ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: SA-PO180

Clonal Hematopoiesis of Indeterminate Potential Associates with Severe AKI

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Chen, Jianchun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Vlasschaert, Caitlyn, Queen University, Kingston, Ontario, Canada
  • Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • Zhang, Ming-Zhi, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Harris, Raymond C., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of hematopoietic stem cells due to somatic mutations like TET2 gene mutation, without evidence of hematologic malignancy or cytopenia. CHIP is associated with a pro-inflammatory state. The role of inflammation in acute kidney injury (AKI) among individuals with CHIP remains unclear.


Bone marrow cells (BMC) were collected from recipient mice (CD45.1 isotype), Tet2-deficient and control mice (CD45.2 isotype). Lethally irradiated male recipient mice underwent retroorbital injection of 5 × 106 BMC, consisting of 80% recipient cells and 20% Tet2-deficient (Tet2-/-) or control (Tet2+/+) cells. Flow cytometry confirmed successful engraftment and clonal expansion of Tet2-deficient cells, and then the chimeric mice underwent unilateral kidney vascular clamping with contralateral nephrectomy (Unx-IRI). Renal function was assessed by BUN and creatinine levels, and kidney macrophages were isolated for analysis.


The chimeric mice with Tet2-/- BMC developed CHIP, indicated by flow cytometry of peripheral blood cells. Tet2-/- mice exhibited increased CD45.2 cells in the intrinsic myeloid kidney cell population. Following Unx-IRI, Tet2-/- mice had more severe kidney injury compared to control mice. Higher levels of tubule injury markers (KIM-1, NGAL) and more severe tubule injury were observed in Tet2-/- mice at 8 days after Unx-IRI. The kidneys of Tet2-/- mice displayed elevated expression of proinflammatory cytokines (Tnf, Il6, Il1b), chemokines (Ccl2, Ccl3), profibrotic genes (Tgfb, Ctgf, Acta2), and extracellular matrix-associated genes (Col1a1, Col3a1, Fn, Vim) compared to Tet2+/+ mice. Macrophages isolated from the kidneys of Tet2-/- mice exhibited increased expression of proinflammatory cytokines both before and after injury. Additionally, increased co-expression of NLRP3 inflammasome and IL-1β with CD68-positive macrophages was observed in kidneys only in the CD45.2 macrophages and not in the CD45.1 macrophages.


This study demonstrates that CHIP is associated with an increased risk of severe AKI in this mouse model, potentially caused by enhanced infiltration of inflammatory cells into the kidneys and subsequent excessive production of proinflammatory cytokines and chemokines.


  • NIDDK Support