Renal tubule injury: a driving force toward chronic kidney disease

Kidney Int. 2018 Mar;93(3):568-579. doi: 10.1016/j.kint.2017.09.033. Epub 2018 Jan 17.


Renal tubules are the major component of the kidney and are vulnerable to a variety of injuries including hypoxia, proteinuria, toxins, metabolic disorders, and senescence. It has long been believed that tubules are the victim of injury. In this review, we shift this concept to renal tubules as a driving force in the progression of kidney diseases. In response to injury, tubular epithelial cells undergo changes and function as inflammatory and fibrogenic cells, with the consequent production of various bioactive molecules that drive interstitial inflammation and fibrosis. Innate immune-sensing receptors on the tubular epithelium also aggravate immune responses. Necroinflammation, an autoamplification loop between tubular cell death and interstitial inflammation, leads to the exacerbation of renal injury. Furthermore, tubular cells also play an active role in progressive renal injury via emerging mechanisms associated with a partial epithelial-mesenchymal transition, cell-cycle arrest at both G1/S and G2/M check points, and metabolic disorder. Thus, a better understanding the mechanisms by which tubular injury drives inflammation and fibrosis is necessary for the development of therapeutics to halt the progression of chronic kidney disease.

Keywords: acute kidney injury; chronic kidney disease; renal fibrosis; renal inflammation; renal tubule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury / complications*
  • Acute Kidney Injury / immunology
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Progression
  • Energy Metabolism
  • Epithelial Cells* / immunology
  • Epithelial Cells* / metabolism
  • Epithelial Cells* / pathology
  • Epithelial-Mesenchymal Transition
  • Fibrosis
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Kidney Tubules* / immunology
  • Kidney Tubules* / metabolism
  • Kidney Tubules* / pathology
  • Renal Insufficiency, Chronic / etiology*
  • Renal Insufficiency, Chronic / immunology
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology
  • Signal Transduction


  • Cell Cycle Proteins
  • Cytokines
  • Inflammation Mediators