Impact of aging on transition of acute kidney injury to chronic kidney disease

Myung Gyu Kim, Jihyun Yang, Yoon Sook Ko, Hee Young Lee, Se Won Oh, Won Yong Cho, Sang Kyung Jo

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    27 Citations (Scopus)


    Acute kidney injury (AKI) increases the risk of end stage renal disease among the elderly, but the precise underlying mechanism is unknown. We investigated the effects of aging on AKI-to-chronic kidney disease (CKD) transition, focusing on renal inflammation. Aged and young C57BL/6 mice were subjected to bilateral ischemia-reperfusion injury (IRI). Baseline proinflammatory cytokine levels of kidneys were elevated in aged mice. After IRI, aged mice also showed persistent M1 dominant inflammation, with increased proinflammatory cytokines during the recovery phase. Persistent M1 inflammation was associated with blunted activation of CSF-1/IRF4 signal for M1/M2 polarization, but in vitro macrophage polarization with cytokine stimulation was not different between young and aged mononuclear cells. The tubular expressions of cell cycle arrest markers increased in aged mice during recovery phase, and in vitro transwell experiments showed that mononuclear cells or M1 macrophages co-cultured with arrested proximal tubular cells at G1 phase significantly impaired M2 polarization, suggesting that prolonged G1 arrest might be involved in persistent M1 inflammation in aged mice. Finally, M1 dominant inflammation in aged mice resulted in fibrosis progression. Our data show that impaired M2 polarization partially driven by senescent tubule cells with cell-cycle arrest may lead to an accelerated progression to CKD in the elderly.

    Original languageEnglish
    Article number18445
    JournalScientific reports
    Issue number1
    Publication statusPublished - 2019 Dec 1

    Bibliographical note

    Funding Information:
    This study was supported by a Korea University grant (project no. K1813181). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Publisher Copyright:
    © 2019, The Author(s).

    ASJC Scopus subject areas

    • General


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