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ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

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Kidney Week

Abstract: FR-PO347

Adaptive and Maladaptive Kidney Repair Models Reveal Distinct Pathways of Myeloid and Lymphoid Cell Recruitment and Activation

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms


  • Xu, Leyuan, Yale University School of Medicine, New Haven, Connecticut, United States
  • Cantley, Lloyd G., Yale University School of Medicine, New Haven, Connecticut, United States

Incomplete repair after acute kidney injury (AKI) can lead to progressive fibrosis and development of chronic kidney disease (CKD). We have previously shown that unilateral ischemia-reperfusion kidney injury with contralateral nephrectomy (IRI/CL-NX) results in significantly less fibrosis in the injured kidney than does unilateral IRI with the contralateral kidney intact (U-IRI). Here, we investigated the mechanism of this difference by comparing an identical time of ischemic injury between mice subjected to U-IRI and those subjected to IRI/CL-NX.


Male wild-type mice were subjected to warm U-IRI or IRI/CL-NX (27 min). The injured kidney was removed on day 1, 7, 14 or 30 after IRI (n=10/group). Renal function was assessed by serum creatinine and BUN. Renal fibrosis and macrophage accumulation were assessed by Sirius red staining and IHC staining for F4/80. Kidney injury, inflammation, accumulation of myeloid and lymphoid cells, chemoattractant and survival factor expression levels were assessed by qPCR at each time point.


This analysis revealed that initial recruitment and activation of macrophages, dendritic cells and T cells as well as myofibroblast activation and profibrotic gene expression were equivalent through day 7 in these two models. However, in the IRI/CL-NX model macrophage numbers declined after day 7 with tubule regeneration and only modest interstitial fibrosis on day 30. In contrast, macrophages persisted and expressed significantly higher levels of profibrotic growth factors Pdgfb and Tgfb1 while dendritic cells and T cells significantly increased in numbers and expressed greater amounts of Tnfa and Il1b. These sustained immune responses correlated with progressive expression of collagen and fibronectin, sustained expression of Havcr1 and Lcn2, less tubule regeneration and greater kidney atrophy. The persistence of macrophages, dendritic cells and T cells in injured U-IRI kidneys highly correlated with sustained expression of the chemokines Ccl1, Ccl2 and Cx3cl1.


Abnormal accumulation of macrophages, dendritic cells and T cells may lead to progressive interstitial fibrosis, sustained inflammation and kidney injury in the setting of maladaptive kidney repair following IRI. Blocking homing chemokines may serve as a therapeutic target to attenuate CKD progression.


  • NIDDK Support