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Kidney Week

Abstract: FR-PO313

A Novel Single Domain, I-Body AD-114, Attenuated Kidney Fibrosis Through Targeting CXCR4

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials


  • Cao, Qinghua, Kolling Institute, St. Leonards, New South Wales, Australia
  • Yi, Hao, Kolling Institute, St. Leonards, New South Wales, Australia
  • Huang, Chunling, University of Sydney, Sydney, New South Wales, Australia
  • Foley, Michael, La Trobe University, Melbourne, New South Wales, Australia
  • Pollock, Carol A., The University of Sydney, St. Leonards, New South Wales, Australia
  • Chen, Xinming, University of Sydney, Sydney, New South Wales, Australia

Group or Team Name

  • Renal Medicine of Kolling Institute

Kidney fibrosis, the final common pathway of various forms of chronic kidney disease (CKD), affects 10% of the world’s population. However, the efficiency of current therapies is limited. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a potential therapeutic target for tissue fibrosis. To date, the only approved CXCR4 antagonist (AMD3100) was terminated due to its off-target cardiotoxicity. Recently we have developed a fully human single-domain antibody-like scaffold termed i-body AD-114 with specific high binding affinity to CXCR4. AD-114 selectively blocks CXCR4 signaling and has shown anti-fibrotic effects in pulmonary fibrosis. The present studies have demonstrated the renoprotection of AD-114 in kidney fibrosis.


CXCR4 expression in the kidney biopsies from patients with diabetic kidney disease (DKD) and kidneys from three mouse models of CKD was detected using immunohistochemistry (IHC). To determine the preventive role of AD-114 in the development of CKD, a mouse model of folic acid (FA)-induced nephropathy was used. C57/BL6 mice (6-8 weeks, N = 10) were challenged with 250 mg/kg of FA followed by daily administration of AD-114(10 mg/kg) intraperitoneally for 21 day. Nonspecific i-body that doesn't bind CXCR4(10 mg/kg) and AMD3100(10 mg/kg) served as negative and positive controls. To assess the therapeutic role, i-body administration commenced when renal injury was established at Day 8 of FA injection and continued for 14 days. Renal function, histology and ECM deposition were assessed by urine creatinine/albumin kits, IHC and Masson’s trichrome staining.


CXCR4 expression was significantly upregulated in patients with DKD and fibrotic kidneys of three mouse models of CKD compared to control groups (P<0.001, N=6). In both prophylactic and therapeutic models, the results showed AD-114 markedly ameliorated renal function impairment (24h urine albumin/creatinine ratio) and fibrotic kidney remodeling (Masson’s trichrome staining) and attenuated the FA-induced overexpression of collagen-4 (COL-4), fibronectin (FN), collagen-1(COL-1), collagen-3 (COL-3) and α-SMA (IHC) in kidneys compared to negative control i-body.


AD-114 effectively ameliorated fibrotic kidney remodeling through targeting CXCR4 signaling in a murine model of kidney fibrosis.


  • Government Support - Non-U.S.