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Event: 1564

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Chemical induced Fanconi syndrome

Short name
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Chemical induced Fanconi syndrome
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Individual

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Complex I inhibition leads to Fanconi syndrome AdverseOutcome Evgeniia Kazymova (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

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Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Fanconi syndrome (FS) is characterized by a lack of reabsorption at the proximal tubule that can have genetic or non-genetic origins. As the proximal tubule is the place of extensive reabsorption from the glomerular filtrate in the nephron, this lack of transport results in dramatic consequences for electrolyte homeostasis. In particular, high levels of glucose, amino acids, bicarbonate, and phosphate are excreted instead of returning to the circulation.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

The main features of FS are detected in the urine: 

hyperphosphaturea, glycosurea and proteinurea are typical clinical features of FS, together with polyuria.

The lack in reabsorption of bicarbonate results in renal tubular acidosis, characterised by polyurea, hypokalemia and hyperchloremia.

Effects on bone mineralisation (adults) and development (children) is another characteristic of FS. The lack of reabsorption of phosphate leads to bone disorders (hypophosphatemic rickets in children and bone demineralisation in adults).

Association studies have linked several pharmacological drugs with the induction of non-congenital forms of FS (Hall, Bass, and Unwin 2014).

At the tissue level, a marked effect of these chemicals is the induction of mitochondrial cytopathy (swollen and dysmorphic mitochondria without cristae) (Herlitz et al. 2010).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

List of the literature that was cited for this KE description. More help

Hall, A. M., P. Bass, and R. J. Unwin. 2014. “Drug-Induced Renal Fanconi Syndrome.” Qjm 107(4):261–69.

Herlitz, Leal C. et al. 2010. “Tenofovir Nephrotoxicity: Acute Tubular Necrosis with Distinctive Clinical, Pathological, and Mitochondrial Abnormalities.” Kidney International 78(11):1171–77. Retrieved (http://dx.doi.org/10.1038/ki.2010.318).