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  1. Article ; Online: Molecular nephrology: types of acute tubular injury.

    Desanti De Oliveira, Beatriz / Xu, Katherine / Shen, Tian H / Callahan, Miriam / Kiryluk, Krzysztof / D'Agati, Vivette D / Tatonetti, Nicholas P / Barasch, Jonathan / Devarajan, Prasad

    Nature reviews. Nephrology

    2019  Volume 15, Issue 10, Page(s) 599–612

    Abstract: The acute loss of kidney function has been diagnosed for many decades using the serum concentration of creatinine - a muscle metabolite that is an insensitive and non-specific marker of kidney function, but is now used for the very definition of acute ... ...

    Abstract The acute loss of kidney function has been diagnosed for many decades using the serum concentration of creatinine - a muscle metabolite that is an insensitive and non-specific marker of kidney function, but is now used for the very definition of acute kidney injury (AKI). Fortunately, myriad new tools have now been developed to better understand the relationship between acute tubular injury and elevation in serum creatinine (SCr). These tools include unbiased gene and protein expression analyses in kidney, urine and blood, the localization of specific gene transcripts in pathological biopsy samples by rapid in-situ RNA technology and single-cell RNA-sequencing analyses. However, this molecular approach to AKI has produced a series of unexpected problems, because the expression of specific kidney-derived molecules that are indicative of injury often do not correlate with SCr levels. This discrepancy between kidney injury markers and SCr level can be reconciled by the recognition that many separate subtypes of AKI exist, each with distinct patterning of molecular markers of tubular injury and SCr data. In this Review, we describe the weaknesses of isolated SCr-based diagnoses, the clinical and molecular subtyping of acute tubular injury, and the role of non-invasive biomarkers in clinical phenotyping. We propose a conceptual model that synthesizes molecular and physiological data along a time course spanning from acute cellular injury to organ failure.
    MeSH term(s) Acute Kidney Injury/blood ; Acute Kidney Injury/diagnosis ; Acute Kidney Injury/metabolism ; Biomarkers/blood ; Creatinine/blood ; Humans
    Chemical Substances Biomarkers ; Creatinine (AYI8EX34EU)
    Language English
    Publishing date 2019-08-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2490366-8
    ISSN 1759-507X ; 1759-5061
    ISSN (online) 1759-507X
    ISSN 1759-5061
    DOI 10.1038/s41581-019-0184-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Snapshots of nascent RNA reveal cell- and stimulus-specific responses to acute kidney injury.

    Shen, Tian Huai / Stauber, Jacob / Xu, Katherine / Jacunski, Alexandra / Paragas, Neal / Callahan, Miriam / Banlengchit, Run / Levitman, Abraham D / Desanti De Oliveira, Beatriz / Beenken, Andrew / Grau, Madeleine S / Mathieu, Edwin / Zhang, Qingyin / Li, Yuanji / Gopal, Tejashree / Askanase, Nathaniel / Arumugam, Siddarth / Mohan, Sumit / Good, Pamela I /
    Stevens, Jacob S / Lin, Fangming / Sia, Samuel K / Lin, Chyuan-Sheng / D'Agati, Vivette / Kiryluk, Krzysztof / Tatonetti, Nicholas P / Barasch, Jonathan

    JCI insight

    2022  Volume 7, Issue 6

    Abstract: The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In ... ...

    Abstract The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours. To detect acute responses to clinically relevant stimuli, we created mice expressing Rosa26-floxed-stop uracil phosphoribosyltransferase (Uprt) and inoculated 4-thiouracil (4-TU) to tag nascent RNA at selected time points. Cre-driven 4-TU-tagged RNA was isolated from intact kidneys and demonstrated that volume depletion and ischemia induced different genetic programs in collecting ducts and intercalated cells. Even lineage-related cell types expressed different genes in response to the 2 stressors. TU tagging also demonstrated the transient nature of the responses. Because we placed Uprt in the ubiquitously active Rosa26 locus, nascent RNAs from many cell types can be tagged in vivo and their roles interrogated under various conditions. In short, 4-TU labeling identifies stimulus-specific, cell-specific, and time-dependent acute responses that are otherwise difficult to detect with other technologies and are entirely obscured when sCr is the sole metric of kidney damage.
    MeSH term(s) Acute Kidney Injury ; Animals ; Gene Expression Profiling ; Mice ; RNA/metabolism
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2022-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.146374
    Database MEDical Literature Analysis and Retrieval System OnLINE

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