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Cited by 295

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

Preconditional Activation of Hypoxia-Inducible Factors Ameliorates Ischemic Acute Renal Failure

Bernhardt, Wanja M., Ca[Combining Circumflex Accent]mpean, Valentina, Kany, Sarah, Ju[Combining Diaeresis]rgensen, Jan-Steffen, Weidemann, Alexander, Warnecke, Christina, Arend, Michael, Klaus, Stephen, Gu[Combining Diaeresis]nzler, Volkmar, Amann, Kerstin, Willam, Carsten, Wiesener, Michael S., Eckardt, Kai-Uwe·2006·Journal of the American Society of Nephrology

Abstract

Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism of cellular adaptation to low oxygen. Normoxic degradation of HIF is mediated by oxygen-dependent hydroxylation of specific prolyl residues of the regulative alpha-subunits by HIF prolyl hydroxylases (PHD). It was hypothesized that inhibition of HIF degradation by either hypoxia or pharmacologic inhibition of PHD would confer protection against subsequent ischemic injury. For testing this hypothesis ischemic acute renal failure was induced in rats by 40 min of clamping of the left renal artery after right-sided nephrectomy. Before surgery, pretreatment with either carbon monoxide, leading to tissue hypoxia, or the novel PHD inhibitor FG-4487 was applied. No toxic effects of FG-4487 were observed. Both pretreatments strongly induced the accumulation of HIF-1alpha and HIF-2alpha in tubular and peritubular cells, respectively, as well as HIF target gene expression. The course of subsequent ischemic injury was significantly ameliorated by both strategies of preconditioning, as evident from a significant improvement of serum creatinine and serum urea after 24 and 72 h. Furthermore, tissue injury and apoptosis were less severe, which were quantified by application of a standardized histologic scoring system in a blinded manner. In conclusion, the data provide proof of principle that preconditional activation of the HIF system protects against ischemic injury. Inhibiting the activity of HIF hydroxylases therefore seems to have considerable clinical perspectives.

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Metadata

Authors
Bernhardt, W. M., Ca[Combining Circumflex Accent]mpean, V., Kany, S., Ju[Combining Diaeresis]rgensen, J.-S., Weidemann, A., Warnecke, C., Arend, M., Klaus, S., Gu[Combining Diaeresis]nzler, V., Amann, K., Willam, C., Wiesener, M. S., & Eckardt, K.-U.
Venue
Journal of the American Society of Nephrology
Published
2006-07
Volume
17
Issue
7
Pages
1970-1978
ISSN
1046-6673 (ISSN-L)
OpenAlex
W2136548506
Cited by
295
References
32
FWCI
15.13
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Preconditional Activation of Hypoxia-Inducible Factors Ameliorates Ischemic Acute Renal Failure. https://app.cochat.ai/papers/10.1681/asn.2005121302
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Bernhardt, W. M., Ca[Combining Circumflex Accent]mpean, V., Kany, S., Ju[Combining Diaeresis]rgensen, J.-S., Weidemann, A., Warnecke, C., Arend, M., Klaus, S., Gu[Combining Diaeresis]nzler, V., Amann, K., Willam, C., Wiesener, M. S., & Eckardt, K.-U. (2006). Preconditional Activation of Hypoxia-Inducible Factors Ameliorates Ischemic Acute Renal Failure. Journal of the American Society of Nephrology. https://doi.org/10.1681/asn.2005121302

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.