Multiphoton imaging for assessing renal disposition in acute kidney injury

Xin Liu, Xiaowen Liang, Haolu Wang, Darren M. Roberts, Michael S. Roberts

    Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

    Abstract

    Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

    Original languageEnglish
    Title of host publicationSPIE BioPhotonics Australasia
    EditorsEwa M. Goldys, Mark R. Hutchinson
    PublisherSPIE
    ISBN (Electronic)9781510604346
    DOIs
    Publication statusPublished - 2016
    EventSPIE BioPhotonics Australasia - Adelaide, Australia
    Duration: 17 Oct 201619 Oct 2016

    Publication series

    NameProceedings of SPIE - The International Society for Optical Engineering
    Volume10013
    ISSN (Print)0277-786X
    ISSN (Electronic)1996-756X

    Conference

    ConferenceSPIE BioPhotonics Australasia
    Country/TerritoryAustralia
    CityAdelaide
    Period17/10/1619/10/16

    Fingerprint

    Dive into the research topics of 'Multiphoton imaging for assessing renal disposition in acute kidney injury'. Together they form a unique fingerprint.

    Cite this