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  • Review Article
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The epidermal growth factor receptor pathway in chronic kidney diseases

Key Points

  • The epidermal growth factor receptor (EGFR) pathway has a crucial role in renal physiology, development, tissue repair and electrolyte handling

  • Experimental studies have provided convincing evidence that dysregulated EGFR signalling is involved in many chronic kidney diseases

  • Interventions in the EGFR pathway have been shown to improve renal outcomes in various models of chronic kidney disease (CKD)

  • Nonspecific interventions in the EGFR pathway might lead to a number of systemic adverse effects, as demonstrated in clinical trials in the field of oncology

  • A targeted approach might limit these adverse effects but still inhibit renal fibrosis, and might serve as a treatment strategy for patients with CKD

Abstract

The epidermal growth factor receptor (EGFR) pathway has a critical role in renal development, tissue repair and electrolyte handling. Numerous studies have reported an association between dysregulation of this pathway and the initiation and progression of various chronic kidney diseases such as diabetic nephropathy, chronic allograft nephropathy and polycystic kidney disease through the promotion of renal cell proliferation, fibrosis and inflammation. In the oncological setting, compounds that target the EGFR pathway are already in clinical use or have been evaluated in clinical trials; in the renal setting, therapeutic interventions targeting this pathway by decreasing ligand availability with disintegrin and metalloproteinase inhibitors or with ligand-neutralizing antibodies, or by inhibiting receptor activation with tyrosine kinase inhibitors or monoclonal antibodies are only just starting to be explored in animal models of chronic kidney disease and in patients with autosomal dominant polycystic kidney disease. In this Review we focus on the role of the EGFR signalling pathway in the kidney under physiological conditions and during the pathophysiology of chronic kidney diseases and explore the clinical potential of interventions in this pathway to treat chronic renal diseases.

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Figure 1: Specificity of the various epidermal growth factor (EGF) receptor ligands for the four known ErbB receptors.
Figure 2: Three distinct mechanisms of activation of the epidermal growth factor receptor (EGFR) pathway.
Figure 3: Localization of ErbB receptors and ligands within the nephron.
Figure 4: Potential targets for medical intervention in the EGFR pathway.
Figure 5: Cross sections of kidneys from a rat model of polycystic kidney disease (cy/+ Han:SPRD).

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Harskamp, L., Gansevoort, R., van Goor, H. et al. The epidermal growth factor receptor pathway in chronic kidney diseases. Nat Rev Nephrol 12, 496–506 (2016). https://doi.org/10.1038/nrneph.2016.91

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