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Key Event: 819

Key Event Title

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

Decreased, Glomerular filtration

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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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
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term
kidney

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

Process	Object	Action
glomerular filtration		decreased

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
Kidney dysfunction	KeyEvent	Arthur Author (send email)	Under development: Not open for comment. Do not cite	Under Development
Activation of PKC leads to Kidney Failure	KeyEvent	Arthur Author (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

Term	Scientific Term	Evidence	Link
Sprague-Dawley	Sprague-Dawley		NCBI
human	Homo sapiens	High	NCBI
Vertebrates	Vertebrates	High	NCBI

Life Stages

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

Life stage	Evidence
All life stages	High
Old Age	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

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

The glomerulus is composed of a network of capillaries located within the Bowman's capsule, that functions as the kidney's filtration system. The glomerulus filtration is composed of endothelium, podocytes, and glomerular basement membrane which acts as an ultrafiltration system for the kidneys. As blood is filtered through the glomerulus, small molecules, waste, and fluid can pass through the capillaries into the tubule whereas large molecules including proteins and blood cells remain in the blood vessels the glomerulus is composed of (Arif & Nihalani, 2013). Glomerular filtration rate (GFR) is used as an indication of kidney function (Kaufman, 2023). Glomerular filtration can be affected by ailments such as HIV, aging, hypertension, diabetes, obesity, and cancers along with being influenced by medications/chemicals (Jamshidi, 2020 & Bjornstad, 2018). A reduction in glomerular filtration causes high levels of waste to accumulate in the blood causing chemical imbalances, and decreased excretion of toxins from the body (Pizzorno, 2015).

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 glomerular flow rate can be measured directly or indirectly through exogenous or endogenous filtration markers respectively. The indirect measurement of GFR is often referred to as the estimated GFR (eGFR), which remains the most used method of clinically measuring GFR. This is calculated by measuring levels of serum creatinine and cystatin C in urine samples (Bjornstad, 2018). This provides the opportunity to measure this ex vivo.

The direct measurements of GFR involving clearance measurements of filtration markers such as inulin, iohexol, and technetium 99m diethylenetriamine pentaacetic acid (^99mTc-DTPA). Measuring the clearance of inulin along with other urine clearance measurements has been considered the gold-standard for measuring GFR for several decades despite their associated difficulties such as availability, cost, and increased difficulty due to constant collection of specimens (Warwick & Holness, 2022) Therefore, the indirect measurement of eGFR is more time efficient and accurate to an extent (Bjornstad, 2018).

The levels of proteins in urine can also be used to evaluate glomerular filtration. An increase in protein in urine is a sign of decreased/impaired glomerular filtration. This can be evaluated either urine albumin-to-creatinine ratios or using a dipstick urinalysis test (Tonelli, 2011).

Domain of Applicability

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

Taxonomic Applicability: The key event applies to all vertebrates, since the glomerulus is kidney specific, and all vertebrates have kidneys.

Life Stage Applicability: The key event is not life stage specific since all life stages have glomerulus in their kidneys, however the key event is exuberated at higher ages. The decline in filtration starts at around 30 years of age, but most prominent after 70 years of age (Noronha, 2022).

Sex Applicability: The key event is not sex specific since kidneys are not a sex specific organ. Therefore, both sexes have glomerulus present and can experience the key event.

References

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

Arif, E., & Nihalani, D. (2013). Glomerular Filtration Barrier Assembly: An insight. Postdoc journal : a journal of postdoctoral research and postdoctoral affairs, 1(4), 33–45.

Bjornstad, P., Karger, A. B., & Maahs, D. M. (2018). Measured GFR in Routine Clinical Practice-The Promise of Dried Blood Spots. Advances in chronic kidney disease, 25(1), 76–83. https://doi.org/10.1053/j.ackd.2017.09.003

Jamshidi, P., Najafi, F., Mostafaei, S. et al. Investigating associated factors with glomerular filtration rate: structural equation modeling. BMC Nephrol 21, 30 (2020). https://doi.org/10.1186/s12882-020-1686-2

Kaufman, D. P., Basit, H., & Knohl, S. J. (2023). Physiology, Glomerular Filtration Rate. In StatPearls. StatPearls Publishing.

Noronha, I. L., Santa-Catharina, G. P., Andrade, L., Coelho, V. A., Jacob-Filho, W., & Elias, R. M. (2022). Glomerular filtration in the aging population. Frontiers in medicine, 9, 769329. https://doi.org/10.3389/fmed.2022.769329

Pizzorno J. (2015). The Kidney Dysfunction Epidemic, Part 1: Causes. Integrative medicine (Encinitas, Calif.), 14(6), 8–13.

Tonelli, M., Muntner, P., Lloyd, A., Manns, B. J., James, M. T., Klarenbach, S., Quinn, R. R., Wiebe, N., Hemmelgarn, B. R., & Alberta Kidney Disease Network (2011). Using proteinuria and estimated glomerular filtration rate to classify risk in patients with chronic kidney disease: a cohort study. Annals of internal medicine, 154(1), 12–21. https://doi.org/10.7326/0003-4819-154-1-201101040-00003

Warwick, J., & Holness, J. (2022). Measurement of Glomerular Filtration Rate. Seminars in nuclear medicine, 52(4), 453–466. https://doi.org/10.1053/j.semnuclmed.2021.12.005