors
- Bernhardt, W. M., Wiesener, M. S., Scigalla, P., Chou, J., Schmieder, R. E., Günzler, V., & Eckardt, K.-U.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Venue
- Journal of the American Society of Nephrology
- Published
- 2010-12
- Volume
- 21
- Issue
- 12
- Pages
- 2151-2156
- ISSN
- 1046-6673 (ISSN-L)
- PMC
- PMC3014028
- OpenAlex
- W2136732413
- Cited by
- 340
- References
- 33
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 8 · 2023: 20 · 2022: 23 · 2021: 31 · 2020: 16 · 2019: 13 · 2018: 18 · 2017: 25 · 2016: 28 · 2015: 30 · 2014: 22 · 2013: 34 · 2012: 28
- FWCI
- 17.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- FibroGen
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- erythropoietin, prolyl hydroxylase inhibitors, hypoxia-inducible factor, end-stage renal disease, anemia of chronic kidney disease, hemodialysis, oxygen sensing, anephric patients
- MeSH terms
- Administration, Oral, Adult, Aged, Aged, 80 and over, Anemia, Erythropoietin, Female, Follow-Up Studies, Renal Dialysis, Humans, Kidney Failure, Chronic, Male, Middle Aged, Nephrectomy, Procollagen-Proline Dioxygenase, Reference Values, Treatment Outcome, Risk Assessment, Hypoxia-Inducible Factor 1, alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
